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Results - Drug Class Review: Pegylated Interferons for Chronic Hepatitis C Infection - NCBI Bookshelf
ResultsOverviewFigure 1 shows the flow of studies. Literature searches identified 829 citations, and 166 of these were potentially relevant. After review of the full text of these 166, we included 86 studies: 41 reports of randomized controlled trials (in 46 publications),33–78 five systematic reviews (in 6 publications),9, 13–15, 79, 80 and 40 uncontrolled studies that provided information on adverse events.81–120 Excluded studies are listed in Appendix C.
Figure 1Results of literature search. Among the 41 included randomized controlled trials, two were short-term head-to-head trials of dual therapy with pegylated interferon alfa-2a versus dual therapy with pegylated interferon alfa-2b,71, 72 15 trials compared pegylated interferon plus ribavirin to non-pegylated interferon plus ribavirin,34, 35, 40, 43–46, 58, 59, 61, 63, 68, 70, 73, 74 and five compared dual therapy with pegylated interferon plus ribavirin to pegylated interferon monotherapy (Evidence Table 1).42, 48, 53, 56, 57 Nineteen trials compared different doses or treatment durations of the same peginterferon (Evidence Table 2).33, 37, 39, 41, 47, 49, 50, 54, 55, 60, 62–64, 67, 69, 75–78 Two trials directly compared different doses of ribavirin as part of dual therapy with pegylated interferon.50, 52 Two trials were included in more than one category.50, 63One head-to-head trial available as an abstract was excluded because it only reported interim (8-week) results of a short-term (12 weeks) trial.121 We identified six other unpublished trials from pharmaceutical company dossiers that otherwise met inclusion criteria (Appendix D). These trials were not included in our primary analyses, but results were considered in sensitivity analyses in order to determine how they affected conclusions. A large (N=4913) trial compared weight-based to fixed, lower-dose ribavirin in patients on dual therapy with pegylated interferon alfa-2b.122 The other five trials evaluated effects of different doses or duration of therapy123–126 or compared effects of therapy in different racial groups.127Overview of methodological quality of included trialsDetails of our quality assessment of included randomized controlled trials are shown in Evidence Table 3. Two of 41 included trials were rated good quality, 9 were rated poor, and the rest were fair (Table 4). Fourteen of 41 trials (34.1%) described adequate randomization methods, 39% described adequate allocation concealment, 12.2% masked patients and providers, 12.2% masked outcome assessors, and 85.4% reported ITT results.Table 4Summary of quality assessment of included published trials. Key Question 1. What is the comparative effectiveness of regimens of peginterferon alfa-2a plus ribavirin versus peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C virus infection?Summary of evidenceWe found insufficient evidence to determine if dual therapy with pegylated interferon alfa-2a is superior to dual therapy with pegylated interferon alfa-2b for achieving SVR or SBR. Head-to-head trials data were sparse (two trials), short-term (8 to 12 weeks), clinically diverse, and had methodological flaws. Indirect analysis of trials comparing dual therapy with pegylated interferon alfa-2a or alfa-2b to a common comparator (dual therapy with non-pegylated interferon) indicate no significant differences in rates of SVR, though interpretation of findings is limited by clinical diversity across trials and imprecise estimates of effects. There are also no clear differences in SBR. Data on histologic outcomes and quality of life are sparse and there are no comparative data on other outcomes such as cirrhosis, hepatocellular cancer, liver transplant, or functional status.Effectiveness versus efficacyWe considered all of the trials included in this report efficacy studies, as they generally applied numerous inclusion criteria, were conducted in specialty settings, used rigid dosing regimens, and evaluated relatively short-term, intermediate outcomes (SVR and SBR rates).128Systematic reviewsWe identified five systematic reviews (reported in six publications) on efficacy of dual therapy with pegylated interferon.9, 13–15, 79, 80 All of the systematic reviews included the same two published trials (one evaluating dual therapy with pegylated interferon alfa-2a48 and the other pegylated interferon alfa-2b63). In both trials, dual therapy with pegylated interferon was compared to dual therapy with non-pegylated interferon or monotherapy with pegylated interferon. We excluded four of the systematic reviews because they did not assess comparative efficacy of dual pegylated interferon regimens and are missing new, relevant trials.9, 13–15, 79 The fifth systematic review focused on efficacy of dual therapy with pegylated interferon in patients with HCV genotype 4 infection and is reviewed for key question 3.79Head-to-head trialsTwo head-to-head trials compared dual therapy with pegylated interferon alfa-2a versus pegylated interferon alfa-2b.71, 72 Both were short-term (eight to twelve weeks) efficacy trials that only assessed end-of-treatment virologic responses. Results of the two trials cannot be directly compared or combined because of differences in study quality, patient populations, and interventions (Table 5). One trial (rated fair-quality), sponsored by the manufacturer of pegylated interferon alfa-2b, only included treatment-naïve patients infected with HCV genotype 1 and initially placed patients on four weeks of pegylated interferon monotherapy before ribavirin was added for the last four weeks.71 The other trial, sponsored by the manufacturer of pegylated interferon alfa-2a, was rated poor quality (flaws include allocating consecutive patients to alternating therapy), did not restrict to genotype 1, initiated patients on dual therapy, and included treatment-experienced patients (30% of enrolled population).72 In both trials, end-of- treatment virologic response was defined as >=2.0 log10 decrease in HCV load.Table 5Head-to-head trials of dual therapy with pegylated interferon alfa-2a vs. dual therapy with pegylated interferon alfa-2b. In the fair-quality trial, there was no significant difference (p=0.09) in 8-week virologic response rates between dual therapy with pegylated interferon alfa-2a (44% or 8/18) and dual therapy with pegylated interferon alfa-2b (72% or 13/18) (Table 5).71 In the poor-quality trial, there was also no difference in 12-week virologic response rates, though the trend was in the opposite direction (83% or 48/58 for pegylated interferon alfa-2a versus 67% or 39/58 for pegylated interferon alfa-2b, p=0.08).72 In a subgroup analysis of treatment-naïve patients in this trial, the same trend was observed (90% vs. 75%, p=0.61). Biochemical, histological, and clinical outcomes were not reported in either trial.A third short-term (12 weeks) head-to-head trial was excluded because only interim results have been reported in a conference abstract.121 It found no significant difference in rates of virologic response through eight weeks of dual therapy with pegylated interferon alfa-2a versus pegylated interferon alfa-2b (66% or 29/44 versus 50% or 22/44). Results of a large (expected enrollment 2,880), head-to-head trial of 48-week dual pegylated interferon regimens in patients with HCV genotype 1 infection (the IDEAL study) are not yet available, but expected later in 2007.129 This trial is sponsored by the manufacturer of pegylated interferon alfa-2b.Active-controlled trialsDual therapy with pegylated interferon versus dual therapy with non-pegylated interferonActive-controlled trials of dual therapy with pegylated interferon alfa-2a and pegylated interferon alfa-2b against a common comparator could provide indirect evidence on comparative effectiveness. We identified five trials comparing dual therapy with pegylated interferon alfa-2a plus ribavirin versus dual therapy with non-pegylated interferon alfa-2a plus ribavirin35, 44, 61, 73 or dual therapy with non-pegylated interferon alfa-2b plus ribavirin48 and 11 trials comparing dual therapy with pegylated interferon alfa-2b plus ribavirin versus dual therapy with non-pegylated interferon alfa-2b plus ribavirin.34, 40, 43, 45, 46, 58, 59, 63, 68, 70, 74 One trial was rated good-quality,73 three trials poor-quality,35, 46, 68 and the remainder fair-quality. Sample sizes ranged from 2135 to 153063 enrollees. Common methodological shortcomings observed in the trials were inadequate description of randomization and allocation concealment methods and open-label design. All trials of pegylated interferon alfa-2a evaluated a dose of 180 μg /kg once weekly. Seven trials of pegylated interferon alfa-2b evaluated a dose of 1.5 μg/kg once weekly,43, 45, 46, 59, 63, 70, 74 and the other four34, 40, 58, 68 evaluated a range of different doses (Table 6). Ribavirin doses varied in both sets of trials, ranging from 600 to 1600 mg daily. In one trial, patients randomized to dual therapy with pegylated interferon and non-pegylated interferon also received amantadine.61Table 6Characteristics of trials comparing dual therapy with pegylated interferon to dual therapy with non-pegylated interferon. Three of the pegylated interferon alfa-2a35, 44, 73 and four of the pegylated interferon alfa-2b trials43, 45, 58, 68 evaluated HIV co-infected patients. Two trials did not specify whether patients had previously been exposed to interferon therapy.35, 68 The other trials evaluated only treatment-naïve patients. Three trials focused exclusively46, 47 or primarily34 on patients with HCV genotype 4 infection and three trials40, 70, 74 evaluated only patients with HCV genotype 1 infection. The proportion of patients with HCV genotype 1 ranged from 44% to 78% in the other trials. All trials required patients to have liver biopsy findings consistent with HCV infection and at least mild inflammation or fibrosis for enrollment. Only one trial specifically included patients with normal transaminases.77 Three trials (all evaluating HIV co-infected patients)43, 44, 68 did not use transaminase elevations as an eligibility criterion. In all other trials, transaminase elevation was required for enrollment. No trial included patients with decompensated cirrhosis. Rates of SVR ranged from 27% to 65% on dual therapy with pegylated interferon alfa-2a, and from 27% to 67% on dual therapy with pegylated interferon alfa-2b, with the exception of one poor-quality, non-randomized trial68 of HIV co-infected patients that reported an SVR of 5% (1/20).No trial was designed to evaluate rates of cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, or liver transplant. Only one trial48 reported effects on quality of life.51All trials reported rates of SVR. In pooled analysis, dual therapy with pegylated interferon alfa-2a plus ribavirin was superior to non-pegylated interferon alfa-2a or alfa-2b plus ribavirin (five trials, RR 2.14, 95% CI 1.32 to 3.47) (Figure 2). There was a significant difference between estimates based on the subgroup of four trials (N=969)35, 44, 61, 73 comparing dual therapy with pegylated interferon alfa-2a to dual therapy with non-pegylated interferon alfa-2a (RR 2.55, 95% CI 1.75 to 3.74) and the single, large (N=897) trial48 comparing dual therapy with pegylated interferon alfa-2a to dual therapy with non-pegylated interferon alfa-2b (RR 1.28, 95% CI 1.12 to 1.46; p=0.038 for difference).
