Leukotrienes mediate asthma and cause bronchoconstriction, mucus secretion and increased vascular permeability. Knorr and colleagues conducted a randomized double-blind, placebo-controlled study of the safety and efficacy of montelukast, a leukotriene receptor antagonist, in six- to 14-year-old children with asthma.
Patients were eligible to participate in the study if their forced expiratory volume in one second (FEV1) was between 50 and 85 percent of predicted values and if the FEV1 increased by 15 percent after administration of an inhaled beta agonist. A minimum number of daytime asthma symptoms were also required for entry into the study. Patients were excluded if they had acute respiratory infections within the preceding three weeks or required recent emergency treatment of asthma.
The eight-week multicenter study included 336 children; 201 received montelukast, and 135 received placebo. After a two-week run-in period, children were randomized to receive either placebo or 5 mg of montelukast at bedtime. Short-acting inhaled beta agonists and inhaled steroids were also allowed for the treatment of asthma. FEV1 and peak expiratory flow rate were measured at each clinic visit, and patients measured their own peak flow rate each morning and at bedtime. Global evaluations of the patient's condition were completed by the patient, the parents and the physician.
FEV1 was significantly improved in patients receiving montelukast compared with patients receiving placebo. The amount of daily beta agonist needed and the proportion of days that patients experienced asthma exacerbations decreased in the montelukast group compared with the placebo group. Physicians' global assessments of improvement did not meet a statistically significant different in the two groups, although the authors note that the study was not designed to detect such a difference.
The onset of action of montelukast was less than one day after the first dose. No major differences in the occurrence of adverse effects existed between the montelukast and the placebo groups except for allergic rhinitis, which was significantly more frequent in the placebo group.
The authors conclude that montelukast is both safe and effective in children aged six to 14 years who have mild to moderately severe asthma.