Does roflumilast decrease exacerbations in severe COPD patients not controlled by inhaled combination therapy? The REACT study protocol.
Peter M.A. Calverley,Fernando J. Martinez,Leonardo M. Fabbri,Udo-Michael Goehring,Klaus F. Rabe +4 more
TL;DR: 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.
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Abstract: 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
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Citations
Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicentre randomised controlled trial
Fernando J. Martinez,Fernando J. Martinez,Peter M.A. Calverley,Udo-Michael Goehring,Manja Brose,Leonardo M. Fabbri,Klaus F. Rabe +6 more
TL;DR: It is suggested that roflumilast reduces exacerbations and hospital admissions in patients with severe chronic obstructive pulmonary disease and chronic bronchitis who are at risk of frequent and severe exacerbations despite inhaled corticosteroid and longacting β2 agonist therapy, even in combination with tiotropium.
367
Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease
TL;DR: Roflumilast and cilomilast are oral phosphodiesterase 4 (PDE4) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD and were associated with weight loss during the trial period and an increase in insomnia and depressive mood symptoms.
257
Roflumilast: a review of its use in the treatment of COPD.
TL;DR: Roflumilast as mentioned in this paper is a potent and selective inhibitor of the enzyme phosphodiesterase-4 that targets the systemic inflammation associated with COPD, which is associated with worsening airflow limitation over time and increased frequency of COPD exacerbations.
Phosphodiesterase-4 inhibitor therapy for lung diseases.
TL;DR: Roflumilast, the only PDE4 inhibitor that has reached the market because of the good efficacy/tolerability ratio, is recommended for patients with COPD with severe airflow limitation, symptoms of chronic bronchitis, and a history of exacerbations, whose disease is not adequately controlled by long-acting bronchodilators.
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Roflumilast: the new orally active, selective phophodiesterase-4 inhibitor, for the treatment of COPD
TL;DR: Roflumilast is the first drug specifically targeted to a particular subset of the heterogeneous population of COPD patients, namely those with chronic bronchitis in addition to severe airflow obstruction and an exacerbation history, and underscores its potential utility as an add-on agent in patients who continue to experience exacerbations despite treatment with other agents.
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References
Ascertainment of Cause-Specific Mortality in COPD -- Operations of the TORCH Clinical Endpoint Committee
TL;DR: A CEC can provide standardised, reliable and informative adjudication of COPD mortality that provides information which frequently differs from data collected from assessment by site investigators.
562
Increased Risk of Myocardial Infarction and Stroke Following Exacerbation of COPD
TL;DR: Exacerbations of COPD increase the risk of MI and stroke, and this may have implications for therapy in both stable and exacerbated COPD.
520
Roflumilast--an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial.
Klaus F. Rabe,Eric D. Bateman,Denis E. O'Donnell,Stephan Witte,Dirk Bredenbröker,T.D. Bethke +5 more
TL;DR: Roflumilast is a promising candidate for anti-inflammatory COPD treatment because it improved lung function and reduced exacerbations compared with placebo and long-term studies are needed to fully assess the effect on health-related quality of life.
479
Inflammatory changes, recovery and recurrence at COPD exacerbation
W. R. Perera,John R. Hurst,Tom Wilkinson,Raymond J. Sapsford,Hana Müllerová,Gavin C. Donaldson,Jadwiga A. Wedzicha +6 more
TL;DR: Nonrecovery of symptoms at chronic obstructive pulmonary disease exacerbation is associated with persistently heightened systemic inflammation, and a high serum C-reactive protein concentration 14 days after an index exacerbation may be used as a predictor of recurrent exacerbations within 50 days.
387
Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease.
Peter M.A. Calverley,Fernando Sanchez-Toril,Andrew McIvor,Peter Teichmann,Dirk Bredenbroeker,Leonardo M. Fabbri +5 more
TL;DR: In severe, stable COPD, PDE4 inhibition with roflumilast produced a modest but significant improvement in lung function without changing the exacerbation rate or health status.
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