Figure 2Forest plot on sustained virologic response, dual therapy with pegylated interferon alfa-2a versus dual therapy with non-pegylated interferon alfa-2a or alfa-2b. Pegylated interferon alfa-2b plus ribavirin was also superior to non-pegylated interferon alfa-2b plus ribavirin for achieving an SVR (11 trials, RR 1.28, 95% CI 1.10 to 1.49) (Figure 3).
Figure 3Forest plot on sustained virologic response, dual therapy with pegylated interferon alfa-2b versus dual therapy with non-pegylated interferon. Excluding trials of HIV-infected patients attenuated the difference in pooled estimates between dual therapy with pegylated interferon alfa-2a (2 trials, RR 1.55, 95% CI 1.02 to 2.36, see Figure 2) and dual therapy with pegylated interferon alfa-2b (7 trials, RR 1.12, 95% CI 1.03 to 1.23, see Figure 3), and decreased heterogeneity in the pegylated interferon alfa-2a trials. Some of the remaining heterogeneity in the two trials of pegylated interferon alfa-2a in patients without HIV co-infection may be related to the addition of amantadine to both treatment arms in one of the trials.61 Estimates were stable after excluding poor-quality trials or trials evaluating only patients with genotype 1 or genotype 4 infection. Estimates were also stable after excluding results of patients randomized to lower-dose pegylated interferon alfa-2b from a trial that evaluated lower (0.5 μg /kg/wk) and higher (1.5 μg/kg/wk) dose dual therapy.63We performed an adjusted indirect analysis to evaluate relative efficacy of dual therapy with pegylated interferon alfa-2a versus dual therapy with pegylated interferon alfa-2b on rates of SVR, based on trials in which each was compared to dual therapy with non-pegylated interferon. However, results of the indirect analysis should be interpreted with caution. Although indirect meta-analyses usually agree with direct meta-analyses of head-to-head trials, results can be discordant or contradictory if the critical assumption that treatment effects are consistent across all the trials is violated.25, 27, 28 This can occur when there are methodological flaws in the studies or differences in patient populations, interventions, or other factors. In this set of trials, substantial clinical diversity was observed in patient populations, dosing of interventions (both for pegylated interferon and for ribavirin), and comparator treatments (interferon alfa-2a versus interferon alfa-2b). In addition, confidence intervals for our estimates are wide, due to a relatively small data set and decreased precision of indirect compared to direct analyses.Including all trials, adjusted indirect analysis (Table 7) found no significant differences (and wide confidence intervals) in efficacy for SVR between dual therapy with pegylated interferon alfa-2a versus dual therapy with pegylated interferon alfa-2b, using dual therapy with non-pegylated interferon alfa-2a or alfa-2b as the common comparator (RR 1.67, 95% CI 0.56 to 5.04). Because comparing dual therapy with pegylated interferon to dual therapy with different non-pegylated interferons (alfa-2a or alfa-2b) could violate assumptions about relative treatment effects across both sets of trials, we also performed the indirect analysis using only trials that compared dual therapy with pegylated interferon to dual therapy with non-pegylated interferon alfa-2b. This analysis found no difference in the point estimate of relative efficacy (RR 1.00, 95% CI 0.47 to 2.11). We did not perform an adjusted indirect analysis for the subgroup of trials in non-HIV infected persons, as confidence intervals for estimates of relative risk for SVR from the direct analyses overlapped substantially and the number of available trials was small.Table 7Adjusted indirect analysis for sustained virologic response rates. Seven trials reported rates of SBR. One trial found dual therapy with pegylated interferon alfa-2a superior to dual therapy with non-pegylated interferon alfa-2a, each in combination with amantadine (RR 1.98, 95% CI 1.49 to 2.63).61 The six other trials evaluated dual therapy with pegylated interferon alfa-2b versus dual therapy with non-pegylated alfa-2b.34, 40, 58, 59, 70, 74 There was no difference in pooled risk of SBR (RR 1.17, 95% CI 0.98 to 1.40) (Figure 4). There were too few trials reporting SBR to perform indirect meta-analysis.
Figure 4Forest plot on sustained biochemical response, dual therapy with pegylated interferon alfa-2b versus dual therapy with non-pegylated interferon alfa-2b. The three trials that evaluated histologic outcomes found no differences between dual therapy with pegylated interferon alfa-2b and dual therapy with non-pegylated interferon alfa-2b in liver biopsy scores for fibrosis or inflammation.43, 59, 63 The one trial reporting health-related quality of life and fatigue severity scores in patients randomized to different treatments (as opposed to responders versus non-responders) found dual therapy with pegylated interferon alfa-2a to be associated with improved scores in a variety of domains during therapy compared to dual therapy with non-pegylated interferon alfa-2b. Yet differences were small (generally less than 5 points on 100 point scales) and scores had returned to baseline values or better in both groups 24 weeks after the end of treatment.48, 51 In addition, patients in this trial were aware of their virologic response to therapy, which could have affected assessments of health-related quality of life.The funnel plot for the eleven trials of dual therapy with pegylated interferon alfa-2b versus dual therapy with non-pegylated interferon alfa-2b for SVR is difficult to interpret because of a small outlier trial.68 However, after excluding this trial, no funnel plot asymmetry was apparent.Dual therapy with pegylated interferon versus pegylated interferon monotherapyWe identified six trials of dual therapy with pegylated interferon (5 trials evaluating pegylated interferon alfa-2a48, 53, 56, 57, 73 and one trial evaluating pegylated interferon alfa-2b42) versus pegylated interferon monotherapy. One trial was rated good-quality,73 one poor-quality,56 and the remainder fair-quality. The number of patients randomized to pegylated interferon monotherapy or dual therapy ranged from 2053 to 89748 enrollees. Two trials42, 57 evaluated HIV co-infected patients and one53 evaluated thalassemic patients. The proportion of patients with HCV genotype 1 infection ranged from 44% to 86%. All trials only evaluated treatment-naïve patients. Rates of SVR for dual therapy ranged from 33% to 57% with pegylated interferon alfa-2a, with the exception of one trial57 that reported an SVR of 5%. This trial only randomized HIV co-infected patients who failed to respond to 14 weeks of initial pegylated interferon monotherapy. The single trial of dual therapy with pegylated interferon alfa-2b evaluated HIV co-infected patients and reported an SVR of 22%.42The pooled relative risk for an SVR in patients randomized to dual therapy with pegylated interferon alfa-2a versus pegylated interferon alfa-2a monotherapy was 1.92 (5 trials, 95% CI 1.63 to 2.26) (Figure 5). Excluding either the small (N=20) trial53 of thalassemic patients or the trial of HIV-infected non-responders57 yielded similar estimates (RR 1.92, 95% CI 1.63 to 2.27 and RR 1.91, 95% CI 1.62 to 2.28, respectively). The small (N=56) trial of dual therapy with pegylated interferon alfa-2b versus pegylated interferon alfa-2b monotherapy reported an RR for SVR of 2.39 (95% CI 0.99 to 5.79).42 We did not attempt an indirect analysis because estimates of SVR for dual versus monotherapy overlapped and there was only one trial of dual therapy with pegylated interferon alfa-2b. One trial found that patients randomized to dual therapy with pegylated interferon alfa-2a plus ribavirin experienced greater declines in health-related quality of life and fatigue severity scores during treatment compared to those randomized to pegylated interferon alfa-2a monotherapy.48, 51 No trial reported SBR, histologic outcomes, or other clinical outcomes.
