Long-term treatment of asthmatic patients with salmeterol vs slow-release theophylline. Salmeterol vs theophylline: sleep and efficacy outcomes in patients with nocturnal asthma. [Therapy of nocturnal asthma: salmeterol versus nocturnal administration of retard theophylline--comparison of effectiveness and tolerance]. The salmeterol/fluticasone combination is more effective than fluticasone plus oral montelukast in asthma. The efficacy and tolerability of inhaled salmeterol and individually dose-titrated, sustained-release theophylline in patients with reversible airways disease. Nocturnal asthma: effect of salmeterol on quality of life and clinical outcomes. Efficacy of inhaled salmeterol in the management of smokers with chronic obstructive pulmonary disease: a single centre randomised, double blind, placebo controlled, crossover study. Comparison of inhaled salmeterol and individually dose-titrated slow-release theophylline in patients with reversible airway obstruction. European Study Group. Addition of inhaled salmeterol to inhaled corticosteroids in patients with poorly controlled nocturnal asthma. [Efficacy of and tolerance to salmeterol compared to salbutamol in patients with bronchial asthma].
The aim of the present multicentre, open, randomized, parallel group study was to evaluate the efficacy and safety of salmeterol versus theophylline in asthmatic patients. A total of 112 patients were randomized: 56 received inhaled salmeterol (50 micrograms twice daily) and 50 oral dose titrated theophylline twice daily. The study lasted 12 months. The efficacy of both drugs was evaluated for the first 3 months of the study and the safety for a further 9 months. Spirometric measurements were carried out for the total duration of the study. Salmeterol showed a greater and more significant efficacy than theophylline in reducing both day- and night-time symptoms (P < 0.001) and in reducing additional salbutamol requirement (P < 0.001). The subjective assessment of efficacy by physicians and patients was in favour of salmeterol from the first month of treatment (P < 0.001). Both drugs improved the quality of life as measured by the specific questionnaire 'Living with Asthma' with no significant differences. The total number of adverse events was slightly higher in the theophylline group compared with salmeterol (18 vs 9; P n.s.). Both salmeterol and theophylline increased morning and evening PEFR with no significant difference. FEV1 and FVC increased in both groups of patients; the difference between the effects of the two treatment was not statistically significant at 12 months. Our study suggests that salmeterol has higher efficacy and safety than theophylline in long-term treatment of asthmatic patients. To compare the efficacy, safety, and effects on sleep quality of salmeterol and extended-release theophylline in patients with nocturnal asthma.
                Randomized, double-blind, double-dummy, three-period crossover.
                Outpatients at a single center. Patients spent 1 night during screening and 2 nights during each study period in a sleep laboratory for completion of sleep studies.
                Male and female patients who were at least 18 years old with nocturnal asthma (baseline FEV1, 50 to 90% of predicted) and who required regular bronchodilator therapy. Patients on inhaled corticosteroids, cromolyn, and nedocromil were allowed into the study if their dosing remained constant throughout the study.
                Inhaled salmeterol (42 microg per actuation), extended-release oral theophylline (titrated to serum levels of 10 to 20 microg/mL), and placebo taken twice daily.
                Efficacy measurements included nocturnal spirometry, nocturnal polysomnography, sleep questionnaires, and daily measurements of lung function and symptoms. Salmeterol was superior to theophylline (p < or = 0.05) in maintaining nocturnal FEV1 levels and was superior to placebo (p < or = 0.05) in improving morning and evening peak expiratory flow (PEF) and in decreasing nighttime albuterol use. The use of salmeterol significantly increased the percentage of days and nights with no albuterol use and decreased daytime albuterol use compared with theophylline and placebo (p < or = 0.05). Sleep quality global scores significantly improved with salmeterol and placebo (p < 0.001) but not with theophylline. The effects on sleep architecture were similar across treatment groups.
