Efficacy of a new prostaglandin E1 regimen in outpatients with severe intermittent claudication: results of a multicenter placebo-controlled double-blind trial. Intermittent intraarterial infusion therapy with PGE1 in patients with severe claudication--results of a randomized prospective double blind study. A randomized trial of iloprost in patients with intermittent claudication. Clinical and haemorheological efficacy of i.a. PGE1 infusions in intermittent claudication. Impact of a 4-week treatment with prostaglandin E1 on health-related quality of life of patients with intermittent claudication. Pharmacologic treatment of intermittent claudication. Pentoxifylline efficacy in the treatment of intermittent claudication: multicenter controlled double-blind trial with objective assessment of chronic occlusive arterial disease patients. The effects of prostaglandin E-1 in patients with intermittent claudication. Treatment efficacy of intermittent claudication by surgical intervention, supervised physical exercise training compared to no treatment in unselected randomised patients I: one year results of functional and physiological improvements. A long-term study of policosanol in the treatment of intermittent claudication. Randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of AS-013, a prostaglandin E1 prodrug, in patients with intermittent claudication. EDTA treatment of intermittent claudication--a double-blind, placebo-controlled study. Effect of oral prostaglandin E2 on uterine contractility and outcome of treatment in women receiving RU 486 (mifepristone) for termination of early pregnancy. Effect of prostaglandin E1 on idiopathic sudden sensorineural hearing loss: a double-blinded clinical study. Flunisolide nasal spray for perennial rhinitis in children. Randomized double-blind, multicenter study of prostaglandin E1 in patients with the adult respiratory distress syndrome. Prostaglandin E1 Study Group.
For the first time efficacy and safety of a new prostaglandin E1 (PGE1) regimen in the treatment of intermittent claudication were evaluated in a randomized, double-blind, placebo-controlled multicenter clinical trial. The study involved 213 outpatients with a maximum walking distance of 50 to 200 m measured on the treadmill (3 km/hr, 12% grade). After a 2-week run-in phase they received a 2-hour intravenous infusion of 60 micrograms PGE1 or placebo 5 days a week for 4 weeks. It was followed by a 4-week interval treatment with the same medication administered only twice a week. Patients were monitored for 3 months when they received no study medication. In the PGE1 group the intention-to-treat analysis (n = 208) revealed an increase in walking distance after 4 weeks of 75% (placebo, 43%). At the end of the interval treatment the walking distance had improved to 101% (placebo, 60%). The results remained virtually constant during follow-up (PGE1, 104%, placebo, 63%). Between-group comparisons showed significant differences in favor of PGE1 for all three time points of measurement (p < 0.05, p < 0.01, and p < 0.05). PGE1 was well tolerated; the rate of adverse reactions related to the treatment was 12.8% (placebo, 7.7%). In summary, these results show that the new PGE1 regimen is effective and safe in the treatment of outpatients with intermittent claudication. In a randomized prospective double blind study, intraarterial infusion therapy with prostaglandin E1 (PGE) was tested against infusion therapy with energy rich phosphates (ERP) in 40 patients with severe claudication. During the treatment period of three weeks, a significant increase of the painfree (PWD) and maximal walking distance (MWD) was observed. The improvement of PWD was of clinical relevance (PGE: 60----195 m; ERP: 69----170 m; p less than 0.001) and persisted during a 36 week post treatment observation period. The differences between the two drugs were not significant but showed a tendency in favour of the PGE therapy. Prostanoids, which promote vasodilation and reduce platelet aggregation, have been proposed as candidate therapies for intermittent claudication due to peripheral