Figure 5Forest plot on sustained virologic response, dual therapy with pegylated interferon alfa-2a versus pegylated interferon alfa-2a monotherapy. Observational studies of long-term clinical outcomesWe identified no observational studies evaluating long-term clinical outcomes such as cirrhosis, hepatocellular cancer, need for liver transplant, or mortality.Key Question 1a. How does duration of treatment or dosing protocols (including weight-based or maintenance dosing or dosing of ribovirin) affect estimates of comparative effectiveness?SummaryPublished trials directly comparing different doses of pegylated interferon as part of dual therapy are only available for pegylated interferon alfa-2b. No dose has been shown to be more effective than 1.5 μg/kg/week for achieving an SVR. The optimal dose of pegylated interferon alfa-2b as part of dual therapy in non-responders or relapsers is unclear.Trials directly comparing different durations of therapy are characterized by substantial clinical diversity. In general, in patients with HCV genotype 1 infection, 48 weeks of dual therapy with pegylated interferon appears to be more effective than shorter courses. On the other hand, in patients with HCV genotype 2 or 3 infection, shorter courses appear equally effective compared to a 48 week course, particularly in early responders to therapy, in whom a 12 week-course of therapy appears as effective as 24 weeks.Studies evaluating effects of dose and duration are of limited value for evaluating comparative effectiveness of dual therapy with pegylated interferon alfa-2a versus pegylated interferon alfa-2b because none directly compared effects of duration or dose between the two regimens. Pooling trials or performing meta-regression was not possible because of substantial clinical diversity across trials in patient populations, dosing of drugs, and/or duration of therapy.Overview of trials on dose or durationUnderstanding effects of dose and duration on efficacy of dual therapy with pegylated interferon would be very helpful for selecting optimal treatment regimens and interpreting results of clinical trials. We included 19 trials on efficacy of dual therapy with pegylated interferon at different doses, varying duration, or with standardized versus tailored (to early response) treatment.33, 37, 39, 41, 47, 49, 50, 52, 54, 55, 60, 62, 64, 67, 69, 75–78 None of the 19 trials directly compared dual therapy regimens of pegylated interferon alfa-2a versus pegylated interferon alfa-2b. Two trials directly compared different doses of ribavirin as part of dual therapy with pegylated interferon.50, 52 We did not pool trial results or perform meta-regression because of differences in study populations, doses of pegylated interferon, doses of ribavirin, and/or duration of therapy. Because of this clinical diversity, the indirect evidence from this set of trials is of limited value for evaluating comparative effectiveness of dual therapy with pegylated interferon alfa-2a versus pegylated interferon alfa-2b.Dose of pegylated interferonAll eight dose-ranging trials evaluated pegylated interferon alfa-2b (Table 8).33, 41, 49, 54, 60, 63, 64, 67 No trial evaluated standardized versus weight-based dosing.Table 8Trials evaluating efficacy of different doses in regimens of dual therapy with pegylated interferon alfa-2b. In treatment-naïve patients, one large (N=1,025), fair-quality trial found a dose of 0.5 μg/kg/week inferior to 1.5 μg/kg/week for achieving an SVR (47% vs. 54%, p=0.01).63 Benefits of the higher dose were only observed in the subgroup of patients with genotype 1 infection (42% vs. 34%). Three smaller, fair-quality trials found no differences in SVR between 0.5 μg/kg/week verses 1.0 μg/kg/week,41 1.0 μg/kg/week versus 1.5 μg/kg/week,67 or 0.75 μg/kg/week versus 1.5 μg/kg/week of pegylated interferon alfa-2b,33 each in combination with ribavirin 800 mg/day. The latter trial33 evaluated patients with severe fibrosis (METAVIR fibrosis stage F3 or F4) and the other two trials evaluated patients with less severe biopsy findings. A poor quality trial found both 0.7 μg/kg/week and 1.4 μg/kg/week doses superior to 0.35 μg/kg/week, at varying ribavirin doses.49 Three trials of relapsers or non-responders to prior interferon-based therapy (two fair-quality, one poor-quality) found no significant differences in SVR rates between higher and lower-dose regimens of peginterferon alfa-2b, though trends favored the higher-dose regimen in each trial.54, 60, 64 However, each trial evaluated a different dose comparison.Two unpublished trials compared efficacy of different doses of pegylated interferon alfa-2a as part of combination therapy. One small (N=40) trial found no clear difference in rates of SVR between patients randomized to a dose of 180 μg/week versus those randomized to 270 μg/week (70% vs. 79%, p not reported).123 The second trial compared dual therapy using higher induction doses of pegylated interferon alfa-2a compared to standard dosing in patients without an early virologic response.124 In addition, this trial evaluated effects of different durations of therapy, however final results are not yet available.DurationWe identified nine trials evaluating effects of duration of dual therapy with pegylated interferon plus ribavirin on SVR rates (Table 9).37, 39, 47, 50, 55, 69, 75–77 The only good-quality trial found 48 weeks of dual therapy with pegylated interferon alfa-2a plus ribavirin more effective than 24 weeks of therapy for achieving SVR (OR 1.53, 95% CI 1.17 to 2.01).50 In subgroup analyses, 48 weeks of therapy was superior to 24 weeks only in patients with genotype 1 infection (OR 2.19, 95% CI 1.52 to 3.16, compared to OR 0.89, 95% CI 0.56 to 1.42 with genotypes 2 or 3). A fair-quality trial also found 48 weeks superior to 24 weeks in patients with normal transaminases, with benefits limited to the subgroup of genotype 1-infected patients.77Table 9Trials evaluating efficacy of different durations of dual therapy with pegylated interferon. Five other trials (all rated fair-quality) also evaluated effect of treatment duration, but limited enrollment to patients with specific HCV genotypes.37, 47, 55, 75, 76 In patients with HCV genotype 1 infection, two trials found 48 weeks of dual therapy with pegylated interferon alfa-2a39 or alfa-2b76 superior to 24 weeks for achieving an SVR (80% vs. 49%, p<0.0576 and 48% vs. 28%, p=0.017539). A third trial found no difference between 72 and 48 weeks of dual therapy with pegylated interferon alfa-2a.37 In this trial, however, the subgroup of patients who were "slow responders" (defined as HCV-positive at week 12 but negative at week 24) had a better sustained viral response with 72 weeks versus 48 weeks of treatment (29% vs. 17%, P=0.04). In patients with HCV genotypes 2 or 3, one trial found 16 weeks of dual therapy with pegylated interferon alfa-2a as effective for achieving an SVR as 24 weeks in patients with an early (six week) response to treatment.75 In patients with HCV genotype 4, results from two trials were inconsistent, with one trial finding 36 or 48 weeks of dual therapy with pegylated interferon superior to 24 weeks,55 but no differences between 24 and 48 weeks in the second trial.47Longer courses of dual therapy with pegylated interferon therapy could be more effective in patients who do not respond to treatment within the first four to six weeks. One fair-quality trial found 72 weeks of dual therapy with pegylated interferon alfa-2a superior to 48 weeks for achieving SVR in early non-responders.69 An alternative to using a fixed interferon regimen is to individualize the dose or duration of therapy based on an individual's early virologic response to treatment. One trial found that in patients with HCV genotype 2 or 3 infection, shortening the duration of therapy from 24 to 12 weeks in patients who cleared their virus by week 4 was as effective as treating all patients for 24 weeks.62 A second trial found no differences between a standardized 48 week regimen and individualized therapy based on a more complicated protocol for classifying early response and modifying treatment.78Two trials currently available only as abstracts evaluated effects of duration on efficacy of dual therapy with pegylated interferon alfa-2a. One trial found 16 weeks inferior to 24 weeks for achieving SVR in patients with HCV genotype 2 or 3 infection (66% vs. 74%, p<0.005).126 Unlike other trials evaluating less than 24 weeks of therapy, it was not limited or tailored to patients with an early virologic response. Another trial (N=377) found no difference between 24 and 48 weeks of dual therapy with pegylated interferon plus ribavirin 800 mg (28% vs. 26%) in patients with genotype 1 infection and compensated cirrhosis, though the longer course appeared superior in patients randomized to ribavirin 1000 to 1200 mg (37% vs. 26%, p not reported).125 There was no difference in patients with non-genotype 1 infection.Dose of ribavirinDifferent ribavirin dosing schemes could influence efficacy of dual therapy regimens, but have only been directly evaluated in two trials.50,52 One trial found dual therapy with pegylated interferon alfa-2a in combination with higher dose ribavirin (1000 to 1200 mg, depending on weight) more effective than dual therapy with lower dose ribavirin (800 mg) for achieving SVR in the subgroup of patients with genotype 1 infection (OR 1.55, 95% CI 1.14 to 2.10), but not in those with genotype 2 or 3 infection (OR 1.00, 95% CI 0.63 to 1.61).50 A second trial also found dual therapy with pegylated interferon alfa-2a in combination with higher dose ribavirin more effective than lower dose ribavirin in patients with advanced fibrosis or cirrhosis.52 However, in contrast to the other trial, higher dose ribavirin (1000 to 1200 mg) was superior to lower dose ribavirin (600 to 800 mg) for SVR (72% vs. 45%, p=0.03) in patients with genotype 2 or 3 infection, but not in patients with genotype 1 or 4 infection (SVR 32% vs. 32%). In two other published trials, patients were randomized to different doses of ribavirin, but pegylated interferon doses also varied, making it difficult to determine dose effects of the individual drugs.49, 54A large (N=4,913, 62% HCV genotype 1) trial available only as an abstract found pegylated interferon alfa-2b modestly more effective combined with higher, weight-based dosing of ribavirin (800 to 1400 mg) than when combined with fixed-dose, 800 mg ribavirin (SVR 44% vs. 41%, p=0.02).130 A second trial published only as an abstract found 48 weeks of pegylated interferon alfa-2a more effective in combination with weight-based dosing of ribavirin (1000 to 1200 mg) than with fixed-dosing (800 mg) in patients with genotype 1 infection and compensated cirrhosis.125 In this same trial, the ribavirin dosing regimen was associated with no differences in rates of SVR in patients with non-genotype 1 infection or in those randomized to 24 weeks of therapy.Effects of duration or dose on adverse eventsWe found no consistent pattern showing an association between longer duration or higher doses of dual therapy with pegylated interferon and increased rates of withdrawal due to adverse events (Tables 8 and 9). Other adverse events were reported inconsistently.Key Question 2. What is the comparative tolerability and safety of peginterferon alfa-2a plus ribavirin versus peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C virus infection?SummaryWe found insufficient evidence to determine if dual therapy with one pegylated interferon is safer than dual therapy with the other pegylated interferon. Data from head-to-head trials are extremely sparse (one short-term trial) and inadequate for judging comparative safety. Indirect analysis of trials comparing dual therapy with pegylated interferon alfa-2a or alfa-2b to dual therapy with non-pegylated interferon show no significant differences in rates of withdrawal due to adverse events or other adverse events, but interpretation of findings is limited by clinical diversity across trials, imprecise estimates of effects, and inconsistent reporting of adverse events. Observational studies were almost all uncontrolled and provided no additional useful information on comparative safety, as rates of withdrawal due to adverse events on dual therapy ranged widely across trials for the same pegylated interferon and overlapped for therapy based on each of the two pegylated interferons.Systematic reviewsOne systematic review included two large, pivotal trials that reported similar rates of withdrawal due to adverse events in patients randomized to dual therapy with pegylated interferon plus ribavirin versus dual therapy with non-pegylated interferon plus ribavirin (10% vs. 11% in one trial of dual therapy with pegylated interferon alfa-2a48 and 14% vs. 13% in one trial of pegylated interferon alfa-2b63).13 It did not evaluate other adverse events.Head-to-head trialsOne small, short-term, fair-quality randomized trial found no differences between dual therapy with pegylated interferon alfa-2a and pegylated interferon alfa-2b in withdrawals due to adverse events (11% or 2/18 vs. 22% or 4/18), flu-like symptoms (17% or 3/18 vs. 28% or 5/18), or the proportion of patients with anemia or leukopenia.71 The only other head-to-head trial did not report adverse events or withdrawals due to adverse events.72Active-controlled trialsDual therapy with pegylated interferon versus dual therapy with non-pegylated interferonAdverse events reported in randomized controlled trials are shown in Evidence Table 4 (randomized controlled trials of efficacy) and Evidence Table 5 (dose- or duration-ranging trials). Eleven trials reported rates of withdrawal due to adverse events in patients randomized to dual therapy with pegylated interferon versus dual therapy with non-pegylated interferon.34, 35, 40, 43–46, 48, 58, 63, 73 Six deaths were reported during therapy in patients randomized to dual therapy with pegylated interferon,43, 59 five of which occurred in HIV co-infected patients.43 Rates of withdrawal due to adverse events on dual therapy with pegylated interferon ranged from 6% to 16%.In pooled analyses, there was no significant difference in rates of withdrawal due to adverse events for dual therapy with pegylated interferon alfa-2a versus dual therapy with non-pegylated interferon (4 trials, RR 0.80, 95% CI 0.60 to 1.07, Figure 6) or dual therapy with pegylated interferon alfa-2b versus dual therapy with non-pegylated interferon (7 trials, RR 0.94, 95% CI 0.68 to 1.31, Figure 7). Other adverse events were less consistently reported. Compared to dual therapy with non-pegylated interferon, dual therapy with pegylated interferon alfa-2a (one trial, RR 2.33, 95% CI 1.64 to 3.33) and dual therapy with pegylated interferon alfa-2b (four trials, RR 2.58, 955 CI 1.52 to 4.37) were associated with similarly increased risks for neutropenia. A similar trend was observed for risk of anemia. There were no significant differences between dual therapy with pegylated interferon alfa-2a or alfa-2b and dual therapy with non-pegylated interferon in rates of depression or flu-like symptoms.
