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Study objective To compare the safety of salmeterol xinafoate or placebo added to usual asthma care. Design A 28-week, randomized, double-blind, placebo-controlled, observational study. Setting Study subjects were seen once in the study physician's office for screening and were provided all blinded study medication for the entire study period. Follow-up by telephone was scheduled every 4 weeks. Participants Subjects (> 12 years old) with asthma as judged by the study physician were eligible. Individuals with a history of long-acting β2-agonist use were excluded. Interventions Salmeterol, 42 μg bid via metered-dose inhaler (MDI), and placebo bid via MDI. Measurements and results Following an interim analysis in 26,355 subjects, the study was terminated due to findings in African Americans and difficulties in enrollment. The occurrence of the primary outcome, respiratory-related deaths, or life-threatening experiences was low and not significantly different for salmeterol vs placebo (50 vs 36; relative risk [RR] = 1.40; 95% confidence interval [CI], 0.91 to 2.14). There was a small, significant increase in respiratory-related deaths (24 vs 11; RR, 2.16; 95% CI, 1.06 to 4.41) and asthma-related deaths (13 vs 3; RR, 4.37; 95% CI, 1.25 to 15.34), and in combined asthma-related deaths or life-threatening experiences (37 vs 22; RR, 1.71; 95% CI, 1.01 to 2.89) in subjects receiving salmeterol vs placebo. The imbalance occurred largely in the African-American subpopulation: respiratory-related deaths or life-threatening experiences (20 vs 5; RR, 4.10; 95% CI, 1.54 to 10.90) and combined asthma-related deaths or life-threatening experiences (19 vs 4; RR, 4.92; 95% CI, 1.68 to 14.45) in subjects receiving salmeterol vs placebo. Conclusions For the primary end point in the total population, there were no significant differences between treatments. There were small, but statistically significant increases in respiratory-related and asthma-related deaths and combined asthma-related deaths or life-threatening experiences in the total population receiving salmeterol. Subgroup analyses suggest the risk may be greater in African Americans compared with Caucasian subjects. Whether this risk is due to factors including but not limited to a physiologic treatment effect, genetic factors, or patient behaviors leading to poor outcomes remains unknown.

Background Asthma and allergic rhinitis are both highly prevalent diseases and often coexist in patients. Objective To investigate the effect of rhinitis therapy on asthma outcomes in adult and adolescent patients with both seasonal allergic rhinitis (SAR) and persistent asthma. Methods A total of 863 patients (mean baseline FEV 1 81% predicted) were randomized to receive open-label fluticasone propionate/salmeterol (FSC), 100/50 μg bid for 4 weeks, plus either blinded fluticasone propionate aqueous nasal spray (FPANS) 200 μg/d, montelukast 10 mg/d, or placebo. Patients kept daily records of peak expiratory flow (PEF), asthma, and rhinitis symptoms and rescue albuterol use. Results FPANS added to FSC resulted in superior outcomes for daytime total nasal symptom scores (D-TNSS) and individual daytime nasal specific symptoms (congestion, rhinorrhea, sneezing, and itching) compared with montelukast plus FSC and placebo plus FSC (p ≤ 0.001). Montelukast plus FSC was superior to placebo plus FSC only for D-TNSS and itching and sneezing. Morning PEF, asthma symptoms, and rescue albuterol use improved significantly (p ≤ 0.001) in all treatment groups, but improvements were comparable across the treatment groups. Conclusion In patients with persistent asthma treated with FSC, the addition of montelukast or FPANS for the treatment of SAR resulted in no additional improvements in overall asthma control compared with FSC alone. However, FPANS provided superior rhinitis control compared with montelukast. These data suggest that asthma and rhinitis should each be optimally treated.

Study objectives: Comparison of inhaled salmeterol powder vs oral montelukast treatment in patients with persistent asthma who remained symptomatic while receiving inhaled corticosteroids. Design: Randomized, double-blind, double-dummy, parallel-group, multicenter trials of 12-week duration. Setting: Outpatients in private and university-affiliated clinics. Patients: Male and female patients > 15 years of age with a diagnosis of asthma (baseline FEV1 of 50 to 80% of predicted) and symptomatic despite receiving inhaled corticosteroids. Interventions: Inhaled salmeterol xinafoate powder, 50 mg bid, or oral montelukast, 10 mg qd. Measurements and results: Treatment with salmeterol powder resulted in significantly greater improvements from baseline compared with montelukast for most efficacy measurements, including morning peak expiratory flow (35.0 L/min vs 21.7 L/min; p < 0.001), percentage of symptom-free days (24% vs 16%; p < 0.001), and the percentage of rescue-free days (27% vs 20%; p 5 0.002). Total supplemental albuterol use was decreased significantly more in the salmeterol group compared with the montelukast group (2 1.90 puffs per day vs 2 1.66 puffs per day; p 5 0.004) and nighttime awakenings per week decreased significantly more with salmeterol than with montelukast (2 1.42 vs 2 1.32; p 5 0.015). Patients treated with inhaled salmeterol were significantly more satisfied with their treatment regimen and how well, how fast, and how long it worked than were patients who were treated with oral montelukast. The safety profiles for the two treatments were similar. Conclusion: In patients with persistent asthma who remain symptomatic while receiving inhaled corticosteroids, adding inhaled salmeterol powder provided significantly greater improvement in lung function and asthma symptoms and was preferred by patients over oral montelukast. (CHEST 2001; 120:423‐430)

Study objectives To compare the efficacy, safety, and effects on sleep quality of salmeterol and extended-release theophylline in patients with nocturnal asthma. Design Randomized, double-blind, double-dummy, three-period crossover. Setting 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. Patients Male and female patients who were at least 18 years old with nocturnal asthma (baseline FEV 1 , 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. Interventions Inhaled salmeterol (42 μg per actuation), extended-release oral theophylline (titrated to serum levels of 10 to 20 μg/mL), and placebo taken twice daily. Measurements and results Efficacy measurements included nocturnal spirometry, nocturnal polysomnography, sleep questionnaires, and daily measurements of lung function and symptoms. Salmeterol was superior to theophylline (p ≤ 0.05) in maintaining nocturnal FEV 1 levels and was superior to placebo (p ≤ 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 ≤ 0.05). Sleep quality global scores significantly improved with salmeterol and placebo (p Conclusions 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.

