Effect of Roflumilast and Inhaled Corticosteroid/Long-Acting β2-Agonist on Chronic Obstructive Pulmonary Disease Exacerbations (RE2SPOND). A Randomized Clinical Trial

• DOI: 10.1164/rccm.201607-1349oc
• Publication Date: 2016-09-01T15:18:33Z
• Authors: Fernando J. Martinez; Klaus F. Rabe; Sanjay Sethi; Emilio Pizzichini; Andrew McIvor; Antonio Anzueto; Vijay K. T. Alaga...; Shahid Siddiqui; Ludmyla Rekeda; Christopher J. Mi...; Sofia Zetterstrand; Colin Reisner; Stephen I. Rennard
• Keywords: Roflumilast; Muscarinic antagonist; Clinical endpoint; Chronic bronchitis

Rationale: Moderate and severe exacerbations are incompletely prevented by maximal inhalation therapy in patients with chronic obstructive pulmonary disease.Objectives: To determine whether roflumilast reduces moderate and/or disease at risk for despite treatment inhaled corticosteroid/long-acting β2-agonist or without a long-acting muscarinic antagonist (LAMA).Methods: In this 52-week, phase 4, double-blind, placebo-controlled RE2SPOND (Roflumilast Effect on Exacerbations Patients Dual [LABA/ICS] Therapy) trial (NCT01443845), participants aged 40 years older severe/very disease, bronchitis, two more hospitalizations the previous year, receiving LAMA daily 3 months were equally randomized to once-daily roflumilast, 500 μg (n = 1,178), placebo 1,176). Stratification was based use.Measurements Main Results: Although rate of per patient year (primary endpoint) reduced 8.5% versus placebo, between-group difference not statistically significant (rate ratio, 0.92; 95% confidence interval, 0.81–1.04; P 0.163). However, improved lung function, post hoc analysis significantly history than three one prior year. Adverse event–related discontinuations occurred 11.7% roflumilast-treated 5.4% placebo-treated participants. Deaths 2.5% 2.1% participants.Conclusions: Roflumilast failed reduce overall population. function frequent hospitalization history. The safety profile consistent that studies.Clinical registered www.clinicaltrials.gov (NCT01443845).