Figure 6Forest plot on withdrawal due to adverse events, dual therapy with pegylated interferon alfa-2a versus dual therapy with non-pegylated interferon alfa-2a or -2b. Figure 7Forest plot on withdrawal due to adverse events, dual therapy with pegylated interferon alfa-2b versus dual therapy with non-pegylated interferon alfa-2b. Dual therapy with pegylated interferon versus pegylated interferon monotherapyThree of six trials reported rates of withdrawal due to adverse events in patients randomized to dual therapy with pegylated interferon versus patients randomized to pegylated interferon monotherapy. Two trials evaluated pegylated interferon alfa-2a48, 73 and the third evaluated pegylated interferon alfa-2b.42 No deaths were reported in patients randomized to dual therapy. Rates of withdrawal due to adverse events on dual therapy ranged from 6% to 12% and were very similar between dual therapy and monotherapy in all three trials (RR 1.07, 95% CI 0.74 to 1.53). There were also no clear differences in rates of depression or in hematologic side effects (each reported by three trials).In the pegylated interferon alfa-2b trial, rates of flu-like symptoms were higher in patients randomized to dual therapy versus those randomized to pegylated interferon monotherapy (22% vs. 3%).42 However, the 3% rate of flu-like symptoms associated with pegylated interferon monotherapy appears unusually low.Adverse events reported in uncontrolled studiesForty uncontrolled or observational studies provided information about adverse events associated with dual therapy with pegylated interferon (Evidence Table 6).81–120In one study that enrolled patients taking either pegylated interferon alfa-2a or alfa-2b, the type of pegylated interferon was not associated with discontinuation (rates not reported).88 Nine other studies included patients receiving dual therapy with pegylated interferon alfa-2a90, 91, 95, 96, 98, 99, 113, 114, 116 and 31 included patients receiving dual therapy with pegylated interferon alfa-2b.81–89, 92–94, 97, 100–112, 115, 117–120 Six studies were designed to measure specific adverse events, including depression,87, 109 psychiatric side effects,97 infections,96 weight loss,112 and ocular changes.89Eleven studies, all of dual therapy with pegylated interferon alfa-2b, included patients with HIV co-infection81, 82, 88, 89, 92, 93, 103, 104, 107, 110, 117 and seven studies included patients who were non-responders or relapsers following standard interferon therapy.81, 84, 91, 107, 113, 115, 118Table 10 shows the ranges for rates of withdrawals due to adverse events reported in these studies. Rates of withdrawal due to adverse events (and other adverse events) overlapped and ranged widely in trials of dual therapy with pegylated interferon alfa-2b.Table 10Rates of withdrawals due to adverse events reported in uncontrolled studies. This body of evidence does not provide additional evidence about comparative safety or tolerability of dual therapy with pegylated interferon beyond data reported in clinical trials. The type and incidence of adverse events observed were similar to those reported in trials. Most studies followed patients for 24 weeks post-treatment. The longest period of follow-up was 84 weeks. Almost all of the studies were non-comparative, and ranges for rates of adverse events overlapped for dual therapy with the two pegylated interferons.Key Question 3. Does the comparative effectiveness or tolerability and safety of peginterferon alfa-2a plus ribavirin versus peginterferon alfa-2b plus ribavirin vary in patient subgroups defined by demographics (age, racial groups, gender, genotype, markers of disease severity), use of other medications, or presence of co-morbidities (such as HIV infection)?SummaryThere is insufficient evidence to determine if comparative efficacy or safety of dual therapy with pegylated interferon alfa-2a versus dual therapy with pegylated interferon alfa-2b varies in specific patient subgroups. Data from head-to-head trials are limited to one short-term head-to-head trial in patients with genotype 1 infection. Estimates from indirect analysis of SVR for specific HCV genotypes and in HIV co-infected patients are too imprecise to make reliable judgments about comparative efficacy. There are almost no data to determine whether comparative efficacy or safety varies according to race, gender, age, presence of obesity, severity of baseline disease, or other co-morbid conditions.Race, gender, or ageSome studies have found older age40, 44, 48, 62 and black race95, 106, 127 to be associated with poorer response to dual therapy with pegylated interferon. However, we found no studies evaluating whether comparative effectiveness and safety of dual therapy with pegylated interferon alfa-2a versus dual therapy with pegylated interferon alfa-2b varies according to race, gender, or age. In all trials except for one,72 the majority of enrollees were male. Average age in the trials ranged from 34 years35 to 54 years,74 with the exception of a trial of thalassemic patients with a mean age of 20 years.53Race was not reported in the two short-term, head-to-head trials.71, 72 Race was reported in four of 19 other trials comparing dual therapy with pegylated interferon to either dual therapy with non-pegylated interferon or to pegylated interferon monotherapy.44, 48, 57, 73 The proportion of black enrollees ranged from 5% to 33% in these trials. One small subgroup analysis (N=32) of Mexican patients enrolled in a large, international multicenter trial48 reported SVR rates of 50% (7/14) for dual therapy with pegylated interferon alfa-2a versus 33% (4/12) for dual therapy with non-pegylated interferon alfa-2b.38 Other trials have been conducted in Saudi Arabia or Egypt and in Asia.34, 46, 47, 59 Two non-randomized studies reported adverse events rates in black patients compared to white patients.95, 106 However, no study directly compared efficacy or safety of dual therapy with pegylated interferon alfa-2a versus dual therapy with pegylated interferon alfa-2b by ethnic or racial subgroups.HCV genotypeSeveral trials of dual therapy with pegylated interferon have found HCV genotype 1 independently associated with a lower likelihood of SVR.43, 48, 58, 59, 61, 73 One small (N=36), short-term, head-to-head trial directly compared dual therapy with pegylated interferon alfa-2a to dual therapy with pegylated interferon alfa-2b in patients with HCV genotype 1 infection.71 Because of it's small size, short duration of follow-up, and non-standard dosing (4 weeks of monotherapy followed by 4 weeks of dual therapy), it is of very limited value for judging comparative efficacy (see Key Questions 1 and 2). The large (N=2,880) IDEAL study is a head-to-head trial in patients with HCV genotype 1 infection, but results are not yet available.129Twelve trials provide indirect evidence on efficacy of dual therapy with pegylated interferon alfa-2a versus dual therapy with pegylated interferon alfa-2b. Eight trials of dual therapy with pegylated interferon versus dual therapy with non-pegylated interferon restricted enrollment to genotype 1 patients70, 74 or reported subgroup results for patients with genotype 1 infection.44, 45, 48, 59, 63, 73 Four trials reported results for the subgroup of patients with either genotype 1 or 4 infection.43, 45, 58, 61 Six trials reported results for patients infected with HCV genotype 2 or 3.45, 48, 58, 61, 63, 73 Three trials reported SVR in patients with genotype 1 or genotypes 1 or 4 randomized to dual therapy with pegylated interferon versus pegylated interferon monotherapy.42, 48, 56There is insufficient evidence from pooled analyses to conclude that dual therapy with one pegylated interferon is superior to the other for HCV genotypes 1, 2, or 3 infection. Estimates of relative risk for SVR on dual therapy with pegylated interferon alfa-2a versus dual therapy with non-pegylated interferon and for dual therapy with pegylated interferon alfa-2b versus non-pegylated interferon were imprecise (particularly for trials of dual therapy with pegylated interferon alfa-2a), with overlapping confidence intervals (Table 11).Table 11Pooled analyses on sustained virologic response rates for genotypes 1, 2, and 3. We included one systematic review that found dual therapy with pegylated interferon alfa-2a superior to dual therapy with pegylated interferon alfa-2b for achieving SVR in patients with HCV genotype 4.79 HCV genotype 4 is far more common in Egypt, Saudi Arabia, and other North African Countries (up to two-thirds of infected patients) than in North America and Europe (less than 4% of patients in the two largest trials48, 63). The systematic review included subgroup data from the two largest published trials48, 63 and data from four other trials of patients with HCV genotype 4 infection published as conference abstracts (one trial since published as a journal article).34 All of the trials compared dual therapy with pegylated interferon to dual therapy with non-pegylated interferon (three trials of pegylated interferon alfa-2a and three pegylated interferon alfa-2b). Compared to dual therapy with non-pegylated interferon, the systematic review found dual therapy with pegylated interferon alfa-2a significantly superior for achieving an SVR (RR 2.41, 95% CI 1.35 to 4.13), but no significant difference for dual therapy with pegylated interferon alfa-2b (RR 1.17, 95% CI 0.80 to 1.70). However, all of the trials of dual therapy with pegylated interferon alfa-2b used lower, non-weight based doses of ribavirin and two of the three trials did not use FDA-approved body-weight based doses of pegylated interferon. In addition, conclusions about relative efficacy from this data are likely to be misleading, as confidence intervals overlap for the two dual pegylated interferon regimens, and no formal indirect analysis was performed. We re-analyzed the data from the systematic review with additional data from two new trials45, 46 of patients with HCV genotype 4 infection. Our indirect analysis shows no significant differences between pegylated interferon regimens on indirect analysis, with very wide confidence intervals (Table 12).Table 12Direct and indirect analyses on sustained virologic response rates for dual therapy with pegylated interferon. Baseline viral load and histologic findingsSeveral trials of dual therapy with pegylated interferon have found lower viral loads associated with a greater likelihood of achieving an SVR, particularly in patients with genotype 1 infection.44, 48, 50, 63, 73 Analyses of the association between less severe baseline histologic findings and greater response to dual therapy with pegylated interferon are less consistent, with some trials showing no association after controlling for other factors.40, 43, 44, 46We identified no trials evaluating comparative effectiveness or safety of dual therapy with pegylated interferon alfa-2a versus dual therapy with pegylated interferon alfa-2b in patients with higher viral loads, more severe fibrosis or inflammation, or other markers of more severe baseline HCV disease.Obese patientsSubgroup analyses of three trials found dual therapy with pegylated interferon alfa-2a48 and alfa-2b42, 63 less effective at achieving an SVR in patients over 75 to 80 kg, compared to those below 75 to 80 kg. A potential advantage of pegylated interferon alfa-2b is that it is normally dosed according to weight (compared to uniform dosing for