arterial disease (PAD). However, studies of these medications have yielded inconsistent results. This study tested the hypothesis that iloprost, an oral prostacyclin analogue, would improve walking distance and quality of life in patients with intermittent claudication. The study was a multi-center, randomized, double-blind, placebo-controlled trial comparing three doses of oral iloprost (50 microg, 100 microg, or 150 microg twice daily), pentoxifylline, or placebo in 430 patients with intermittent claudication. The primary outcome measure was improvement in absolute claudication distance (ACD) after 6 months. Secondary outcomes included initial claudication distance and quality of life assessment. Placebo increased ACD by 3.3%, and iloprost increased peak ACD by 7.7%, 8.8% and 11.2% at the 50 microg, 100 microg, and 150 microg twice-daily doses, respectively (all insignificant relative to placebo). Pentoxifylline increased ACD by 13.9% relative to placebo (p = 0.039). Neither iloprost nor pentoxifylline enhanced quality of life. These results indicate that oral iloprost is not effective in improving exercise performance or quality of life in patients with PAD who have intermittent claudication. nan Intermittent claudication impairs functional status and quality of life in many patients by limiting walking capacity. The aim of this study was to evaluate the effects of a 4-week treatment with prostaglandin E1 (PGE1), a drug inducing vasodilation and inhibiting platelet aggregation, on improving functional status and health-related quality of life in patients with disabling intermittent claudication. Forty-two untrained outpatients (37 men and five women, mean age 64 +/- 8 years) with intermittent claudication,and maximum walking distance (MWD) of at least 50 and no more than 200 m on treadmill test (5% slope, 3 km/hr) were randomized to 4 weeks of double-blind treatment either with 60 mcg PGE1 daily given IV in 250 mL saline over a period of 2 hours (21 patients) or placebo (250 mL saline, 21 patients). Treatment-free follow-up was completed 8 weeks after the final infusion. Pain free walking distance (PFWD), MWD, and questionnaire evaluation were determined at baseline, after the 4-week treatment period, and at the end of the 8 weeks of the treatment-free follow-up period. After 4 weeks of treatment with PGE1 PFWD and MWD increased from 72 +/- 16 m to 135 +/- 33 m (+87%, p<0.001)and from 140 +/- 30 m to 266 +/- 62 m (+90%, p<0.001), respectively. Analysis of the Walking Impairment Questionnaire responses in the PGE1 group at 4 weeks demonstrated significant improvements in the walking impairment score (+19 percentage points, p<0.001), in the distance score (+25 percentage points, p<0.001), in the speed score (+24 percentage points, p<0.001), in the stair climbing score (+20 percentage points, p<0.001). The RAND survey responses showed improvements in physical function and bodily pain scores (+14 percentage points, p<0.001, and +15 percentage points, p<0.01, respectively). After the treatment-free follow-up period of 8 weeks, increases in PFWD and MWD were maintained (113 +/- 26 m, +57%, p<0.001, and 229 +/- 55 m, +63%, p<0.001, respectively). Similarly, at the end of the treatment-free follow-up, the walking impairment score (+16 percentage points, p<0.001), the distance score (+23 percentage points, p<0.001), the speed score (+22 percentage points, p<0.001), the stair climbing score (+18 percentage points, p<0.001) as well as the RAND physical function and bodily pain scores (+10 percentage points, p<0.001, and +13 percentage points, p<0.01, respectively) were still increased compared with baseline. No change from baseline was found in all the target parameters in the placebo group after 4 weeks of treatment and at the end of the treatment-free follow-up period. These data show that a 4-week treatment with PGE1 improves functional status and quality of life as well as treadmill performance in patients with disabling intermittent claudication as compared with placebo-treated patients. The improvements are also maintained for a period of 8 weeks beyond the