Does roflumilast decrease exacerbations in severe COPD patients not controlled by inhaled combination therapy? the REACT study protocol
Peter MA Calverley,1 Fernando J Martinez,2 Leonardo M Fabbri,3 Udo-Michael Goehring,4 Klaus F Rabe5–7
1Clinical Science Center, University Hospital Aintree, Liverpool, United Kingdom; 2Department of Internal Medicine, University of Michigan, MI, USA; 3Department of Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy; 4Nycomed (a Takeda company), Konstanz, Germany; 5University of Kiel, Kiel, Germany; 6Krankenhaus Grosshansdorf, Center for Pulmonology and Thoracic Surgery, Grosshansdorf, Germany; 7Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands
Background: Many patients with chronic obstructive pulmonary disease (COPD) continue to suffer exacerbations, even when treated with maximum recommended therapy (eg, inhaled combinations of long-acting β2-agonist and high dose inhaled corticosteroids, with or without a long-acting anticholinergic [long-acting muscarinic antagonist]). Roflumilast is approved to treat severe COPD in patients with chronic bronchitis – and a history of frequent exacerbations – as an add-on to bronchodilators.
Purpose: The REACT (Roflumilast in the Prevention of COPD Exacerbations While Taking Appropriate Combination Treatment) study (identification number RO-2455-404-RD, clinicaltrials.gov identifier NCT01329029) will investigate whether roflumilast further reduces exacerbations when added to inhaled combination therapy in patients still suffering from frequent exacerbations.
Patients and methods: REACT is a 1-year randomized, double-blind, multicenter, phase III/IV study of roflumilast 500 µg once daily or placebo on top of a fixed long-acting β2-agonist/inhaled corticosteroid combination. A concomitant long-acting muscarinic antagonist will be allowed at stable doses. The primary outcome is the rate of moderate or severe COPD exacerbations. Using a Poisson regression model with a two-sided significance level of 5%, a sample size of 967 patients per treatment group is needed for 90% power. COPD patients with severe to very severe airflow limitation, symptoms of chronic bronchitis, and at least two exacerbations in the previous year will be recruited.
Conclusion: It is hypothesized that because roflumilast
(a phosphodiesterase-4 inhibitor) has a different mode of action to bronchodilators and inhaled corticosteroids, it may provide additional benefits when added to these treatments in frequent exacerbators. REACT will be important to determine the role of roflumilast in COPD management. Here, the design and rationale for this important study is described.
Keywords: chronic obstructive pulmonary disease, roflumilast, protocol, LABA, ICS, exacerbation
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