pegylated interferon alfa-2a), which could theoretically help insure adequate drug levels in more obese patients. However, no trials have evaluated whether dual therapy with pegylated interferon alfa-2b is superior to dual therapy with pegylated interferon alfa-2a in obese patients, or whether weight-based versus standardized dosing is more effective in such patients.HIV co-infectionHCV infection is present in approximately 30% of HIV-infected persons. We identified no head-to-head trial comparing dual therapy with pegylated interferon alfa-2a to dual therapy with pegylated interferon alfa-2b in HIV co-infected patients. We also found insufficient indirect evidence to determine if dual therapy with interferon alfa-2a differs from dual therapy with interferon alfa-2b for efficacy or safety. Three trials35, 44, 73 compared pegylated interferon alfa-2a versus dual therapy with non-pegylated interferon alfa-2a or alfa-2b, and four trials43, 45, 58, 68 compared pegylated interferon alfa-2b versus dual therapy with non-pegylated interferon alfa-2b in HIV co-infected patients. Pooled rates of sustained virologic response were 3.22 (95% CI, 2.36 to 4.39) and 1.63 (95% CI 1.07 to 2.48), respectively (see Figures 2 and 3). However, the latter analysis included the only trial to report lower rates of SVR on dual therapy with pegylated interferon compared to dual therapy with non-pegylated interferon.68 This was the only non-randomized trial and was rated poor-quality. Excluding this trial, the relative risk for SVR was 1.70 (95% CI 1.25 to 2.32). Rates of SBR were only reported in one trial of HIV co-infected patients.58 Risk of withdrawal due to adverse events were similar in three trials of dual therapy with pegylated interferon alfa-2a versus dual therapy with non-pegylated interferon alfa-2a (RR 0.86, 95% CI 0.59 to 1.25) and three trials of dual therapy with pegylated interferon alfa-2b versus dual therapy with non-pegylated interferon alfa-2b (RR 1.12, 95% CI 0.76 to 1.65). We did not perform indirect analysis because of overlapping confidence intervals and small numbers of trials.Other co-morbid conditionsThere is no evidence to evaluate comparative efficacy or safety of dual therapy with pegylated interferon alfa-2a versus dual therapy with pegylated interferon alfa-2b in patients with severe psychiatric illness or decompensated cirrhosis. Such patients were excluded from the trials and no observational studies were designed to evaluate these patient populations.Some randomized trials and observational studies included patient populations not represented well in clinical trials, such as patients with thalassemia,53 patients on hemodialysis,131 patients with mixed cryoglobulinemia,83, 102 and patients on methadone maintenance.101 However, there was no evidence of clear difference in estimates of efficacy or safety from these studies compared to efficacy or safety of dual therapy with pegylated interferon in general.
Oregon.Bookshelf ID: NBK10667Contents< PrevNext >
ViewsPubReaderPrint ViewCite this PageChou R, Carson S, Chan BKS, et al. Drug Class Review: Pegylated Interferons for Chronic Hepatitis C Infection: Final Report [Internet]. Portland (OR): Oregon Health & Science University; 2007 May. Results.PDF version of this title (813K)In this PageOverviewOverview of methodological quality of included trialsKey Question 1. What is the comparative effectiveness of regimens of peginterferon alfa-2a plus ribavirin versus peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C virus infection?Key Question 1a. How does duration of treatment or dosing protocols (including weight-based or maintenance dosing or dosing of ribovirin) affect estimates of comparative effectiveness?Key Question 2. What is the comparative tolerability and safety of peginterferon alfa-2a plus ribavirin versus peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C virus infection?Adverse events reported in uncontrolled studiesKey Question 3. Does the comparative effectiveness or tolerability and safety of peginterferon alfa-2a plus ribavirin versus peginterferon alfa-2b plus ribavirin vary in patient subgroups defined by demographics (age, racial groups, gender, genotype, markers of disease severity), use of other medications, or presence of co-morbidities (such as HIV infection)?Other titles in this collectionDrug Class ReviewsRecent ActivityClearTurn OffTurn OnResults - Drug Class Review: Pegylated Interferons for Chronic Hepatitis C Infec...Results - Drug Class Review: Pegylated Interferons for Chronic Hepatitis C InfectionYour browsing activity is empty.Activity recording is turned off.Turn recording back onSee more...

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Patent US7032621 - High temperature line expansion installation with release agent - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign in<nobr>Advanced Patent Search</nobr>PatentsA high temperature pre-insulated piping system is shown which can withstand conveyance temperatures in excess of 250� F. The piping system includes a first and second length of insulated and jacketed pipe. Each pipe length includes an inner metal pipe having an interior surface and an exterior surface...http://www.google.com/patents/US7032621?utm_source=gb-gplus-sharePatent US7032621 - High temperature line expansion installation with release agentAdvanced Patent SearchPublication numberUS7032621 B2Publication typeGrantApplication numberUS 10/945,175Publication dateApr 25, 2006Filing dateSep 20, 2004Priority dateSep 20, 2004Fee statusLapsedAlso published asUS20060060256Publication number10945175, 945175, US 7032621 B2, US 7032621B2, US-B2-7032621, US7032621 B2, US7032621B2InventorsThomas Joseph KeyesOriginal AssigneeThermacor Process, LpExport CitationBiBTeX, EndNote, RefManPatent Citations (18), Referenced by (3), Classifications (13), Legal Events (12) External Links: USPTO, USPTO Assignment, EspacenetHigh temperature line expansion installation with release agentUS 7032621 B2Abstract A high temperature pre-insulated piping system is shown which can withstand conveyance temperatures in excess of 250� F. The piping system includes a first and second length of insulated and jacketed pipe. Each pipe length includes an inner metal pipe having an interior surface and an exterior surface and having an envelope of foamed insulation surrounding the inner pipe exterior surface. A special release agent is applied between the metal pipe exterior and the surrounding layer of foamed insulation. The release agent causes intentional disbondment of the foamed insulation layer from the inner metal pipes under certain conditions of environmental stress.
1. An insulated piping system for conveying high temperature fluids, comprising:
a first and second length of insulated and jacketed pipe, each having a joining end to be joined to an end of the other length, each pipe length comprising an inner carrier pipe having an interior surface and an exterior surface, an envelope of foamed insulation surrounding the innerpipe exterior surface, and an outer protective jacket surrounding the envelope of insulation, the joining ends of adjacent pipe lengths being welded together to form fixed joints, whereby the adjacent pipe lengths provide a continuous fluid conduit for conveying high temperature fluids;
wherein a special release agent is applied to at least selected locations on the exterior surface of the inner carrier pipes and wherein the envelope of foamed insulation is then applied over the release agent, the release agent being selected to intentionally fail at conditions of predetermined environmental stress, so that the disbondment of the surrounding envelope of insulation from the inner carrier pipes occurs in a predictable, uniform fashion rather than in a haphazard fashion.
2. The insulated piping system of claim 1, further comprising:
a flexible tubular bellows surrounding the joining ends of the inner pipes, the bellows being capable of being axially expanded and contracted and of being configured in a straight or curved axial configuration, the tubular bellows having opposing outer extents which are joined to the respective protective jackets of the respective pipe lengths being coupled thereby.
3. The insulated piping system of claim 1, wherein the foam insulation is selected from the group consisting of polyurethane foams and high temperature polyisocyanurate foams.
4. The insulated piping system of claim 1, wherein the protective jackets are formed from a synthetic polyolefin.
5. The insulated piping system of claim 1, wherein the inner carrier pipe is a steel pipe.
6. The insulated piping system of claim 1, wherein the release agent initially bonds to both the exterior surface of the inner carrier pipes and to the surrounding foamed insulation at an interface layer.
7. The insulated piping system of claim 1, wherein the release agent is a material which does not bond to the exterior surface of the inner carrier pipes.
8. The insulated piping system of claim 1, wherein the lengths of insulated piping are part of a pipeline conveying steam, hot water or other hot fluids at a temperature above about 250� F.
9. The insulated piping system of claim 1, wherein the release agent is selected from the group consisting of polyolefin sprays and wraps.
10. The insulated piping system of claim 1, wherein the release agent is selected from the group consisting of polytetrafluoroethylene and other non-stick materials.
11. The insulated piping system of claim 1, wherein the release agent forms a layer of a predetermined thickness on the exterior surface of the inner carrier pipes, the thickness being in the range from about 2�50 mils.
12. A method of controlling the disbondment of a surrounding foam insulating layer in a pre-insulated piping system, the method comprising the steps of:
providing a first and second length of insulated and jacketed pipe, each having a joining end to be joined to an end of the other length, each pipe length comprising an inner metal pipe having an interior surface and an exterior surface;
applying a layer of a special release agent onto at least selected regions of the exterior surface of the inner metal pipes;
applying an envelope of foamed insulation which surrounds the inner pipes exterior surface and envelopes the inner pipes;
applying an outer protective jacket which surrounds the envelope of insulation, the joining ends of adjacent pipe lengths being welded together to form fixed joints, whereby the adjacent pipe lengths provide a continuous fluid conduit for conveying high temperature fluids;
wherein the special release agent is selected to intentionally fail at conditions of predetermined environmental stress, so that the disbondment of the surrounding envelope of insulation from the inner metal pipes occurs in a predictable, uniform fashion rather than in a haphazard fashion.
installing an expansion compensating mechanism adjacent the region of the inner pipes where the release agent was applied to accommodate movement of the envelope of formed insulation and of the inner metal pipes.
installing a flexible tubular bellows surrounding the joining ends of the inner pipes, the bellows being capable of being axially expanded and contracted and of being configured in a straight or curved axial configuration, the tubular bellows having opposing outer extents which are joined to the respective protective jackets of the respective pipe lengths being coupled thereby.