To compare the safety of salmeterol xinafoate or placebo added to usual asthma care.A 28-week, randomized, double-blind, placebo-controlled, observational study.Study subjects were seen once in the study physician's office for screening and were provided all blinded study medication for the entire study period. Follow-up by telephone was scheduled every 4 weeks.Subjects (12 years old) with asthma as judged by the study physician were eligible. Individuals with a history of long-acting beta2-agonist use were excluded.Salmeterol, 42 mug bid via metered-dose inhaler (MDI), and placebo bid via MDI.Following an interim analysis in 26,355 subjects, the study was terminated due to findings in African Americans and difficulties in enrollment. The occurrence of the primary outcome, respiratory-related deaths, or life-threatening experiences was low and not significantly different for salmeterol vs placebo (50 vs 36; relative risk [RR] = 1.40; 95% confidence interval [CI], 0.91 to 2.14). There was a small, significant increase in respiratory-related deaths (24 vs 11; RR, 2.16; 95% CI, 1.06 to 4.41) and asthma-related deaths (13 vs 3; RR, 4.37; 95% CI, 1.25 to 15.34), and in combined asthma-related deaths or life-threatening experiences (37 vs 22; RR, 1.71; 95% CI, 1.01 to 2.89) in subjects receiving salmeterol vs placebo. The imbalance occurred largely in the African-American subpopulation: respiratory-related deaths or life-threatening experiences (20 vs 5; RR, 4.10; 95% CI, 1.54 to 10.90) and combined asthma-related deaths or life-threatening experiences (19 vs 4; RR, 4.92; 95% CI, 1.68 to 14.45) in subjects receiving salmeterol vs placebo.For the primary end point in the total population, there were no significant differences between treatments. There were small, but statistically significant increases in respiratory-related and asthma-related deaths and combined asthma-related deaths or life-threatening experiences in the total population receiving salmeterol. Subgroup analyses suggest the risk may be greater in African Americans compared with Caucasian subjects. Whether this risk is due to factors including but not limited to a physiologic treatment effect, genetic factors, or patient behaviors leading to poor outcomes remains unknown.

Asthma and allergic rhinitis are both highly prevalent diseases and often coexist in patients.To investigate the effect of rhinitis therapy on asthma outcomes in adult and adolescent patients with both seasonal allergic rhinitis (SAR) and persistent asthma.A total of 863 patients (mean baseline FEV1 81% predicted) were randomized to receive open-label fluticasone propionate/salmeterol (FSC), 100/50 microg bid for 4 weeks, plus either blinded fluticasone propionate aqueous nasal spray (FPANS) 200 microg/d, montelukast 10 mg/d, or placebo. Patients kept daily records of peak expiratory flow (PEF), asthma, and rhinitis symptoms and rescue albuterol use.FPANS added to FSC resulted in superior outcomes for daytime total nasal symptom scores (D-TNSS) and individual daytime nasal specific symptoms (congestion, rhinorrhea, sneezing, and itching) compared with montelukast plus FSC and placebo plus FSC (por = 0.001). Montelukast plus FSC was superior to placebo plus FSC only for D-TNSS and itching and sneezing. Morning PEF, asthma symptoms, and rescue albuterol use improved significantly (por = 0.001) in all treatment groups, but improvements were comparable across the treatment groups.In patients with persistent asthma treated with FSC, the addition of montelukast or FPANS for the treatment of SAR resulted in no additional improvements in overall asthma control compared with FSC alone. However, FPANS provided superior rhinitis control compared with montelukast. These data suggest that asthma and rhinitis should each be optimally treated.

To examine and compare the efficacy and safety of salmeterol xinafoate, a long-acting inhaled beta2-adrenergic agonist, with inhaled ipratropium bromide and inhaled placebo in patients with COPD.A stratified, randomized, double-blind, double-dummy, placebo-controlled, parallel group clinical trial.Multiple sites at clinics and university medical centers throughout the United States.Four hundred eleven symptomatic patients with COPD with FEV1or = 65% predicted and no clinically significant concurrent disease.Comparison of inhaled salmeterol (42 microg twice daily), inhaled ipratropium bromide (36 microg four times a day), and inhaled placebo (2 puffs four times a day) over 12 weeks.Salmeterol xinafoate was significantly (p0.0001) better than placebo and ipratropium in improving lung function at the recommended doses over the 12-week trial. Both salmeterol and ipratropium reduced dyspnea related to activities of daily living compared with placebo; this improvement was associated with reduced use of supplemental albuterol. Analyses of time to first COPD exacerbation revealed salmeterol to be superior to placebo and ipratropium (p0.05). Adverse effects were similar among the three treatments.These collective data support the use of salmeterol as first-line bronchodilator therapy for the long-term treatment of airflow obstruction in patients with COPD.