end of the treatment. Additional studies are needed to determine the duration of functional benefits after the end of treatment. Twenty-six patients with severe short-distance claudication underwent a 24-week, randomized, double-blind, parallel-group evaluation of the efficacy of pentoxifylline in the treatment of intermittent claudication. The primary variables analyzed were the initial and absolute claudication distances as determined by standardized treadmill walking. A statistically significant improvement in both parameters was present in the pentoxifylline-treated patients. Nausea was the only drug side effect noted. The efficacy, safety, and tolerance of pentoxifylline (Trental, Hoechst-Roussel Pharmaceuticals, Inc.) in the treatment of intermittent claudication associated with chronic occlusive arterial disease (COAD) were evaluated in a double-blind, placebo-controlled, parallel-group, multicenter clinical trial involving a total of 128 outpatients. The response to treatment was ascertained at regular intervals during the trial by measuring the distance walked prior to the onset of claudication when patients were subjected to a standardized treadmill test. Pentoxifylline given orally in doses up to 1200 mg/day was significantly more effective than placebo in increasing both the initial and absolute claudication distances in patients with COAD. Reduction of lower limb paresthesias also suggested greater clinical improvement in the pentoxifylline treated patients. These results support the hypothesis that pentoxifylline reduces blood viscosity by improving red cell flexibility, and thereby enhances blood flow in patients with COAD. White the precise mode of therapeutic action requires clarification, pentoxifylline was well tolerated with minimal unwanted effects. Aim of the study is to evaluate the effects of Prostaglandin E-1 (PGE-1) in patients with peripheral arterial disease (PAD) at the 2nd b stage Fontaine's classification. The study, controlled, single blinded, enrolled 123 patients with intermittent claudication that were randomised in two groups; the first group received a treatment with PGE-1 while the second one received a pentoxifylline-buflomedil association by venous infusion. We evaluated: Pain Free Walking Distance (PFWD), Maximum Walking Distance (MWD), Rest Flow (RF), Peak Flow (PF), Basal (BVR) and Minimal Vascular Resistance (MVR) with a strain gauge plethysmograph, Resting Flow (RF), Peak Flow (PF), time to reach the Peak Flow (tPF) and time to recovery of the base values (tRF) with laser Doppler flowmeter. After a four weeks treatment, we observed an increase of 370% about PFWD and of 260% in the MWD in patients treated with PGE-1; the other group showed an increase of 110% and 118% respectively. Moreover, the patients of the first group showed a significant increase regarding the plethysmographic Peak Flow (from 9.75+/-1.37 to 16.21+/-1.75, p<0.001), greater than the one observed in the second group (from 9.53+/-1.41 to 13.47+/-1.53, p<0.05); also the laser Doppler parameters showed a significant reduction, more evident in the first group (tPF from 23.0+/-7.5 to 10.5+/-4.9, p<0.001; tRF from 73.5+/-22.7 to 48.3+/-13.5, p<0.001) than in the second one. to compare the effect of surgery, exercise and simple observation on maximum exercise power in claudicants. Design: prospective, randomised study.
                a total of 264 unselected claudicants were randomised to supervised exercise training, invasive treatment (open surgical or endovascular procedures) or observation. One year treatment outcomes were analysed on an intention to-treat basis.
                invasively treated patients showed a significant improvement in maximum walking power, stopping distance, post-ischaemic blood flow and big toe pressure at one year. Patients randomised to physical exercise training or to the control group did not improve in any outcome measure.
                invasive treatment increased walking capacity, leg blood pressure and flow. Supervised physical exercise training offered no therapeutic advantage compared to untreated controls.