15. The method of claim 12, wherein the foam insulation which is used to surround the inner pipes is a high temperature polyisocyanurate foam.
16. The method of claim 12, wherein the protective jackets are formed of HDPE.
17. The method of claim 11, wherein the lengths of insulated piping are part of a pipeline conveying steam at a temperature above about 250� F.
The present invention relates to pre-insulated piping systems, and more specifically to a method for anticipating and selectively controlling the disbondment of the foam from the carrier pipe which may occur as these systems thermally expand in the presence of high temperature fluids being conveyed.
There are many instances in which insulated pipelines are needed. For example, distributed HVAC (heating, ventilation and air conditioning) applications utilize chilled water for cooling and steam for heating. The chiller and boiler are typically contained in a central location and the chilled water and steam are distributed to other locations. For example, on a school campus, the chiller and boiler may be located in a power plant building. The chilled water and steam are distributed to classrooms in separate buildings.
A set of insulated pipelines is used to convey the chilled water from the chiller to other locations and back to the chiller. Another set of insulated pipelines is used to carry the steam from the boiler to the other locations and back to the boiler. The insulated pipelines are usually located underground.
Insulated pipe is conventional and commercially available. There are predominately two types of piping systems in use: Class-A drainable dryable testable (DDT); and polyurethane or polyisocyanurate �bonded� foam systems. Both of these systems use an inner carrier pipe to convey fluid. Although steel is commonly used for the inner pipe which carries the media to be piped, copper or aluminum or other metals as well as fiberglass, PVC, and similar materials may be utilized, as well. The present application is directed toward the �bonded� foam type system. These systems utilize a steel pipe to convey fluid. Around the outside of the steel pipe is a layer of insulating foam such as, for example, polyisocyanurate foam. Around the outside of the foam is a jacket of hard thermoplastic (such as high density polyethylene, HDPE). The foam has set up or cured within the outer jacket so as to bond to the jacket and to the inner pipe. The plastic jacket protects the foam from mechanical damage and also provides a water tight seal to prevent corrosion of the steel pipe. In the bonded type system, the foam and outer jacket do not move relative to the inner pipe. In the Class-A type system, on the other hand, the insulated inner pipe is designed to move independently of the associated outer jacket. In fact, there is an air gap between the inner pipe and outer carrier pipe in the class-A type system.
The most important engineering criteria for the traditional �bonded� foam type system is that it must be treated as a monolithic system. In other words, the foam is bonded to both the carrier pipe and the outer jacket. Therefore, the bonded system has traditionally been designed to move as a unit underground. Higher temperatures can act adversely upon the bonded foam system, however. The hot fluid in the steel carrier pipe causes the carrier pipe to thermally expand. At temperatures of 400� F. this expansion is on the order of 2.8 inches per 100 feet of pipe. This expansion is not a problem as long as the system remains bonded and the carrier pipe, foam and jacket move together as one unit underground. This movement is controlled by the expansion force of the steel carrier pipe, but it is the bond strength of the foam to the pipe and jacket that is important in keeping the system moving together. This monolithic movement of the system occurs along each incremental length of a particular run, and as long as total movement is not greater than 4 to 6 inches and the system remains bonded, no undue stress is subjected at any one point of the jacket. If the system however were to disbond, the surrounding soil would fix the jacket in place and the carrier pipe would still thermally expand thereby pushing thorough and destroying the jacket at the first change of direction.
Generally speaking, the proper choice of insulating materials can counteract many of the thermal expansion effects discussed above. It has been well established by industry case history that the polyurethane foam bond for systems running at 250� to 300� is strong enough to keep the entire system acting as a bonded system. However, for systems running above these temperatures a higher temperature rated foam, such as polyisocyanurate foam, is required. However, even in systems utilizing �high temperature� polyiscyanurate foam, the higher heat can in some circumstances, begin to fry the foam at the foam/carrier pipe interface, thereby bringing into question the strength of the foam bond to the steel carrier pipe.
Despite the advances which have been made in addressing the above problems, a need exists for improvements in pre-insulated piping systems which will either ensure that the insulating foam remains bonded to the carrier pipe, or which will ensure that the foam bond fails in a predictable manner and at preselected locations.
A need exists for an alternative fo the traditional �bonded� foam system which can be utilized at temperatures exceeding 250� F. to 350� F. without risk of having the carrier pipe rupture the outer jacket at changes of direction.
A need continues to exist for a pre-insulated piping system of the above type which effectively either prevents or accommodates foam disbondment, even at temperatures above 250 to 300� F.
A need also exists for a complimentary mechanical expansion component for such systems which compliments the bonding system and which is activated in the case of movement of the inner steel carrier pipe relative to the foam insulation to prevent the carrier pipe foam pushing through the outer jacket or causing other structural damage to the system.
SUMMARY OF THE INVENTION The present invention employs a different approach to the problem of disbondment in foam pre-insulated piping systems, which approach is, in a sense, a hybrid of the prior art approaches. The system under consideration is essentially an unbonded, high temperature isocyanurate system which, like the prior art Class-A systems is designed to allow the inner carrier pipe to move independently of the outer layers of insulation. However, unlike certain of the unbonded, prior art systems which allowed the intrusion of water and other contaminants, the present system acts more in the nature of the �bonded� foam systems as far as the overall integrity of the system since there is no air gap between the inner pipe and outer carrier pipe and since closed cell foams are used for the surrounding insulating layer.
The present invention has as its general purpose to provide a method for anticipating and selectively controlling the disbondment of the foam from the carrier pipe in a foam bonded pre-insulated piping system which may occur as these systems thermally expand in the presence of high temperature fluids being conveyed and which satisfies the previously described deficiencies.
This object is accomplished by providing an underground piping system capable of servicing temperatures in excess of 250� F. in which a metal carrier pipe is insulated by a high temperature foam. In some circumstances, the unit of piping will remain bonded so that it will move as a single monolithic unit underground. However, the unit of piping is also provided with a release agent as a part of the insulation profile which will ensure that the foam bond fails in a predictable manner and at preselected locations under conditions in which the foam bond would normally fail in an unpredictable manner without the presence of the release agent.
In one embodiment, a first and second length of insulated and jacketed pipe are provided, each having a joining end to be joined to an end of the other length. Each of the pipe lengths comprises an inner metal pipe having an interior surface and an exterior surface. A special release agent is first applied to the exterior surface of the inner metal pipe, as by spraying or wrapping the pipe with a thin layer of the release agent. An envelope of foamed insulation is then applied so that it surrounds the inner pipe exterior surface. An outer protective HDPE jacket surrounds the envelope of insulation.
In one embodiment of the invention, the layer of release agent bonds to both the exterior of the inner pipe and to the surrounding foam insulation. In another embodiment of the invention, the release agent forms a very thin layer or coating on the pipe exterior so that, even without bonding, the envelope of insulation is initially restrained, but later fails in a controlled manner under predetermined conditions of environmental stress. The release agent can comprise, for example, a very thin layer of polyethylene which becomes viscous or liquid at higher temperatures. The joining ends of adjacent pipe lengths are afixed, as by being welded together, to form fixed joints, whereby the adjacent pipe lengths provide a continuous fluid conduit for conveying high temperature fluids.
A mechanical expansion component may also be utilized as a part of the high temperature line installation. In some circumstances, the expansion component is simply an elbow or loop provided in the line installation. In another embodiment of the invention, a tubular bellows surrounds the joining ends of the inner pipes and the layer of previously applied high temperature insulation. The bellows is capable of being axially expanded and contracted and of being configured in a straight or curved axial configuration. The tubular bellows has opposing outer extents which are joined to the foamed insulation surrounding the respective pipe lengths being coupled. The release agent is selectively applied to the metal pipe exterior so that any disbondment which occurs will occur at a predetermined location which can be accommodated by the presence of the bellows or expansion joint.
Any of the bonded foam type pre-insulated piping systems may benefit from the techniques of the present invention. However, those systems in which fluid temperatures in excess of 250� F. are likely to be encountered are perhaps best suited for the practice of the present invention. It is these systems which generally require higher temperature foams and which also bring into question the strength of the foam bond.
BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a simplified representation of a typical distributed HVAC system utilizing chilled water for cooling and steam for heating.
FIG. 2 is a schematic representation of an expansion loop in a pre-insulated pipeline prior to thermal expansion.
FIG. 3 is a schematic view of the pipeline of FIG. 2 under the influence of thermal expansion forces.
FIG. 4 is an isolated view of the bellows used in forming the flexible coupling of the invention;
FIG. 5 is a side, cross-sectional view of the bellows taken along line V�V in FIG. 4;
FIG. 6 is a simplified view of the flexible coupling of the invention showing its relative movement during expansion and contraction of the pipeline;
FIG. 7 is a side partial cross-sectional view of the flexible coupling used to form the expansion installation of the invention;
FIG. 8 is a close-up view of a portion of the flexible coupling of FIG. 7;
FIGS. 9A and 9B are simplified, side views of the first step of the method of the invention in which a special release agent is applied to the exterior surface of the inner metal pipe;
FIG. 10 is a simplified representation of the next step in the method of the invention in which a thermoplastic jacket is positioned about the inner metal pipe and a foam material is placed between the jacket and the exterior surface of the inner pipe;
FIG. 11 is a view similar to FIG. 10 but showing the cured foam which normally bonds to both the inner carrier pipe and to the surrounding thermoplastic jacket; and
FIG. 12 is an end view, partly in section of the completed pre-insulated pipe of the invention and illustrating in exaggerated fashion the layer of release agent which separates the metal pipe exterior surface from the layer of surrounding cured foam.
