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Lancet. 2009 Aug 29;374(9691):695-703. doi: 10.1016/S0140-6736(09)61252-6.

Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials.

Collaborators (438)

Abdulla R, Abdullah I, Adler M, Aguilaniu, Albert I, Almonacid C, Altés A, Amaducci S, Angrill J, Antonana JM, Artner H, Bálint B, Bantje TA, Barbé F, Bateman E, Bauchnect E, Belda J, Bernabeu L, Bettendorf A, Blagden M, Blanquer R, Blecher L, Bonnaud F, Bourbeau J, Boyer GR, Brotons C, Brüning AH, Bucca C, Burns GE, von der Heydt BB, Caldwell, Canonica GW, Carter J, Chan V, Chapman KR, Chapman G, Cheung D, Chiner E, Chopra A, Clini E, Coulet P, Craig B, Croonenborghs L, Czompó M, Dal Negro RW, Dapper T, de Graaff CS, Ramos Pde L, De Munck DR, Decramer M, Delobbe A, Denier W, De-Teresa L, Dhar A, Di Maria G, Dupouy J, Duschek G, Echave J, Esteban C, Farmer IS, Flemale A, Fletcher P, Foden, Fouquert L, Franz KH, Frognier, Gagnon M, Garcia Mdel M, Garelli G, Gehling U, Ginko T, Glekin B, Gooding T, Graham A, Greillier P, Greses JV, Grillenberger J, Gross B, Grygier H, Györi Z, Harper, Henein S, Heredia JL, Hernandez P, Hoefer M, Hoffstein V, Holgate K, Höller W, Holub G, Homik L, Houle PA, Hutter C, Hyvernat P, Irusen EM, Jackson A, Janisty W, Jasnot JY, Joubert J, Juhasz G, Jullian H, Kafe H, Kelly P, Kidney J, Killian K, Kinch H, Kirsten DL, Kleinecke-Pohl U, Korlipara K, Krige LP, Kroker A, Kuipers AF, Labrecque M, Larivee P, Laskowitz C, Le Merre C, Lemoigne F, Ludwig-Sengpiel A, Luengo M, Luton R, MacNee W, Ali SM, Maltais F, Mansur A, Marciniuk D, Marín A, Martin P, Martinot JB, Mazza F, Mc Bride, McDonald B, McKinnon C, Mclvor A, McNally D, Mengeot PM, Messner J, Moder G, Mooney P, Moretti AM, Muller D, Murio C, Nardini S, Nel A, Ochoa, de Saracho JO, Paggiaro P, Paradis B, Patrick J, Peché R, Pellicer C, Perez T, Pérez E, de Llano LA, Philteos G, Pieters WR, Pigearias B, Pohl W, Popovic R, Prins M, Querfurt H, Rajkay K, Ras G, Road J, Roig J, Roldaan AC, Rolke M, Rozen D, Sanchez-Toril F, Savani N, Savary L, Schiavina M, Schiesbühl H, Schreurs AJ, Schröder-Babo W, Schürmann W, Seiz V, Sevette C, Sharma R, Shum C, Damsté HE, Smithers A, Soler JJ, Steffen H, Steinhauser U, Sweilem M, Tellier G, Terol B, Terzano C, Timar M, Toma G, Monserrat PT, Trauth HA, Valyon E, Van den Brande, van Noord JA, Vaquer JV, Hernandez-Hector HV, Vereecken G, Verkindre C, Vígh M, Viljoen JJ, Vincken W, Vinkler I, Visser S, Volgmann L, Vorderstrasse W, Voves R, Vrancken F, Weber HH, Wielders PL, Willoughby P, Würtz J, Yang W, Zabaleta M, Zachgo W, Zanini A, Zeiner M, Zeiner M, Michael H, Grillenberger J, Holub G, Popovic R, Würtz J, Duschek G, Janistyn W, Hutter C, Schiesbühl H, Messner J, Pohl W, Sweilem M, Voves R, Höller W, Moder G, Vincken W, Decramer M, Martinot JB, Croonenborghs L, Rozen D, Vereecken G, Denier W, Flemale A, Vrancken F, Delobbe A, Frognier, Peché R, Van den Brande, Delobbe A, Mengeot PM, Maltais F, Bourbeau J, Mclvor A, Larivee P, Craig B, Road J, Houle PA, Yang W, Chapman KR, Gagnon M, Luton R, Hernandez P, Homik L, Marciniuk D, Henein S, Hoffstein V, Killian K, Paradis B, Carter J, Labrecque M, Willoughby P, Abdulla R, Philteos G, Chan V, Dhar A, Tellier G, Hyvernat P, Perez T, Kafe H, Dupouy J, Coulet P, Pigearias B, Jullian H, Fouquert L, Boyer GR, Bernabeu L, Verkindre C, Bettendorf A, Jasnot JY, Aguilaniu, Savary L, Bonnaud F, Lemoigne F, Sevette C, Greillier P, Muller D, Terol B, Le Merre C, Hoefer M, Trauth HA, Querfurt H, Volgmann L, Steinhauser U, Ginko T, Franz KH, Kroker A, Schröder-Babo W, Gehling U, Martin P, Ludwig-Sengpiel A, Dapper T, Zachgo W, Kleinecke-Pohl U, Rolke M, Blecher L, Steffen H, Grygier H, Weber HH, Vorderstrasse W, Schürmann W, Laskowitz C, Seiz V, Gross B, von der Heydt BB, Valyon E, Czompó M, Juhasz G, Györi Z, Timar M, Albert I, Rajkay K, Bauchnect E, Vinkler I, Bálint B, Vígh M, Amaducci S, Canonica GW, Di Maria G, Zanini A, Paggiaro P, Schiavina M, Dal Negro RW, Mazza F, Toma G, Bucca C, Terzano C, Garelli G, Moretti AM, Nardini S, Fabbri L, Barbaro MP, Canonica GW, Clini E, Wielders PL, Kuipers AF, de Graaff CS, Cheung D, Damsté HE, Pieters WR, Schreurs AJ, van Noord JA, De Munck DR, Bantje TA, Roldaan AC, Irusen EM, Ras G, Prins M, Bateman E, Joubert J, Abdullah I, Visser S, Brüning AH, Viljoen JJ, Krige LP, Nel A, Kirsten DL, Izquierdo JL, Garcia Mdel M, Shum C, Chiner E, Heredia JL, Zabaleta M, Luengo M, de Saracho JO, Monserrat PT, Vaquer JV, Marín A, Angrill J, Brotons C, Altés A, Pérez E, Sanchez-Toril F, Ramos Pde L, Hernandez-Hector HV, Almonacid C, Belda J, Antonana JM, Blanquer R, Soler JJ, Barbé F, Murio C, De-Teresa L, Esteban C, Greses JV, Pellicer C, Echave J, de Llano LA, Roig J, Chopra A, Savani N, Glekin B, Jackson A, Blagden M, Sharma R, Chapman G, McNally D, Patrick J, Mc Bride, Burns GE, Kidney J, Kelly P, MacNee W, Kinch H, Ali SM, Adler M, Blagden M, Mooney P, Caldwell, Farmer IS, Graham A, Holgate K, Fletcher P, Korlipara K, McDonald B, McKinnon C, Smithers A, Mansur A, Gooding T, Harper, Ochoa, Foden.