                Copyright 2001 Harcourt Publishers Limited. Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. This study was undertaken to investigate the long-term effects of policosanol administered to patients with moderately severe intermittent claudication. The study consisted of a 6-week single-blind, placebo-controlled run in phase, followed by a 2-year double-blind, randomized treatment step. Fifty-six patients who met study entry criteria were randomized to receive placebo or policosanol 10 mg twice daily. Walking distances on a treadmill (constant speed 3.2 km/h, slope 10 degrees, temperature 25 degrees C) were assessed before and after 6, 12, 18, and 24 months of treatment. Both groups were similar at randomization. After 6 months of therapy, policosanol significantly increased (p < 0.01) the initial claudication distance from 125.9 +/- 8.7 m to 201.1 +/- 24.8 m and the absolute claudication distance from 219.5 +/- 14.1 m to 380.7 +/- 50.2 m. Both variables remained unchanged in the placebo group (p < 0.01). These effects did not wear off but improved after long-term therapy, so that final values were 333.5 +/- 28.6 m (initial claudication distance) and 648.9 +/- 54.1 m (absolute claudication distance); both significantly greater (p < 0.0001) than those obtained in the placebo group, which showed values of 137.9 +/- 21.8 m (initial claudication distance) and 237.7 +/- 28.1 m (absolute claudication distance), respectively. At study completion, 21 policosanol and 5 placebo patients attained increases in claudication distance values > 50% (p < 0.001). Policosanol, but not placebo, significantly increased the ankle/arm pressure index. In addition, from month 6 up to study completion, the frequency of patients reporting improvement of lower limb symptoms was greater in the policosanol group than in the placebo group. The treatment was tolerated well. There were 16 withdrawals (12 placebo, 4 policosanol) from the study. Eight patients in the placebo group experienced a total of 10 serious adverse events, 8 of which were vascular events, compared with none in the policosanol group (p < 0.01). In addition, 3 patients in the policosanol group and 3 patients in the placebo group reported mild adverse events during the study. The present results demonstrate the long-term usefulness of policosanol therapy to treat patients with intermittent claudication. Intermittent claudication due to peripheral arterial occlusive disease (PAOD) is a common cause of pain and disability in the middle-aged. Clinical trials of the potent vasodilator prostaglandin E1 have been disappointing. This is the first report of a controlled clinical trial of AS-0:3, a novel prodrug of prostaglandin E1 incorporated into lipid microspheres that has been developed to improve delivery of the active compound to blood vessel walls.
                Eighty patients with stenosis or occlusion, symptoms of intermittent claudication, and maximum walking distance of > or = 30 and < or = 300 m on a standard treadmill test were randomized to placebo or one of three dosage regimens of AS-013. Drug was administered by intravenous injection 5 d/wk for 4 weeks. Treadmill tests and other assessments were completed at weeks 0, 4, and 8. A statistically significant increase in maximum walking distance was observed at 4 weeks (for placebo: median, 4.5 m; interquartile range [IQR], 20; for active treatment: median, 28.0 m; IQR, 81; P < .01, Mann-Whitney test). A similar response was seen at 8 weeks (for placebo; median, -11.2 m; IQR, 35; for active treatment: median, 35 m; IQR, 68; P < .01, Mann-Whitney test). Dose-related improvements in pain-free walking distance and quality of life were observed. No serious safety issues were noted.
                These promising clinical data indicate that AS-013, a new prodrug of prostaglandin E1, could provide an effective and acceptable treatment for patients with intermittent claudication. Studies to investigate the optimal dosing regimen, duration of clinical benefit, and effects in more severe forms of peripheral arterial disease are warranted. A double-blind, randomized multicentre study was undertaken to evaluate the possible effect of chelation treatment with ethylenediamine-tetraacetic acid (EDTA) in patients with severe intermittent claudication. A total of 153 patients received 20 intravenous infusions of either 3 g Na2EDTA or placebo during a period of 5-9 weeks. Vitamin, mineral and trace element supplements were administered orally. The changes observed in the pain-free and maximal walking distances, measured on a treadmill, were similar in the two groups. During the 3-month (n = 149) and 6-month (n = 123) follow-up period, no long-term therapeutic effect of EDTA could be demonstrated. The ankle-brachial blood pressure index remained unchanged throughout the study period. This study failed to demonstrate any effect of EDTA chelation treatment in intermittent claudication. It has been shown that the antiprogestin RU 486 (mifepristone) increases the sensitivity of the early pregnant human uterus to the stimulatory action of synthetic prostaglandin E (PGE) analogues. To examine if RU 486 also increases uterine sensitivity to the naturally occurring PGE2 given orally, two investigative approaches were used in the present studies: (i) direct registration of uterine contractions before and after PGE2 administration in untreated and RU 486-treated early pregnant women; and (ii) a double-blind, randomized, controlled efficacy trial involving treatment of pregnant women (amenorrhoea of less than or equal to 49 days) with RU 486 (25 mg twice daily for 4 days) and PGE2 (1 mg once or twice) or placebo on the last day of RU 486 treatment. The results indicate that oral PGE2 at the doses employed had little or no stimulatory effect on uterine contractility and that it did not improve the rate of complete abortion achieved with RU 486 alone. Overall, 25 of 42 women (59%) had a complete abortion, 15 women (36%) did not abort and the remaining two had incomplete abortions. Women with complete abortions had significantly lower pretreatment levels of progesterone and a longer duration of induced bleeding than those who did not abort. Thus oral PGE2, when given in clinically acceptable doses, is not a suitable alternative to synthetic PGE analogues for use in combination with RU 486 for termination of early pregnancy. The authors conducted a prospective, randomized, double-blinded clinical trial for the purpose of elucidating the effects of prostaglandin E1 (PGE1) on idiopathic sudden sensorineural hearing loss.
