A randomized controlled trial comparing zileuton with theophylline in moderate asthma. The Zileuton Study Group.
BACKGROUND
Zileuton, a leukotriene pathway inhibitor, was compared with slowly absorbed theophylline in a randomized, double-blind study of patients with chronic asthma. The primary efficacy measure was improvement in forced expiratory volume in 1 second (FEV1).


METHODS
Eligibility criteria included FEV1 of 40% to 80% of predicted, documented reversibility of airway disease, and age 18 to 60 years. Initially, the theophylline dosage was titrated to achieve trough concentrations of 8 to 15 micrograms/mL. 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 the morning dose at 2-week intervals and serially after the dose on days 36 and 92. Patients kept daily diaries of asthma symptoms, beta-agonist usage, and peak expiratory flow rate; on days 36 and 92, they completed quality-of-life questionnaires.


RESULTS
Of 471 eligible patients at 38 centers, 377 were randomly assigned to the study; 313 completed the study. On first-dose administration, all groups showed 11% to 13% improvement in FEV1 within 30 minutes. Patients who received zileuton, 400 mg, had significantly greater improvement at several points than did theophylline-treated patients. The range of long-term maximum improvement 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 theophylline group improved significantly more in symptom scores, beta-agonist usage, and peak expiratory flow rate, but at maximal effect there was no significant difference. All groups showed significant improvement in quality of life. No overall differences were observed between the zileuton dosage groups. Adverse events were comparable in all groups.


CONCLUSIONS
Zileuton appears as effective and safe as theophylline in patients with chronic asthma.
Schwartz
H J
HJ
Department of Medicine, University Hospitals of Cleveland, Ohio, USA.
Petty
T
T
Dubé
L M
LM
Swanson
L J
LJ
Lancaster
J F
JF
D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016859:Lipoxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D008176:Lung Volume Measurements; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013806:Theophylline / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D001993:Bronchodilator Agents; D016859:Lipoxygenase Inhibitors; D013806:Theophylline; C063449:zileuton; D006918:Hydroxyurea