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A Multicenter, Randomized, Double-blind Trial

Theodore F. Reiss, MD; Paul Chervinsky, MD; Robert J. Dockhorn, MD; Sumiko Shingo, MS; Beth Seidenberg, MD; Thomas B. Edwards, MD; for the Montelukast Clinical Research Study Group

Arch Intern Med. 1998;158:1213-1220.

Objectives  To determine the clinical effect of oral montelukast sodium, a leukotriene receptor antagonist, in asthmatic patients aged 15 years or more.

Design  Randomized, multicenter, double-blind, placebo-controlled, parallel-group study. A 2-week, single-blind, placebo run-in period was followed by a 12-week, double-blind treatment period (montelukast sodium, 10 mg, or matching placebo, once daily at bedtime) and a 3-week, double-blind, washout period.

Setting/Patients  Fifty clinical centers randomly allocated 681 patients with chronic, stable asthma to receive placebo or montelukast after demonstrating a forced expiratory volume in 1 second 50% to 85% of the predicted value, at least a 15% improvement in forced expiratory volume in 1 second (absolute value) after inhaled -agonist administration, a minimal predefined level of daytime asthma symptoms, and inhaled -agonist use. Twenty-three percent of the patients used concomitant inhaled corticosteroids.

Primary End Points  Forced expiratory volume in 1 second and daytime asthma symptoms.

Results  Montelukast improved airway obstruction (forced expiratory volume in 1 second, morning and evening peak expiratory flow rate) and patient-reported end points (daytime asthma symptoms, "as-needed" -agonist use, nocturnal awakenings) (P<.001 compared with placebo). Montelukast provided near-maximal effect in these end points within the first day of treatment. Tolerance and rebound worsening of asthma did not occur. Montelukast improved outcome end points, including asthma exacerbations, asthma control days (P<.001 compared with placebo), and decreased peripheral blood eosinophil counts (P<.001 compared with placebo). The incidence of adverse events and discontinuations from therapy were similar in the montelukast and placebo groups.

Conclusions  Montelukast, compared with placebo, significantly improved asthma control during a 12-week treatment period. Montelukast was generally well tolerated, with an adverse event profile comparable with that of placebo.

From the Departments of Pulmonary/Immunology (Drs Reiss and Seidenberg) and Biostatistics (Ms Shingo), Merck Research Laboratories, Rahway, NJ; NE Research Center, Inc, North Dartmouth, Mass (Dr Chervinsky); International Medical Technology Consultants Inc, Prairie Village, Kan (Dr Dockhorn); and Allergy and Asthma Center, Albany Medical Center, Albany, NY (Dr Edwards).

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