Effects of Roflumilast on Rehospitalization and Mortality in Patients

Introduction: Hospitalization for chronic obstructive pulmonary disease (COPD) exacerbation portends the greatest risk of rehospitalization and mortality. Treatments that prevent hospitalizations could significantly lessen COPD morbidity and mortality. Methods: We performed a prospective, randomized, double-blind, placebo-controlled study of roflumilast 500 ug daily versus placebo in patients hospitalized for acute COPD exacerbation. Primary outcome was time to all-cause mortality or non-elective rehospitalization at 180 days post-randomization. Secondary outcomes were death or hospitalization from a respiratory cause, quality of life, change in health status, forced expiratory volume in 1 second (FEV₁) and roflumilast tolerance. Results: A total of 64 patients with moderate to severe COPD (FEV₁, 37.6 ± 16.4% predicted; 61% female, 61.6 ± 7.9 years old) were assigned to roflumilast or placebo. No deaths occurred in the follow-up period. There was no difference in the time to first readmission between the roflumilast and placebo groups (46.1 days versus 47.3 days respectively, p=0.93). There were 29 and 30 readmissions in the roflumilast and placebo groups, respectively (p=0.47). The St George's Respiratory Questionnaire (SGRQ) decreased 10.8 points and 7.8 points in the roflumilast and placebo groups, respectively and were not different. EuroQuality of Life Five Dimension scale (EQ5D) scores improved, but not significantly in either group. Weight loss and nausea were more common with roflumilast but not different from placebo. Change in glycosylated hemoglobin percentage (HgbA1C%) was not different between groups. Sub-analysis for the impact of chronic bronchitis did not affect outcomes. Conclusion: In this pilot study conducted in patients hospitalized with an exacerbation of COPD, roflumilast did not affect time to all-cause rehospitalization, quality of life, FEV₁ or any other measured parameter.