                Salmeterol (but not theophylline) was associated with sustained improvements in morning PEF, protection from nighttime lung function deterioration, reductions in albuterol use, and improvements in patient perceptions of sleep. No differences were seen in polysomnographic measures of sleep quality. The aim of the present study was to compare the efficacy and the tolerability of salmeterol and theophylline in patients with nocturnal asthma. 16 patients were entered into a randomized, double-blind, crossover trial. Using a double-dummy technique, salmeterol (50 micrograms b.i.d. by MDI) or theophylline (Uniphyllin; 600 mg nocte orally) were given for periods of 7 days with a wash-out period of 7 days between treatment periods. With salmeterol the number of nights with an overnight fall in peak expiratory peak flow rate (PEFR) of at least 20% was reduced by about 20% compared to about 10% with theophyllin (p < 0.05 for the difference between salmeterol and theophylline). With respect to nocturnal symptoms 62.6% of the patients had rare or non symptoms without and 84.7% with salmeterol, compared to 46.5% without and 67.3% with theophylline (p < 0.05). With respect to the improvement of early morning symptoms, the increase of nights with none or rare symptoms was 46.2% with salmeterol compared to 25.8% with theophylline. The overall parameter of efficacy defined as a) the number of nights with an overnight fall in PEFR or less than 20% als well as b) none or rare nocturnal symptoms and c) none or rare early morning symptoms increased from 23.4% at baseline to 75.1% during treatment with salmeterol compared to an increase from 24.5% at baseline with 54.8% during treatment with theophylline (p < 0.05). 12 patients preferred salmeterol over theophylline (p < 0.05). 3 patients had gastrointestinal disturbances during theophylline treatment. It can be concluded that both salmeterol and theophylline are effective in the treatment of nocturnal asthma. With respect to the overall efficacy and the tolerability salmeterol is superior to theophylline. The aim of this study was to compare the efficacy and safety of salmeterol/fluticasone propionate combination product (SFC) with fluticasone propionate (FP) plus oral montelukast (M) over 12 weeks in symptomatic asthma patients. The study was a multinational, randomised, double-blind, double-dummy, parallel-group design in patients aged > or = 15 years. After a 4-week run-in during which all patients received FP 100 microg twice daily, patients were randomised to inhaled SFC (50/100 microg) twice daily or inhaled FP 100 microg twice daily and oral M 10 mg once daily. Patients kept daily records of their peak expiratory flow (PEF) symptom scores and use of rescue medication. Over the 12-week treatment period, the adjusted increase in mean morning PEF was significantly greater in the SFC group (36 l/min) than the FP/M group (19 l/min; P < 0.001). The improvement in FEV1 was also significantly greater in the SFC group (mean treatment difference 0.11 l; P < 0.001). SFC provided significantly better control of daytime and night-time symptoms and there were fewer exacerbations. Patients in the SFC group were also significantly more likely to have a rescue-free day. Both treatments were equally well tolerated. Combination therapy with FP plus salmeterol (SFC) produced significantly greater improvements in lung function and asthma control than the addition of montelukastto FP. In a double-blind, double-dummy, cross-over, multicentre study, 141 patients with moderate reversible airways disease were randomized to receive either 50 micrograms salmeterol via a metered dose inhaler or individually dose-titrated oral theophylline, both twice daily for a 2-week period. Just over half (n = 77) the patients had received theophylline before, but 64 patients were new to theophylline therapy. Efficacy was based on lung function data and symptom scores. Salmeterol produced significantly higher increase in mean morning peak expiratory flow (PEF) of 161 min-1 (P < 0.001; 95% Confidence Interval (CI); 8-241 min-1) and mean evening PEF of 151 min-1 (p < 0.001; 95% CI; 7-221 min-1) compared with theophylline therapy. Further analysis of the data revealed that the increase in PEF with salmeterol compared with theophylline was highest in a sub-group of patients new to theophylline therapy. Patients on salmeterol had significantly less night-time awakenings than those on theophylline (P = 0.011) and significantly less daytime symptoms (P = 0.017). There was also a significant increase in the number of nights (P = 0.013) and days (P < 0.001) on salmeterol when no additional salbutamol was required compared with theophylline. Theophylline produced a higher incidence of adverse events compared with salmeterol. The results of this study show that inhaled salmeterol is more effective and better tolerated than individually dose-titrated oral theophylline over a 2-week study period in patients with moderate asthma. To evaluate the effect of salmeterol on asthma-specific quality of life in patients experiencing significant nocturnal symptoms.
