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Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials

Summary Background The phosphodiesterase-4 inhibitor roflumilast can improve lung function and prevent exacerbations in certain patients with chronic obstructive pulmonary disease (COPD). We therefore investigated whether roflumilast would reduce the frequency of exacerbations requiring corticostero... Full description

Journal Title: The Lancet (British edition) 2009, Vol.374 (9691), p.685-694
Main Author: Calverley, Peter MA, Prof
Other Authors: Rabe, Klaus F, Prof , Goehring, Udo-Michael, MD , Kristiansen, Søren, PhD , Fabbri, Leonardo M, Prof , Martinez, Fernando J, Prof
Format: Electronic Article Electronic Article
Language: English
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Quelle: Alma/SFX Local Collection
Publisher: Kidlington: Elsevier Ltd
ID: ISSN: 0140-6736
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title: Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials
format: Article
creator:
  • Calverley, Peter MA, Prof
  • Rabe, Klaus F, Prof
  • Goehring, Udo-Michael, MD
  • Kristiansen, Søren, PhD
  • Fabbri, Leonardo M, Prof
  • Martinez, Fernando J, Prof
subjects:
  • Abridged Index Medicus
  • Administration, Oral
  • Adrenergic beta-Agonists - therapeutic use
  • Aged
  • air flow
  • Aminopyridines - pharmacology
  • Aminopyridines - therapeutic use
  • Analysis of Variance
  • Benzamides - pharmacology
  • Benzamides - therapeutic use
  • Biological and medical sciences
  • Cholinergic Antagonists - therapeutic use
  • Chronic obstructive pulmonary disease
  • Clinical trials
  • Corticoids
  • Cyclopropanes - pharmacology
  • Cyclopropanes - therapeutic use
  • Disease management
  • Dosage and administration
  • Double-Blind Method
  • Drug therapy
  • Drug Therapy, Combination
  • Enzyme inhibitors
  • Female
  • Forced Expiratory Volume - drug effects
  • General aspects
  • Health economics
  • Historical account
  • Humans
  • Internal Medicine
  • Lung diseases, Obstructive
  • Male
  • Medical sciences
  • Middle Aged
  • Motivation
  • Phosphodiesterase 4 Inhibitors
  • Phosphodiesterase Inhibitors - pharmacology
  • Phosphodiesterase Inhibitors - therapeutic use
  • Proportional Hazards Models
  • Pulmonary Disease, Chronic Obstructive - diagnosis
  • Pulmonary Disease, Chronic Obstructive - drug therapy
  • Pulmonary Disease, Chronic Obstructive - etiology
  • Regression Analysis
  • Respiratory function
  • Severity of Illness Index
  • Side effects
  • Smoking
  • Smoking - epidemiology
  • Studies
  • Treatment Outcome
  • Vital Capacity - drug effects
ispartof: The Lancet (British edition), 2009, Vol.374 (9691), p.685-694
description: Summary Background The phosphodiesterase-4 inhibitor roflumilast can improve lung function and prevent exacerbations in certain patients with chronic obstructive pulmonary disease (COPD). We therefore investigated whether roflumilast would reduce the frequency of exacerbations requiring corticosteroids in patients with COPD. Methods In two placebo-controlled, double-blind, multicentre trials (M2-124 and M2-125) with identical design that were done in two different populations in an outpatient setting, patients with COPD older than 40 years, with severe airflow limitation, bronchitic symptoms, and a history of exacerbations were randomly assigned to oral roflumilast (500 μg once per day) or placebo for 52 weeks. Primary endpoints were change in prebronchodilator forced expiratory volume in 1 s (FEV1 ) and the rate of exacerbations that were moderate (glucocorticosteroid-treated) or severe. Analysis was by intention to treat. The trials are registered with ClinicalTrials.gov , number NCT00297102 for M2-124, and NCT00297115 for M2-125. Findings Patients were assigned to treatment, stratified according to smoking status and treatment with longacting β2 agonists, and given roflumilast (n=1537) or placebo (n=1554). In both studies, the prespecified primary endpoints were achieved and were similar in magnitude. In a pooled analysis, prebronchodilator FEV1 increased by 48 mL with roflumilast compared with placebo (p
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0140-6736
fulltext: fulltext
issn:
  • 0140-6736
  • 1474-547X
url: Link


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titleRoflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials
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creatorCalverley, Peter MA, Prof ; Rabe, Klaus F, Prof ; Goehring, Udo-Michael, MD ; Kristiansen, Søren, PhD ; Fabbri, Leonardo M, Prof ; Martinez, Fernando J, Prof
creatorcontribCalverley, Peter MA, Prof ; Rabe, Klaus F, Prof ; Goehring, Udo-Michael, MD ; Kristiansen, Søren, PhD ; Fabbri, Leonardo M, Prof ; Martinez, Fernando J, Prof ; for the M2-124 and M2-125 study groups ; M2-124 and M2-125 study groups
