Comparison of the efficacy and tolerability of mepifylline oral solution versus inhaled ipratropium bromide in patients with stable chronic obstructive pulmonary disease: A randomized, active-controlled, open-label study

Abstract

Background: Inhaled ipratropium bromide, through a metered-dose inhaler (MDI), is a first-line treatment for the prevention of exacerbations of chronic obstructive pulmonary disease (COPD). However, MDIs are often used incorrectly by patients, and the efficacy of inhaled medications may be affected as a result. Objective: The purpose of this study was to compare the efficacy and tolerability of inhaled ipratropium bromide versus oral mepifylline in the prevention of medical events among patients with COPD. Methods: This was an open-label, randomized, parallel-group, active-controlled study. Patients with stable COPD were randomly assigned to receive 75 mg mepifylline by the oral route every 8 hours or 0.04 mg ipratropium bromide inhaled every 6 hours, for 6 months. A medical event was defined as any unanticipated, COPD-related event requiring extra medical care. Secondary end points were pulmonary function, intensity of dyspnea on the Borg scale, distance on the 6-minute walking test (and intensity and subjective feelings of dyspnea before and/or after the test), blood gas and inspiratory pressures, and use of any type of medication to control COPD symptoms. Results: A total of 134 patients were enrolled. After 6 months of treatment, oral mepifylline and inhaled ipratropium bromide were equally effective in preventing medical events. Forced expiratory volume in 1 second (FEV 1) and forced vital capacity (FVC) decreased slightly but significantly versus baseline ( P = 0.018). In both groups, a decrease in dyspnea ( P = 0.054) and an increase in the distance covered in the walking test were observed. The subjective feeling of dyspnea after the 6-minute walking test decreased significantly among the patients treated with mepifylline ( P = 0.01 vs baseline), but not among those treated with ipratropium bromide ( P = 0.172 vs baseline). The need for rescue medication decreased throughout the study, with no differences between treatment groups. A significantly greater number of gastrointestinal adverse events were seen in the mepifylline group ( P = 0.003). Conclusion: Mepifylline is as effective as ipratropium bromide in controlling symptoms and preventing medical events in patients with COPD, and can be considered a good therapeutic alternative to inhaled ipratropium bromide.