Evidence map›Paper›PMID 19716961›Full record

Trial reportLancet (London, England)2009

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

Leonardo M Fabbri, Peter M A Calverley, José Luis Izquierdo-Alonso, Daniela S Bundschuh, Manja Brose, Fernando J Martinez, Klaus F Rabe, M2-127 and M2-128 study groups

3 registry-linked trialsOpen access · greenAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Lancet (London, England), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 176 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
176citing papers in PubMed, 10 pooled it
53.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00313209 phase3completednot on this map

Effect of Roflumilast in COPD Patients Treated With Salmeterol. A 24-week, Double-blind Study With 500 μg Roflumilast Once Daily Versus Placebo. The EOS Study

TypeinterventionalSponsorAstraZenecaRan2006 to 2008Enrolled933ConditionsChronic Obstructive Pulmonary Disease (COPD)ArmsRoflumilast, Placebo
NCT00424268 phase3completednot on this map

Effect of Roflumilast in COPD Patients Treated With Tiotropium. A 24-week, Double-blind Study With 500 µg Roflumilast Once Daily Versus Placebo. The HELIOS Study

TypeinterventionalSponsorAstraZenecaRan2007 to 2008Enrolled743ConditionsChronic Obstructive Pulmonary DiseaseArmsRoflumilast, Placebo
NCT01701934 phase2terminatednot on this mapstarted 2013, after this paper: background citation

Impact of Roflumilast on Visceral Adiposity and MetaBolic Profile in Chronic Obstructive Lung Disease: a Randomized and Controlled Trial: the RAMBO Trial.

TypeinterventionalSponsorLaval UniversityRan2013 to 2014Enrolled14ConditionsChronic Obstructive Pulmonary Disease, Metabolic SyndromeArmsRoflumilast, Placebo
3 · Its place in the literature

Who cites it

176 citing papers in PubMed, 10 syntheses or guidelines pooled it, 606 citations in OpenAlex.

  1. Pooled it
  2. Phosphodiesterase-4 inhibitors for chronic obstructive pulmonary disease.The Cochrane database of systematic reviews · 2020
    Pooled it
  3. Pooled it
  4. Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease.The Cochrane database of systematic reviews · 2017
    Pooled it
  5. Pooled it
  6. Pooled it
  7. Potential treatment benefits and safety of roflumilast in COPD: a systematic review and meta-analysis.International journal of chronic obstructive pulmonary disease · 2016
    Pooled it
  8. Pooled it
  9. Pooled it
  10. Guideline
  11. Trial
  12. Trial
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  16. Adherence to roflumilast under dose-escalation strategy in Korean patients with COPD.International journal of chronic obstructive pulmonary disease · 2019
    Trial
  17. Trial
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  19. Trial
  20. Use of a 4-week up-titration regimen of roflumilast in patients with severe COPD.International journal of chronic obstructive pulmonary disease · 2018
    Trial

116 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 5 countries.

Leonardo M FabbriUniversity of Modena and Reggio Emilia, Modena, Italy.
Peter M A Calverley
José Luis Izquierdo-Alonso
Daniela S Bundschuh
Manja Brose
Fernando J Martinez
Klaus F Rabe
M2-127 and M2-128 study groups
Hospital Universitario de Guadalajara · ESLeiden University Medical Center · NLLiverpool School of Tropical Medicine · GBMichigan Medicine · USUniversity of Modena and Reggio Emilia · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPatients 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.

methodsIn 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.

findingsIn 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.

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

fundingNycomed.

Indexed as

Administration, InhalationAdministration, OralAgedAlbuterolAminopyridinesAnalysis of VarianceBenzamidesBronchodilator AgentsCyclopropanesDouble-Blind MethodDrug Therapy, CombinationFemaleForced Expiratory VolumeHumansMaleMiddle AgedAlbuterolAminopyridinesBenzamidesBronchodilator AgentsCyclopropanesPhosphodiesterase 4 InhibitorsPhosphodiesterase InhibitorsRoflumilastSalmeterol XinafoateScopolamine DerivativesTiotropium Bromide

Identifiers

PMID19716961
OpenAlexW2097243317

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.