descriptionSummary Background The phosphodiesterase-4 inhibitor roflumilast can improve lung function and prevent exacerbations in certain patients with chronic obstructive pulmonary disease (COPD). We therefore investigated whether roflumilast would reduce the frequency of exacerbations requiring corticosteroids in patients with COPD. Methods In two placebo-controlled, double-blind, multicentre trials (M2-124 and M2-125) with identical design that were done in two different populations in an outpatient setting, patients with COPD older than 40 years, with severe airflow limitation, bronchitic symptoms, and a history of exacerbations were randomly assigned to oral roflumilast (500 μg once per day) or placebo for 52 weeks. Primary endpoints were change in prebronchodilator forced expiratory volume in 1 s (FEV1 ) and the rate of exacerbations that were moderate (glucocorticosteroid-treated) or severe. Analysis was by intention to treat. The trials are registered with ClinicalTrials.gov , number NCT00297102 for M2-124, and NCT00297115 for M2-125. Findings Patients were assigned to treatment, stratified according to smoking status and treatment with longacting β2 agonists, and given roflumilast (n=1537) or placebo (n=1554). In both studies, the prespecified primary endpoints were achieved and were similar in magnitude. In a pooled analysis, prebronchodilator FEV1 increased by 48 mL with roflumilast compared with placebo (p<0·0001). The rate of exacerbations that were moderate or severe per patient per year was 1·14 with roflumilast and 1·37 with placebo (reduction 17% [95% CI 8–25], p<0·0003). Adverse events were more common with roflumilast (1040 [67%]) than with placebo (963 [62%]); 219 (14%) patients in the roflumilast group and 177 (12%) in the placebo group discontinued because of adverse events. In the pooled analysis, the difference in weight change during the study between the roflumilast and placebo groups was −2·17 kg. Interpretation Since different subsets of patients exist within the broad spectrum of COPD, targeted specific therapies could improve disease management. This possibility should be explored further in prospective studies. Funding Nycomed.
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publisherKidlington: Elsevier Ltd
subjectAbridged Index Medicus ; Administration, Oral ; Adrenergic beta-Agonists - therapeutic use ; Aged ; air flow ; Aminopyridines - pharmacology ; Aminopyridines - therapeutic use ; Analysis of Variance ; Benzamides - pharmacology ; Benzamides - therapeutic use ; Biological and medical sciences ; Cholinergic Antagonists - therapeutic use ; Chronic obstructive pulmonary disease ; Clinical trials ; Corticoids ; Cyclopropanes - pharmacology ; Cyclopropanes - therapeutic use ; Disease management ; Dosage and administration ; Double-Blind Method ; Drug therapy ; Drug Therapy, Combination ; Enzyme inhibitors ; Female ; Forced Expiratory Volume - drug effects ; General aspects ; Health economics ; Historical account ; Humans ; Internal Medicine ; Lung diseases, Obstructive ; Male ; Medical sciences ; Middle Aged ; Motivation ; Phosphodiesterase 4 Inhibitors ; Phosphodiesterase Inhibitors - pharmacology ; Phosphodiesterase Inhibitors - therapeutic use ; Proportional Hazards Models ; Pulmonary Disease, Chronic Obstructive - diagnosis ; Pulmonary Disease, Chronic Obstructive - drug therapy ; Pulmonary Disease, Chronic Obstructive - etiology ; Regression Analysis ; Respiratory function ; Severity of Illness Index ; Side effects ; Smoking ; Smoking - epidemiology ; Studies ; Treatment Outcome ; Vital Capacity - drug effects
ispartofThe Lancet (British edition), 2009, Vol.374 (9691), p.685-694
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5Martinez, Fernando J, Prof
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descriptionSummary Background The phosphodiesterase-4 inhibitor roflumilast can improve lung function and prevent exacerbations in certain patients with chronic obstructive pulmonary disease (COPD). We therefore investigated whether roflumilast would reduce the frequency of exacerbations requiring corticosteroids in patients with COPD. Methods In two placebo-controlled, double-blind, multicentre trials (M2-124 and M2-125) with identical design that were done in two different populations in an outpatient setting, patients with COPD older than 40 years, with severe airflow limitation, bronchitic symptoms, and a history of exacerbations were randomly assigned to oral roflumilast (500 μg once per day) or placebo for 52 weeks. Primary endpoints were change in prebronchodilator forced expiratory volume in 1 s (FEV1 ) and the rate of exacerbations that were moderate (glucocorticosteroid-treated) or severe. Analysis was by intention to treat. The trials are registered with ClinicalTrials.gov , number NCT00297102 for M2-124, and NCT00297115 for M2-125. Findings Patients were assigned to treatment, stratified according to smoking status and treatment with longacting β2 agonists, and given roflumilast (n=1537) or placebo (n=1554). In both studies, the prespecified primary endpoints were achieved and were similar in magnitude. In a pooled analysis, prebronchodilator FEV1 increased by 48 mL with roflumilast compared with placebo (p<0·0001). The rate of exacerbations that were moderate or severe per patient per year was 1·14 with roflumilast and 1·37 with placebo (reduction 17% [95% CI 8–25], p<0·0003). Adverse events were more common with roflumilast (1040 [67%]) than with placebo (963 [62%]); 219 (14%) patients in the roflumilast group and 177 (12%) in the placebo group discontinued because of adverse events. In the pooled analysis, the difference in weight change during the study between the roflumilast and placebo groups was −2·17 kg. Interpretation Since different subsets of patients exist within the broad spectrum of COPD, targeted specific therapies could improve disease management. This possibility should be explored further in prospective studies. Funding Nycomed.