                Randomized, double-blind, placebo-controlled, multicenter clinical trial.
                Allergy/respiratory care clinics.
                Nonsmokers > or = 12 years of age with nocturnal asthma symptoms on at least 6 of 14 days during screening and > or = 15% decrease in peak expiratory flow (PEF) from baseline on nocturnal awakening at least once during screening.
                Salmeterol, 42 microg, or placebo twice daily. Patients were allowed to continue theophylline, inhaled corticosteroids, and "as-needed" albuterol.
                Outcome measures included Asthma Quality of Life Questionnaire (AQLQ) global and individual domain scores, FEV1, PEF, nighttime awakenings, asthma symptoms, and supplemental albuterol use. Mean change from baseline for the global and domain AQLQ scores was significantly greater (p < or = 0.005) with salmeterol compared with placebo. At week 12, salmeterol significantly (p < 0.001 compared with placebo) increased mean change from baseline in FEV1, morning and evening PEF, percentage of symptom-free days, percentage of nights with no awakenings due to asthma, and the percentage of days and nights with no supplemental albuterol use. Significant improvements in PEF were observed after treatment with salmeterol regardless of concomitant treatment with theophylline (p < 0.05).
                These results provide evidence that validates the role of salmeterol in improving quality of life in patients with moderate persistent asthma who exhibited nocturnal asthma symptoms and supports the efficacy of salmeterol compared with that of placebo (ie, "as-needed" albuterol). The acute response to bronchodilators in patients with chronic obstructive pulmonary disease (COPD) is modest; it has, however, been suggested that these patients may benefit from long term treatment.
                To investigate the efficacy of salmeterol in smokers with moderate to severe COPD a double blind, randomised, crossover comparison was performed between salmeterol (50 micrograms twice daily) and placebo in 63 patients with stable COPD (mean age 65 years). Prior to inclusion, all patients had a forced expiratory volume in one second (FEV1) of < 60% of predicted and an improvement in FEV1 of < 15% following 400 micrograms inhaled salbutamol. Patients received four weeks of therapy with each of the treatment regimens. Assessment of efficacy was made with recording of morning and evening peak expiratory flow rates (PEF), respiratory symptoms, and use of rescue salbutamol. FEV1 was measured before and after nebulised salbutamol prior to randomisation and at the end of each treatment period.
                Morning PEF values were higher during the salmeterol than during the placebo period, although the mean treatment difference was small (12 l/min (95% confidence limits 6 to 17)). No difference in mean evening PEF values was found. Diurnal variation in PEF, assessed as the difference between the morning PEF and that of the previous evening, was more pronounced during the placebo than during the salmeterol period. The mean spirometric values (including reversibility in FEV1) obtained at the end of the two treatment periods were similar. Compared with placebo, treatment with salmeterol was associated with lower daytime and night time symptom scores and less use of rescue salbutamol both during the day and the night. The patients rated the treatment with salmeterol better than treatment with placebo.
                This study shows that, compared with placebo, treatment with salmeterol produces an improvement in respiratory symptoms and morning PEF values in patients with moderate to severe COPD. Treatment with long acting beta agonists may therefore result in an improvement in functional status, even in patients suffering from apparently nonreversible obstructive pulmonary disease. The aim of this study was to compare the clinical efficacy of salmeterol versus theophylline in the treatment of moderate-to-severe asthma. One hundred and eighty nine asthmatic patients (forced expiratory volume in one second (FEV1) or peak expiratory flow (PEF) >50% of predicted) were randomized to receive either salmeterol dry powder, 50 microg b.i.d. via a Diskhaler (n=92) or dose-titrated slow-release theophylline capsules ("Theo-Dur") b.i.d. (n=97), in a double-blind, double-dummy, parallel group study for 4 weeks. Patients had previously been titrated with theophylline to a serum theophylline level of 10-20 microg x mL-1. The median percentage of nights with no asthma symptoms rose from 14% in both groups at baseline to 71% with salmeterol and to 46% with theophylline (p=0.044). There was also a significant increase for salmeterol in the median percentage of nights with no rescue salbutamol use (from 36 to 86%) compared with theophylline (from 71 to 78%; p=0.002). The mean morning PEF increased from 337 L x min-1 in the