DETAILED DESCRIPTION OF THE INVENTION Turning first to FIGS. 1�3, there is illustrated a typical environment in which the pre-insulated piping systems of the invention might be employed. FIG. 1 shows a school campus having a number of isolated buildings 3, 5 connected by an underground insulated pipeline carrying steam which at points includes right angle loops or elbows 9.
FIGS. 2 and 3 are schematic views of the standard piping installation of the type under consideration designated generally as 11. The installation 11 includes a number of coaxially oriented lengths of pipe, such as length 13 (shown broken away in FIG. 2). The installation may also include a number of angled fittings such as the right angle elbows (generally shown as 15) in FIG. 2. Each length of pipe includes an inner pipe 17, typically formed of steel, an envelope of foamed insulation 19 surrounding the inner pipe and outer protective jacket 21 surrounding the envelope of insulation. The joining ends (shown generally as 135, 137 in FIG. 7) of adjacent pipe lengths are afixed, as by being welded together, to form fixed joints, whereby the adjacent pipe lengths provide a continuous fluid conduit for conveying high temperature fluids. The jacket 21 (FIG. 1) is typically formed of high density polyethylene (HDPE) or a similar polyolefin type material. The following references, among others, teach the manufacture of such prior art systems: U.S. Pat. No. 3,793,411; U.S. Pat. No. 4,084,842; and U.S. Pat. No. 4,221,405, all to Stonitsch et al.
The piping systems of the type illustrated in FIGS. 2 and 3 are sometimes utilized to convey fluids at high temperature and/or pressures. For example, a typical steam line might be conveying fluid at, for example, 400� F. The temperature differentials which exists between the piping system materials and the fluid being conveyed can cause a force (�F� in FIG. 2) to be applied along the coaxially aligned pipes lengths. If the carrier is free to move independently from the foam and jacket (disbondment has occurred) then the surrounding soil will fix the jacket in place and the carrier pipe will burst through the foam and jacket in areas shown generally as 15 and 13 in FIG. 2.
In the piping system illustrated in FIG. 3, the system is displacing as a unit and moves into both a cushioned bolster padding 26 and the surrounding soil 28. This movement does not damage the jacketing or the foam of the system because they are both incrementally being pulled along throughout the entire length of the straight run. Because of this monolithic movement no one individual section of the jacket is over stressed and thereby ruptured, and no one individual section of the foam is required to support the entire force of the thermal expansion of the pipe. The bond distributes these forces along each incremental length of the entire run. It will be understood, however, that should the forces become great enough, disbondment of the foam from the carrier pipe can occur. In such case, the foam and outer jacket can be ruptured, as illustrated generally at 25 in FIG. 3. Failure of the surrounding insulated layers allows water or other contaminants to contact the steel pipe, leading to increased corrosion and joint failure in some cases.
The present invention is directed toward an expansion installation for high temperature insulated piping systems of the type illustrated generally in FIGS. 1�3. The present invention is intended to provide a solution for possible disbondment problems for foam bonded piping systems that are operating at temperatures in the range of 250� F. and above 250� F. At temperatures that begin to exceed 250� F., foams have been developed that are stable structurally to handle these higher temperature, but the bond strength of the foams at these temperatures may come into question. The invention is intended to prevent the potential problems that might occur if the foam bond strength is not sufficient to cause the system to expand as one monolithic item.
The reference in this discussion to pipe �lengths� is intended to refer to standard available factory pre-insulated piping of the type previously described having an inner metal pipe surrounded by an envelope of foamed insulation, which in turn, is contained within a polyolefin jacket. As referred to briefly above, typical commercial practice involves the use of steel, copper, aluminum or alloy conveying pipes, open or closed cell polyurethane, polyisocyanurate, polystyrene or the like, foamed rigid insulation and polypropylene, polybutylene, polyethylene, polyvinylchloride and similar protective jackets.
The term �high temperature�, as used in this discussion, will be any temperature exceeding 250� F., which is the present temperature limitation at which polyurethane foam is used in bonded foam systems. Temperatures above 250� F. require the use of higher temperature foams, such as polyisocyanurate foam, whose bond strength may come into question.
The present invention is an improvement to presently available pre-insulated piping of the type which is commercially available and familiar to those in the relevant industries. Prior art pipe lengths of this general type are commercially available as standard factory type product. For example, such product is available from Thermacor Process, LP of Fort Worth, Tex., assignee of the present invention. One typical example is sold commercially as the HT-406 High Temp Steel Piping System. The published specifications for systems are as follows:
Carrier Pipe-
diameter less than about 2″
A53 ERW Grade B, Std. Wt.
diameter greater than about 2″
A106 SML, Std. Wt. Black Steel
HDPE Jacket-
Compatible with ASTM D3350
0.941 min.
3100 psi min.
Elongation Ultimate (ASTM D638)
400% min.
2700 psi min.
Impact Strength (ASTM D256)
2.0 ft. lb/in. North Min.
Rockwell Hardness (ASTM D785)
D60 (Shore) min.
Polyisocyanurate Insulation-
>2.4 lbs/ft3 �K� Factor
≦0.14 @ 70� F.,
≦0.24 @ 406� F.
>30 psi
≧2.5″ @ 366� F.,
≧3.0″ @ 406� F.
The present invention preferably incorporates an expansion component to accommodate movement of the inner pipe relative to the outer jacket and insulation. The expansion component may be as simple as a loop or elbow in the piping, as previously described. In one aspect, the present invention incorporates a mechanical expansion joint, or bellows, to accommodate line expansion forces. Such a preferred expansion joint is described in our co-pending patent application, entitled �HIGH
TEMPERATURE LINE EXPANSION INSTALLATION WITH BELLOWS�, serial no. 09/748,058, filed concurrently herewith. The present invention also concerns the additional discovery that many of the problems associated with disbondment of the prior art systems, such as those described above, can be overcome by applying a special release agent to the exterior surface of the inner metal pipes prior to applying the insulating foam layer. An envelope of foamed insulation can then be applied over the thermally protective coating. The release agent may bond to both the exterior surface of the inner metal pipe and to the surrounding foamed insulation at an interface layer. Alternatively, the release agent may be sufficiently thin to initially restrain the foam outer layer, but to then allow relative movement in a controlled fashion in the presence of predetermined environmental stresses, such as increased temperature and consequent pipe expansion. In this situation, the system is, in effect, an unbonded high temperature isocyanurate system.
In one form, the special release agent is a polyethylene wrap which is on the order of 5 mil thick. A corona treated sheet of polyethylene can be applied to the exterior of the steel pipe using conventional processing equipment, as will be explained in the discussion which follows. The polyethylene has an upper temperature limit of approximately 255� F. before it begins to soften and become viscous. The polyethylene wrap will thus act as a release agent which designs a controlled failure aspect into the product once a given temperature is reached due to the hot fluid being conveyed within the inner carrier pipe. The advantage of having a controlled failure is that the exact point of failure can be predicted and further accommodated, as with a mechanical expansion joint, or other technique. Also, the failure occurs uniformly, with all of the insulation coming loose at one time in a predictable manner.
Other release agents can be utilized, as well. For example, other thermoplastic polyolefins such as polypropylene, or traditional non-stick coatings such as polytetrafluoroethylene (PTFE), also known as TEFLON� may be sprayed or wrapped about the exterior surface of the steel pipe. The preferred wraps or coatings are much thinner than the prior art composite systems, such as those incorporating a layer of PERLITE�, for added insulatory properties. The release agent forms a layer of a predetermined thickness on the exterior surface of the inner metal pipes, the thickness being in the range from about 2�50 mils. The preferred thin layer of release agent is less than about 40�50 mils thick preferably less than about 10 mils thick and, most preferably in the case of a polyethylene wrap, is on the order of about 5 mils thick.
Turning now to FIGS. 9�12, the various steps in the method of the invention are illustrated. An inner metal or carrier pipe 39 has the special release agent of the invention applied thereto. In FIG. 9A, the release agent takes the form of a 5 mil wrap of polyethylene which is dispensed from the dispenser head 41. In FIG. 9B, the release agent takes the form of a TEFLON� spray in which particles of adherent TEFLON� are dispensed by the directional spray nozzle 42. In the case of the polyethylene wrap, the layer of release agent is initially bonded to both the inner metal pipe and the outer layer of foam insulating material. In the case of the TEFLON� spray, the layer of release agent is not typically bonded to the metal of the pipe. In FIG. 10, the coated pipe 39 is surrounded by the outer thermoplastic jacket 43 which is positioned by means of standoffs 45, 47. A foam insulating material from a suitable supply source 49 is then pumped into the annular space 51 between the pipe exterior and the interior of the thermoplastic jacket and allowed to set (illustrated as 53 in FIG. 11). In the particular embodiment of the invention illustrated in FIG. 11, the surrounding foam insulation layer 53 is typically polyisocyanurate foam insulation for systems above 250� F. FIG. 12 shows the layer of release agent, in exaggerated fashion as 44. The surrounding jacket 43 is a polyolefin, preferably HDPE.
From the above discussion, it will be appreciated that the pre-insulated piping system of the invention shares certain of the desirable features of both the Class-A drainable dryable testable (DDT) systems and the polyurethane or polyisocyanurate �bonded� foam systems. Like the prior Class-A system, the present system intentionally anticipates and allows for movement of the inner carrier pipe relative to the outer stationary jacket. The action of the improved system in allowing the inner pipe to move independently alleviates stress in the outer polyethylene jacket. At the same time, the present system resembles the prior bonded systems in providing a sealed environment for the carrier pipe which resists the intrusion of water or other contaminants which could cause rust or corrosion.
The designed failure mode which results from employing a release agent in the manner previously described allows the controlled disbondment which occurs to be accommodated by a mechanical mechanism, such as a mechanical expansion joint or other failure compensating mechanism. FIGS. 4�8 illustrate one mechanical expansion system which can be utilized with the restraint system of the invention.