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1Administration, Oral
2Adrenergic beta-Agonists - therapeutic use
3Aged
4air flow
5Aminopyridines - pharmacology
6Aminopyridines - therapeutic use
7Analysis of Variance
8Benzamides - pharmacology
9Benzamides - therapeutic use
10Biological and medical sciences
11Cholinergic Antagonists - therapeutic use
12Chronic obstructive pulmonary disease
13Clinical trials
14Corticoids
15Cyclopropanes - pharmacology
16Cyclopropanes - therapeutic use
17Disease management
18Dosage and administration
19Double-Blind Method
20Drug therapy
21Drug Therapy, Combination
22Enzyme inhibitors
23Female
24Forced Expiratory Volume - drug effects
25General aspects
26Health economics
27Historical account
28Humans
29Internal Medicine
30Lung diseases, Obstructive
31Male
32Medical sciences
33Middle Aged
34Motivation
35Phosphodiesterase 4 Inhibitors
36Phosphodiesterase Inhibitors - pharmacology
37Phosphodiesterase Inhibitors - therapeutic use
38Proportional Hazards Models
39Pulmonary Disease, Chronic Obstructive - diagnosis
40Pulmonary Disease, Chronic Obstructive - drug therapy
41Pulmonary Disease, Chronic Obstructive - etiology
42Regression Analysis
43Respiratory function
44Severity of Illness Index
45Side effects
46Smoking
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48Studies
49Treatment Outcome
50Vital Capacity - drug effects
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titleRoflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials
authorCalverley, Peter MA, Prof ; Rabe, Klaus F, Prof ; Goehring, Udo-Michael, MD ; Kristiansen, Søren, PhD ; Fabbri, Leonardo M, Prof ; Martinez, Fernando J, Prof
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5Aminopyridines - pharmacology
6Aminopyridines - therapeutic use
7Analysis of Variance
8Benzamides - pharmacology
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abstractSummary Background The phosphodiesterase-4 inhibitor roflumilast can improve lung function and prevent exacerbations in certain patients with chronic obstructive pulmonary disease (COPD). We therefore investigated whether roflumilast would reduce the frequency of exacerbations requiring corticosteroids in patients with COPD. Methods In two placebo-controlled, double-blind, multicentre trials (M2-124 and M2-125) with identical design that were done in two different populations in an outpatient setting, patients with COPD older than 40 years, with severe airflow limitation, bronchitic symptoms, and a history of exacerbations were randomly assigned to oral roflumilast (500 μg once per day) or placebo for 52 weeks. Primary endpoints were change in prebronchodilator forced expiratory volume in 1 s (FEV1 ) and the rate of exacerbations that were moderate (glucocorticosteroid-treated) or severe. Analysis was by intention to treat. The trials are registered with ClinicalTrials.gov , number NCT00297102 for M2-124, and NCT00297115 for M2-125. Findings Patients were assigned to treatment, stratified according to smoking status and treatment with longacting β2 agonists, and given roflumilast (n=1537) or placebo (n=1554). In both studies, the prespecified primary endpoints were achieved and were similar in magnitude. In a pooled analysis, prebronchodilator FEV1 increased by 48 mL with roflumilast compared with placebo (p<0·0001). The rate of exacerbations that were moderate or severe per patient per year was 1·14 with roflumilast and 1·37 with placebo (reduction 17% [95% CI 8–25], p<0·0003). Adverse events were more common with roflumilast (1040 [67%]) than with placebo (963 [62%]); 219 (14%) patients in the roflumilast group and 177 (12%) in the placebo group discontinued because of adverse events. In the pooled analysis, the difference in weight change during the study between the roflumilast and placebo groups was −2·17 kg. Interpretation Since different subsets of patients exist within the broad spectrum of COPD, targeted specific therapies could improve disease management. This possibility should be explored further in prospective studies. Funding Nycomed.
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pubElsevier Ltd
pmid19716960
doi10.1016/S0140-6736(09)61255-1