Effects of roflumilast in COPD patients receiving inhaled corticosteroid/long-acting &beta;<sub>2</sub>-agonist fixed-dose combination: RE<sup>2</sup>SPOND rationale and study design Journal Articles uri icon

  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All


  • BACKGROUND: Roflumilast, a once-daily, selective phosphodiesterase-4 inhibitor, reduces the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. The RE(2)SPOND study is examining whether roflumilast, when added to an inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) fixed-dose combination (FDC), further reduces exacerbations. The methodology is described herein. METHODS: In this Phase IV, multicenter, double-blind, placebo-controlled, parallel-group trial, participants were randomized 1:1 (stratified by long-acting muscarinic antagonist use) to receive roflumilast or placebo, plus ICS/LABA FDC, for 52 weeks. Eligible participants had severe COPD associated with chronic bronchitis, had two or more moderate-severe exacerbations within 12 months, and were receiving ICS/LABA FDC for ≥3 months. The primary efficacy measure is the rate of moderate or severe COPD exacerbations per participant per year. The secondary efficacy outcomes include mean change in prebronchodilator forced expiratory volume in 1 second (FEV1) over 52 weeks, rate of severe exacerbations, and rate of moderate, severe, or antibiotic-treated exacerbations. Additional assessments include spirometry, rescue medication use, the COPD assessment test, daily symptoms using the EXACT-Respiratory symptoms (E-RS) questionnaire, all-cause and COPD-related hospitalizations, and safety and pharmacokinetic measures. RESULTS: Across 17 countries, 2,354 participants were randomized from September 2011 to October 2014. Enrollment goal was met in October 2014, and study completion occurred in June 2016. CONCLUSION: This study will further characterize the effects of roflumilast added to ICS/LABA on exacerbation rates, lung function, and health of severe-very severe COPD participants at risk of further exacerbations. The results will determine the clinical benefits of roflumilast combined with standard-of-care inhaled COPD treatment.


  • Rennard, Stephen
  • Martinez, Fernando
  • Rabe, Klaus
  • Sethi, Sanjay
  • Pizzichini, Emilio
  • McIvor, Andrew
  • Siddiqui, Shahid
  • Anzueto, Antonio
  • Zhu, Haiyuan

publication date

  • 2016

has subject area