Author information

1
University of Modena and Reggio Emilia, Modena, Italy.

Abstract

BACKGROUND:

Patients with chronic obstructive pulmonary disease (COPD) have few options for treatment. The efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast have been investigated in studies of patients with moderate-to-severe COPD, but not in those concomitantly treated with longacting inhaled bronchodilators. The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated.

METHODS:

In two double-blind, multicentre studies done in an outpatient setting, after a 4-week run-in, patients older than 40 years with moderate-to-severe COPD were randomly assigned to oral roflumilast 500 microg or placebo once a day for 24 weeks, in addition to salmeterol (M2-127 study) or tiotropium (M2-128 study). The primary endpoint was change in prebronchodilator forced expiratory volume in 1 s (FEV(1)). Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, number NCT00313209 for M2-127, and NCT00424268 for M2-128.

FINDINGS:

In the salmeterol plus roflumilast trial, 466 patients were assigned to and treated with roflumilast and 467 with placebo; in the tiotropium plus roflumilast trial, 371 patients were assigned to and treated with roflumilast and 372 with placebo. Compared with placebo, roflumilast consistently improved mean prebronchodilator FEV(1) by 49 mL (p<0.0001) in patients treated with salmeterol, and 80 mL (p<0.0001) in those treated with tiotropium. Similar improvement in postbronchodilator FEV(1) was noted in both groups. Furthermore, roflumilast had beneficial effects on other lung function measurements and on selected patient-reported outcomes in both groups. Nausea, diarrhoea, weight loss, and, to a lesser extent, headache were more frequent in patients in the roflumilast groups. These adverse events were associated with increased patient withdrawal.

INTERPRETATION:

Roflumilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients.

FUNDING:

Nycomed.

PMID:
19716961
DOI:
10.1016/S0140-6736(09)61252-6
[Indexed for MEDLINE]

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