Effect of roflumilast and inhaledcorticosteroid/long-acting b2-agonist on chronic obstructive pulmonary disease exacerbations (RE2SPOND): A randomized clinical trial

American Journal of Respiratory and Critical Care Medicine

Volumn 194, Issue 5, 2016, Pages 559-567

  Martinez, Fernando J ^a   Rabe, Klaus F ^b,c,d   Sethi, Sanjay ^e   Pizzichini, Emilio ^f   McIvor, Andrew ^g   Anzueto, Antonio ^h,i   Alagappan, Vijay K T ^j   Siddiqui, Shahid ^j   Rekeda, Ludmyla ^k   Miller, Christopher J ^j   Zetterstrand, Sofia ^l   Reisner, Colin ^j   Rennard, Stephen I ^j,m  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

^b Zytologisches Labor   (Germany)

^c Kiel and Lungen Clinic Grosshansdorf   (Germany)

^d Member of the German Center for Lung Research   (Germany)

^e UNIVERSITY AT BUFFALO   (United States)

^f FEDERAL UNIVERSITY OF SANTA CATARINA   (Brazil)

^g MCMASTER UNIVERSITY   (Canada)

^h UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

ⁱ SOUTH TEXAS VETERANS HEALTH CARE SYSTEM   (United States)

^j ASTRAZENECA   (United Kingdom)

^k ALLERGAN PLC   (United States)

^l ASTRAZENECA R AND D   (Sweden)

^m UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

more..

Author keywords

Bronchodilators; Clinical trial; Hospitalization; Phosphodiesterase 4 inhibitor

Indexed keywords

BUDESONIDE PLUS FORMOTEROL; FLUTICASONE PROPIONATE PLUS SALMETEROL; PLACEBO; ROFLUMILAST; AMINOPYRIDINE DERIVATIVE; BENZAMIDE DERIVATIVE; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; BRONCHODILATING AGENT; CORTICOSTEROID; CYCLOPROPANE DERIVATIVE; MUSCARINIC RECEPTOR BLOCKING AGENT;

ADULT; APPETITE DISORDER; ARTICLE; BACKACHE; BODY WEIGHT DISORDER; CHRONIC BRONCHITIS; CHRONIC OBSTRUCTIVE LUNG DISEASE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CORTICOSTEROID THERAPY; DEATH; DIARRHEA; DISEASE EXACERBATION; DOUBLE BLIND PROCEDURE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG SAFETY; FEMALE; FORCED EXPIRATORY VOLUME; HEADACHE; HOSPITALIZATION; HUMAN; HYPERTENSION; INFLUENZA; INSOMNIA; LUNG FUNCTION; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; MULTICENTER STUDY; NAUSEA; PHASE 4 CLINICAL TRIAL; PRIORITY JOURNAL; RHINOPHARYNGITIS; SIDE EFFECT; SUICIDAL BEHAVIOR; SUICIDAL IDEATION; SUICIDE; SUICIDE ATTEMPT; TREATMENT OUTCOME; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; BRONCHITIS, CHRONIC; CLINICAL TRIAL; COMBINATION DRUG THERAPY; COMPLICATION; DISEASE COURSE; PROCEDURES; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; RANDOMIZED CONTROLLED TRIAL; RESPIRATORY CARE; SEVERITY OF ILLNESS INDEX;

ADRENAL CORTEX HORMONES; ADRENERGIC BETA-2 RECEPTOR AGONISTS; AMINOPYRIDINES; BENZAMIDES; BRONCHITIS, CHRONIC; BRONCHODILATOR AGENTS; CYCLOPROPANES; DISEASE PROGRESSION; DRUG THERAPY, COMBINATION; FEMALE; HUMANS; MALE; MIDDLE AGED; MUSCARINIC ANTAGONISTS; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; RESPIRATORY THERAPY; SEVERITY OF ILLNESS INDEX;

EID: 84988882477     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201607-1349OC     Document Type: Article

References (21)

1. Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2013;187:347-365.
2. Global Initiative for Chronic Obstructive Lung Disease (GOLD); 2016 [accessed 2016 June 27]. Available from: http://goldcopd.org/.
3. Müllerova H, Maselli DJ, Locantore N, Vestbo J, Hurst JR, Wedzicha JA, Bakke P, Agusti A, Anzueto A; ECLIPSE Investigators. Hospitalized exacerbations of COPD: risk factors and outcomes in the ECLIPSE cohort. Chest 2015;147:999-1007.
4. Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:1418-1422.
5. Soler-Cataluña JJ, Martínez-García MA, Román Sánchez P, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax 2005;60: 925-931.
6. Calverley PM, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ; M2-124 and M2-125 study groups. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet 2009;374:685-694.
7. Grootendorst DC, Gauw SA, Verhoosel RM, Sterk PJ, Hospers JJ, Bredenbröker D, Bethke TD, Hiemstra PS, Rabe KF. Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD. Thorax 2007;62:1081-1087.
8. Hatzelmann A, Morcillo EJ, Lungarella G, Adnot S, Sanjar S, Beume R, Schudt C, Tenor H. The preclinical pharmacology of roflumilast: a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease. Pulm Pharmacol Ther 2010; 23:235-256.
9. Tashkin DP. Roflumilast: the new orally active, selective phophodiesterase-4 inhibitor, for the treatment of COPD. Expert Opin Pharmacother 2014;15:85-96.
10. Martinez FJ, Calverley PMA, Goehring U-M, Brose M, Fabbri LM, Rabe KF. Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicentre randomised controlled trial. Lancet 2015;385:857-866.
11. Rennard SI, Martinez FJ, Rabe KF, Sethi S, Pizzichini E, McIvor A, Siddiqui S, Anzueto A, Zhu H. Effects of roflumilast in COPD patients receiving inhaled corticosteroid/long-acting b2-agonist fixed-dose combination: RE2SPOND rationale and study design. Int J Chron Obstruct Pulmon Dis 2016;11:1921-1928.
12. Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline Leidy N. Development and first validation of the COPD Assessment Test. Eur Respir J 2009;34:648-654.
13. Leidy NK, Wilcox TK, Jones PW, Murray L, Winnette R, Howard K, Petrillo J, Powers J, Sethi S; EXACT-PRO Study Group. Development of the EXAcerbations of Chronic Obstructive Pulmonary Disease Tool (EXACT): a patient-reported outcome (PRO) measure. Value Health 2010;13:965-975.
14. Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, et al. The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry 2011;168:1266-1277.
15. Miettinen O, Nurminen M. Comparative analysis of two rates. Stat Med 1985;4:213-226.
16. Wei L, Lin D, Weissfeld L. Regression analysis of multivariate incomplete failure time data by modeling marginal distributions. J Am Stat Assoc 1989;84:1065-1073.
17. Yee K. Poisson regression sample size estimation in clinical trials. ASA Biopharmaceutical Section 1998:114-118.
18. Fabbri LM, Calverley PM, Izquierdo-Alonso JL, Bundschuh DS, Brose M, Martinez FJ, Rabe KF; M2-127 and M2-128 study groups. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. Lancet 2009;374:695-703.
19. Martinez F, Calverley P, Goehring U-M, Hodge R, Fabbri L, Rabe K. Effect of roflumilast on exacerbations in patients with severe COPD and a prior history of hospitalization taking combination therapy. Eur Respir J 2015;46:OA482.
20. Wedzicha JA, Rabe KF, Martinez FJ, Bredenbröker D, Brose M, Goehring UM, Calverley PM. Efficacy of roflumilast in the COPD frequent exacerbator phenotype. Chest 2013;143: 1302-1311.
21. Woodruff PG, Agusti A, Roche N, Singh D, Martinez FJ. Current concepts in targeting chronic obstructive pulmonary disease pharmacotherapy: making progress towards personalised management. Lancet 2015;385:1789-1798.