The expansion joint or coupling is designated generally as 127 in FIG. 7. The coupling 127 would typically be used in a coaxially aligned piping system where the lengths encounter an angular fitting such as the elbow 15 (FIG. 2). However, for purposes of the present invention, the coupling 127 may also be employed in a straight run of pipe, where the release agent has been installed to provide controlled failure adjacent that point. The coupling 127 is particularly advantageous in countering the harmful effects of coaxial stresses which are often encountered in a �high temperature� insulated piping system, however. The term �high temperature� is intended to encompass any temperature above ambient which would tend to cause the type of damage to the surrounding insulating layers of the piping system discussed with respect to FIGS. 1�3 above. Typically, such temperatures will be above about 200� F., often above 250� F., and in some cases temperatures of 400� and higher will be encountered.
The flexible coupling 127 of the invention includes a first length 131 and a second length 133 (both shown broken away in FIG. 7) of insulated and jacketed pipe. Each of the lengths 131, 133 has a joining end 135 to be joined to a similar end 137 of the other length. Each pipe length comprises an inner pipe 139, 141, an envelope of foamed insulation 143, 145 surrounding the inner pipe and an outer protective jacket 147, 149 surrounding the envelope of insulation. The first and second pipe lengths 131, 133 can be standard factory type product of the kind described above and available from Thermacor Process, LP of Fort Worth, Tex., except that at least selected lengths of the inner metal pipes are coated with the special release agent, as previously described.
As shown in FIG. 7, each innerpipe 139, 141 projects beyond the end of the envelope of insulation and beyond an end of the jacket to form initially exposed joining ends 135, 137. The joining ends 135, 137 of steel pipe will typically be welded together (illustrated by the vertical line in FIG. 7) in order to form a continuous fluid conduit for conveying high temperature fluids.
In the particular embodiment of the invention illustrated in FIG. 7, the surrounding foam insulation layers 143, 145 are typically polyurethane closed cell foam insulation for systems of up to about 250� F. and polyisocyanurate foam insulation for systems above 250� F. The surrounding jacket 147, 149 is a polyolefin, preferably HDPE.
As shown in FIGS. 7 and 8, a layer of high temperature insulation 157 preferably surrounds the joining ends 135, 137 of the inner pipes 139, 141 and extends between the outer points 140, 142, respectively. The layer 157 can comprise a polyurethane foam for systems under 250� F. or a polyisocyanate foam for systems above 250� F. In some cases, it is possible to place a hollow jacket about the pipe joining ends 135, 137 with a two part commercially available mix being added through a hole in the jacket and allowed to cure. However, in the preferred method of forming the piping installation of the invention, the insulating layer for the joining ends of the pipe is preformed at the factory and provided as two side half cuts which are placed about the pipe joining ends to form a concentric cylinder. Each half cut is formed from a �crushable� foam so that the foam will be crushed or broken up upon relative movement of the inner pipes 139, 141. Note also that the crushable foam layer 157 is not joined to the exposed joining ends of the inner pipes or to the protective jackets, allowing its movement relative to these other components of the piping installation.
A tubular bellows 159 (FIGS. 4 and 5) which can also be formed of HDPE surrounds the joining ends of the inner pipes. The bellows is capable of axially expanded and contracted and of being configured in a straight or axial configuration. The tubular bellows has opposing outer extents 161, 163 (FIGS. 7 and 8) which are joined to the prospective protective jackets of the respective pipe lengths being coupled. For example, the outer extent 163 is joined to the jacket 147 of the pipe end 133 in FIG. 8. This can be accomplished in a number of ways. For example, a commercially available POWERCORE� welding wire (illustrated in simplified fashion as 151, 153 in FIG. 8) can be used to electrofuse and join the opposite extents of the tubular bellows 159 and the outer exposed surface of the HDPE jacket. The outer extent 163 of the bellows surrounds the jacket 147 and resistive wires 151, 153. Upon applying an electric current to the wires, a weld between the bellows and jacket is achieved. The entire bellows assembly can be covered with a protective shield, if desired. The shield (165 in FIG. 7) could be formed of lightweight metal or from a suitable thermoplastic. In the preferred embodiment illustrated in FIGS. 7 and 8, a polyethylene shield 165 has flanges 166 which are received upon the outer extents of the bellows. If desired, a suitable resistive wire arrangement can be used to simultaneously electrofuse the bellows and shield, since both the bellows and shield can be formed of a HDPE type material.
FIG. 6 illustrates the insulated piping installation of the invention with the flexible coupling 127 in place. In FIG. 6, the protective sleeve or shield 165 is not shown in order to better illustrate the action of the bellows 159. The force F, tends to cause the inner steel pipe 117 to assume the path illustrated by the dotted lines in FIG. 6. Because the bellows 159 can expand and contract, however, outer jacket remains intact and the integrity of the foam insulations (143 in FIGS. 6 and 7) is not disrupted. Because the insulating layer 143 remains intact, water or other contaminants are prevented from reaching the inner steel pipe 117, thereby extending the useful life of the pipeline.
An invention has been provided with several advantages. The pre-insulated piping systems of the invention can normally be designed so that disbondment of the foam does not occur, as through the selection of appropriate materials for the inner insulating foam layer and the outer jacket. In those situations in which excessive environmental stress is encountered, such as elevated temperatures, the special release agent causes a designed failure in the system at preselected locations along the pipeline. A mechanical expansion joint, or other compensating mechanism, can be placed at an appropriate location to alleviate problems previously encountered with high temperature piping systems where elbows, other angled fittings, and other pipe locations were subjected to damaging stresses. The system incorporates several existing, commercially available materials or components, thereby simplifying manufacture and assembly. The release agent can be easily applied as one step in the already existing manufacturing process and adds little expense to the overall operation. The particular bellows and additional flexible coupling components of the system compensate for relative movement of the inner steel pipe. The coupling is simple in design and economical to implement in a variety of industrial applications.
While the invention has been shown in one of its forms, it is not thus limited but is susceptible to various changes and modifications without departing from the spirit thereof.
Patent CitationsCited PatentFiling datePublication dateApplicantTitleUS2903018 *Dec 22, 1954Sep 8, 1959Zonolite CompanyParting agent for conduitsUS3359016Oct 11, 1965Dec 19, 1967Ltv Aerospace CorpPressure balanced flexible jointUS3642034 *Oct 7, 1970Feb 15, 1972Owens Corning Fiberglass CorpTubular fibrous bodies and apparatus and method for their productionUS3766357 *Jul 26, 1971Oct 16, 1973Haynes Electric Heating CoHigh power factor pipe heaterUS3793411 *Apr 20, 1971Feb 19, 1974Rovanco IncMethod for making insulated pipeUS3837685Jan 2, 1973Sep 24, 1974J MillerPipe expansion and repair fittingUS3865145 *May 10, 1973Feb 11, 1975Foundation Cryogenic Joint VenPipeline systemUS3865662 *Apr 6, 1973Feb 11, 1975Allied ChemMethod for sealing shell-like thermoplastic objectsUS3885595 *Jan 28, 1974May 27, 1975Kaiser Aerospace & ElectronicsConduit for cryogenic fluid transportationUS4084842 *Jul 12, 1976Apr 18, 1978Lawrence StonitschConduit system with expansion couplingUS4221405 *Mar 8, 1978Sep 9, 1980Stonitsch Lawrence JConduit system with expansion coupling and combined spacer and sealing sleeveUS4239267Sep 10, 1979Dec 16, 1980The Dow Chemical CompanyInternal-bellows, pressure-balanced, angled-flowpath expansion jointUS4350372Jul 21, 1980Sep 21, 1982Logsdon Duane DExpansion coupling for large diameter plastic pipesUS4484386Nov 1, 1982Nov 27, 1984Rovanco Corp.Method of field insulating pipe jointsUS5058934Jan 28, 1991Oct 22, 1991Brannon Duane AFlexible and extendible pipe sectionUS5072591 *Oct 17, 1989Dec 17, 1991Hypres IncorporatedFor transferring cooling liquidUS6527015 *Dec 7, 2001Mar 4, 2003F. Glenn LivelyInsulated pipeUS6910506 *Nov 12, 2002Jun 28, 2005Benteler Automobiltechnik GmbhExhaust pipe, and method of making an exhaust pipe* Cited by examinerReferenced byCiting PatentFiling datePublication dateApplicantTitleUS7418979 *Jan 19, 2007Sep 2, 2008Thermacor Process, L.P.Method and apparatus for preventing foam disbondmentUS8371338 *Sep 18, 2009Feb 12, 2013Armacell Enterprise GmbhFoam insulation structure and method for insulating annular ductsUS20100071289 *Sep 18, 2009Mar 25, 2010Armacell Enterprise GmbhFoam insulation structure and method for insulating annular ducts* Cited by examinerClassifications U.S. Classification138/120, 138/155, 285/45, 285/299, 285/228, 138/149, 138/145, 138/118International ClassificationF16L9/22Cooperative ClassificationF16L59/15, F16L59/143European ClassificationF16L59/15, F16L59/14FLegal EventsDateCodeEventDescriptionJun 17, 2014FPExpired due to failure to pay maintenance feeEffective date: 20140425Apr 25, 2014LAPSLapse for failure to pay maintenance feesDec 6, 2013REMIMaintenance fee reminder mailedOct 14, 2013ASAssignmentOwner name: THERMACOR PROCESS, INC., TEXASFree format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:THERMACOR PROCESS, L. P.;REEL/FRAME:031399/0359Effective date: 20131010Jul 25, 2011PRDPPatent reinstated due to the acceptance of a late maintenance feeEffective date: 20110726Apr 6, 2011SULPSurcharge for late paymentApr 6, 2011FPAYFee paymentYear of fee payment: 4Jun 15, 2010FPExpired due to failure to pay maintenance feeEffective date: 20100425Apr 25, 2010LAPSLapse for failure to pay maintenance feesApr 25, 2010REINReinstatement after maintenance fee payment confirmedNov 30, 2009REMIMaintenance fee reminder mailedSep 20, 2004ASAssignmentOwner name: THERMACOR PROCESS, LP, TEXASFree format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:KEYES, THOMAS JOSEPH;REEL/FRAME:015817/0867Effective date: 20040917RotateOriginal ImageGoogle Home - Sitemap - USPTO Bulk Downloads - Privacy Policy - Terms of Service - About Google Patents - Send FeedbackData provided by IFI CLAIMS Patent Services©2012 Google

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