Purpose of the Study
To determine the clinical effect of oral montelukast sodium, a leukotriene receptor antagonist, in asthmatic patients aged 15 years or more.
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 (FEV1) 50% to 85% of the predicted value, at least a 15% improvement FEV1(absolute value) after inhaled β-agonist administration, a minimal predefined level of daytime asthma symptoms, and inhaled β-agonist use. Twenty-three percent of the patients used concomitant inhaled corticosteroids.
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. FEV1 and daytime asthma symptoms were the primary endpoint measures.
Montelukast improved airway obstruction (FEV1, morning and evening peak expiratory flow rate) and patient-reported endpoints (daytime asthma symptoms, “as-needed” β-agonist use, nocturnal awakenings) (P < .001 compared with placebo). Montelukast provided near-maximal effect in these endpoints within the first day of treatment. Tolerance and rebound worsening of asthma did not occur. Montelukast improved outcome endpoints, 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.
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.
This study appears to be a variation on a theme of previous studies with similar results. Montelukast (Singulair) and zafirlukast (Accolate) seem to be very useful medications for at least mild persistent asthma, particularly in patients who have grown weary of inhaled preparations. Montelukast has advantages over zafirlukast of once daily dosing without regard to food intake, and a pediatric approved chewable preparation. Montelukast has been shown helpful in exercise-induced bronchospasm (Kemp, J Allergy Clin Immunol. 1997;99:S321), aspirin-intolerant asthma (Kuna,Am J Respir Crit Care Med. 1997;155:A975), and in reducing the dose of inhaled corticosteroids (Leff, Am J Respir Crit Care Med. 1997;155:A976). Recent concerns regarding Churg-Strauss vasculitis may dampen some of the enthusiasm.