                With the approval of the institute ethics committee, a total of 57 consecutive patients with diagnoses of idiopathic sudden sensorineural hearing loss were included in the study. The patients in the PGE1 group received continuous infusion containing 60 microg PGE1 and 100 mg hydrocortisone for 7 days, and the patients in the placebo group were treated with continuous infusion containing an inactive placebo and 100 mg hydrocortisone.
                No significant differences were observed in the improvements of pure-tone average and subjective symptoms between the PGE1 and the placebo groups. However, the hearing improvement at high frequencies (4 kHz and 8 kHz) was significantly higher in the PGE1 group than in the placebo group, especially in the patients with severe tinnitus.
                These results failed to prove a beneficial effect of PGE1 in the treatment of idiopathic sudden sensorineural hearing loss. Further studies will be needed to clarify the pharmacologic actions of PGE1 in the cochlea. Twenty-seven children with perennial rhinitis entered a double-blind cross-over study comparing nasal sprays of flunisolide---a new topical corticosteroid---and placebo. Symptoms were assessed over two consecutive monthly periods with each treatment. Weekly diary cards, monthly clinical assessments, and end-of-trial preferences all favoured the active drug. At the end of the trial 20 patients preferred the treatment month with flunisolide, four preferred the placebo month, and two rated the periods equally. Side effects were mild, the commonest being transient nasal stinging. Seventeen children who derived benefit from flunisolide continued with the treatment for a six-month open-study period. Many reduced the dosage from three times to twice or once daily without losing benefit. The effect of flunisolide on the pituitary-adrenal axis was assessed in seven children by measuring the 0900 blood cortisol concentrations at two-month intervals over the six months. No effect was observed. The results show that flunisolide is effective and safe for the treatment and prophylaxis of perennial rhinitis in children. Prostaglandin E1 (PGE1) was compared to placebo in a 100-patient (50 PGE1, 50 placebo) randomized, double-blind, clinical trial to determine whether PGE1 therapy enhances survival of patients with adult respiratory distress syndrome (ARDS) when infused through a central line at 30 ng/kg/min continuously for seven days. At 30 days postinfusion, 30 PGE1 and 24 placebo patients had died. Total deaths judged to be related to the syndrome were 32 and 28 in the PGE1 and placebo groups respectively at six months. We conclude that PGE1 did not enhance survival in patients with established ARDS. PGE1 augmented the hyperdynamic circulation of these patients by reducing systemic and pulmonary vascular resistance, which resulted in a reduction of blood pressures and increased stroke volume, cardiac output, and heart rate. An improvement in oxygen availability and oxygen consumption was observed with PGE1 therapy. PGE1 was associated with an increased incidence of diarrhea (six patients in the PGE1 group vs one in the placebo group, p less than 0.05). Other adverse effects included hypotension (ten patients in the PGE1 group vs seven in the placebo group), fever (six patients in the PGE1 group vs three in the placebo group), and non-fatal dysrhythmias (ten in the PGE1 group vs five in the placebo group).
Whilst results from some individual studies suggested a beneficial effect of PGE1, the quality of these studies and of the overall evidence available is insufficient to determine whether or not patients with intermittent claudication derive clinically meaningful benefit from the administration of prostanoids. Further well-conducted randomised, double blinded trials with a sufficient number of participants to provide statistical power are required to answer this question.