A RANDOMIZED CONTROLLED TRIAL COMPARING ZILEUTON WITH THEOPHYLLINE INMODERATE ASTHMA

Background: Zileuton, a leukotriene pathway inhibitor, was compared wi th slowly absorbed theophylline in a randomized, double-blind study of patients with chronic asthma. The primary efficacy measure was improv ement in forced expiratory volume in 1 second (FEV1). Methods: Eligibi lity criteria included FEV1 of 40% to 80% of predicted, documented rev ersibility of airway disease, and age 18 to 60 years. Initially, the t heophylline dosage was titrated to achieve trough concentrations of 8 to 15 mu g/mt. After washout and 1-week placebo lead-in, patients were randomly assigned to 13 weeks of the appropriate theophylline dose or zileuton, 400 or 600 mg 4 times daily. The FEV1 was measured before t he morning dose at 2-week intervals and serially after the dose on day s 36 and 92. Patients kept daily diaries of asthma symptoms, beta-agon ist usage, and peak expiratory flow rate; on days 36 and 92, they comp leted quality-of-life questionnaires. Results: Of 471 eligible patient s at 38 centers, 377 were randomly assigned to the study; 313 complete d the study. On first-dose administration, all groups showed 11% to 13 % improvement in FEV1 within 30 minutes. Patients who received zileuto n, 400 mg, had significantly greater improvement at several points tha n did theophylline-treated patients. The range of long-term maximum im provement in FEV1 in the groups was 30% to 34% (P=.40 for zileuton 600 mg; P=.90 for zileuton 400 mg vs theophylline). Initially, the theoph ylline group improved significantly more in symptom scores, beta-agoni st usage, and peak expiratory flow rate, but at maximal effect there w as no significant difference. All groups showed significant improvemen t in quality of life. No overall differences were observed between the zileuton dosage groups. Adverse events were comparable in all groups. Conclusion: Zileuton appears as effective and safe as theophylline in patients with chronic asthma.