BACKGROUND: Experimental studies have shown that doxofylline is endowedwith a remarkable bronchodilator activity with less extra-respiratory effects than theophylline. Thistrial was designed to compare the efficacy and safety of doxofylline, theophylline, and placebo in patientswith chronic reversible bronchial asthma. MATERIAL/METHODS: Three hundred forty-six patients were randomlyassigned to a 12-week oral treatment with either doxofylline 400 mg t.i.d. (high dose), doxofylline 200mg t.i.d. (low dose), theophylline 250 mg t.i.d. (active control) or placebo. Pulmonary function tests(PFTs) were performed biweekly. Patients kept records of peak flow meter (PFM) measurements, asthma attackrate and beta-2-agonist use (albuterol). RESULTS: Changes in FEV1 2 hours after the administration oftreatments versus baseline exhibited statistically significant differences between doxofylline 400 mgt.i.d. and placebo and between theophylline and placebo. Similar differences were monitored on the othervariables (FVC, PFER, FEF(25-75%). Asthma attack rate and use of albuterol decreased remarkably withdoxofylline 400 mg t.i.d. and theophylline. There were few statistically significant differences betweendoxofylline 200 mg t.i.d. and placebo. Significantly more patients had to interrupt treatment becauseof adverse events under theophylline than under doxofylline 400 mg t.i.d. (p=0.001). With doxofylline400 mg t.i.d., the number of patients treated to spare one drop-out due to theophylline was 5. CONCLUSIONS:This study provides evidence that doxofylline 400 mg t.i.d. is an effective treatment for relieving airwayobstruction and displays a better safety profile with respect to theophylline 250 mg t.i.d. with a favorablerisk-to-benefit ratio.

Keywords: Adrenergic beta-Agonists, Albuterol, Anti-Asthmatic Agents, Asthma, Comparative Study, Dose-Response Relationship, Drug, Double-Blind Method, Drug Therapy, Combination, Forced Expiratory Volume, Gastrointestinal Diseases, Headache, Placebos, Respiratory Function Tests, Safety, Single-Blind Method, Tachycardia, Theophylline