salmeterol group and 332 L x min-1 in the theophylline group to 372 and 357 L x min-1, respectively. No significant difference between the two treatments was observed for PEF, symptoms or additional salbutamol medication during the day. The incidence of gastrointestinal symptoms (gastric irritation, nausea and vomiting) was greater among patients receiving theophylline (11%) than with salmeterol (3%). These findings suggest that inhaled salmeterol is more effective in relieving symptoms of asthma, and better tolerated than theophylline in patients with moderate-to-severe asthma. The effect of adding inhaled salmeterol to inhaled corticosteroids was studied in patients with poorly controlled nocturnal asthma. In a double-blind, cross-over study, 20 patients were randomized to receive either salmeterol 50 micrograms twice daily or placebo via a Diskhaler after a 1-week run-in period. After 4 weeks of treatment, patients were subsequently crossed over to receive the other treatment for a further 4 weeks with a 2-week wash-out period in between. The response to treatment was assessed by peak expiratory flow rates (PEF) measured in the morning and evening, symptom scores of asthma, number of bronchodilators used, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at regular intervals. Patients' preference for the Diskhaler or metered-dose inhaler was assessed at the last visit. The results showed that morning PEF was significantly higher while on salmeterol than on placebo (296.9 +/- 70.2 vs 274.6 +/- 77.4 L/min). Evening PEF showed a trend towards a higher value while on salmeterol than on placebo (321.1 +/- 73.4 vs 288.7 +/- 79.4 L/min), but the difference was not significant. There was no statistically significant improvement in symptom scores, number of rescue bronchodilators used and FEV1 or FVC between the two treatment groups. The occurrence of side effects in terms of tremors and palpitations between treatment and placebo were similar. There were more patients who preferred Diskhaler to metered-dose inhaler (70% vs 30%). We conclude that salmeterol 50 micrograms twice daily produces significant improvement in morning PEF and is well tolerated in patients with nocturnal asthma. Diskhaler is a device which is easy to use and preferred to a metered-dose inhaler. Beta 2-agonists are considered one of the cornerstones of the asthma therapy, but their short action requires frequent administration and an association with other broncodilators. The development of long-acting beta 2-agonists may represent an important improvement in asthma treatment.
                The present study was designed to assess the efficacy and safety of inhaled salmeterol compared to salbutamol in patients with mild-to-moderate asthma.
                After the two run-in weeks, the patients received either salmeterol 50 mg twice a day or salbutamol 200 mg four times a day, over a four week period, following a double blind, parallel group study. Sixty patients had the following inclusion criteria: FEV1 > 50% or PEFR over the past seven days > 50% of predicted normal; reversibility of FEV1 > 15%; symptoms scores > 2 (score 0 and 5) in 4 of the last seven days or PEFR variation > 15%.
                Seven patients discontinued the protocol (see methods). Of the 53 analyzable patients, 25 were of the salmeterol group and 28 of the salbutamol group. Our results showed that in the run-in period there were not differences among the groups comparing the values of FEV1 in % predicted, morning PEFR and asthma symptoms scores. The improvement rate of morning FEV1 and PEFR in patients who received salmeterol was significantly higher (p < 0.05) compared to the patients who received salbutamol, for two and four weeks of treatment. Also, the salmeterol group have shown reduction of the symptoms in the nocturnal period(significantly in the first fortnight of treatment) demonstrated by the significative increase in the symptoms improvement rate when compared salmeterol and to salbutamol groups. The number of rescue medication inhaled, side effects, heart rate, blood pressure, serum potassium dosage and electrocardiograms, did no show significative differences between the groups.
                This study showed that in mild to moderate asthmatic patients, salmeterol in the dosage of 100 mg/day raised the FEV1 and the morning PEF and led to pronounced decrease in the nocturnal symptoms as compared to salbutamol. The side effects were similar.
Long-acting beta-2 agonists, particularly salmeterol, are more effective than theophylline in improving morning and evening PEF, but are not significantly different in their effect on FEV1. There is evidence of decreased daytime and nighttime short-acting beta-2 agonist requirement with salmeterol. Fewer adverse events occurred in participants using long-acting beta-2 agonists (salmeterol and formoterol) as compared to theophylline.