Cilomilast 110
Study characteristics
Methods Study design: parallel-group study
Randomisation: randomised, double-blind, placebo-controlled trial
Trial duration: 12 weeks
Analysis was done on per-protocol population
Participants Setting: 10 centres in the USA
Participants: 65 (15 mg cilomilast: 31, placebo: 34)
Baseline characteristics: mean age 64.4 years placebo and 66.1 years cilomilast, 67% male placebo
and 84% male cilomilast, mean FEVD % predicted not available
Inclusion criteria: aged 40 to 80 years, FEVD/FVC Z 0.7 with smoking history > 10 pack-years, postsalbutamol
reversibility Z 15% or 200 mL, post-salbutamol FEVD ^ 1.0 L and between 30% and 70% predicted
Exclusion criteria: not stated
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Total numbers of participant withdrawals: 1 (3%) and 1 (3%) from treatment and control groups,
respectively
Interventions Run-in: not stated
• Cilomilast 15 mg twice daily
• Placebo twice daily
Concomitant medication
• Short-acting anticholingeric: no information available
• SABA: no information available
• Corticosteroid: no information available
• LABA: no information available
Outcomes Primary outcome: change from baseline at endpoint in neutrophils as a percentage of total cells
in induced
sputum
Secondary outcomes: FVC at trough; sputum macrophages, eosinophils, and lymphocytes as a
percentage
of total cells in induced sputum; total cell counts in induced sputum
Notes Funded by GlaxoSmithKline
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation
(selection bias)
Low risk Assumed that trialists used a robust method to carry out the randomisation
process because of pharmaceutical sponsorship
Allocation concealment
(selection bias)
Low risk Assumed that trialists used a robust method to carry out the randomisation
process because of pharmaceutical sponsorship
Blinding of participants
and personnel (performance
bias)
All outcomes
Low risk The trial was double-blinded
Blinding of outcome assessment
(detection bias)
All outcomes
Low risk Assumed that this would be low risk; however, no available information
Incomplete outcome data
(attrition bias)
All outcomes
Low risk Total numbers of participants withdrawn 1 (3%) placebo, 1 (3%) cilomilast
Selective reporting (reporting
bias)
Low risk Outcomes were reported as planned. Trial information was reported on the
GSK website only
Other bias Unclear risk No information on baseline anticholinergic, betaT-agonist, or corticosteroid
Use
Study characteristics
Methods Study design: parallel-group study
Randomisation: randomised, double-blind, placebo-controlled trial
Trial duration: 24 weeks
Intention-to-treat analysis: stated
Participants Setting: 43 centres in mainland China, Hong Kong, and Singapore
Participants: 626 (500 Gg roflumilast: 313, placebo: 313)
RO-2455-301-RD (ACROSS)_
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Baseline characteristics: mean age 64 years, 91% male, mean FEVD % predicted 36%, mean smoking
history 37.2 pack-years for roflumilast and 37.5 pack-years for placebo or current smokers (24% and
29%, respectively)
Inclusion criteria: Chinese, Malaysian, or Indian ethnicity, age 40 to 80 years with severe or very severe
COPD, FEVD/FVC Z 0.7, post-bronchodilator FEVD Z 50%. Current smokers or ex-smokers with smoking
history > 10 pack-years or current smokers; 12-month history of COPD and ^ 14 puKs of rescue medication
during the week before randomisation
Exclusion criteria: primary bronchiectasis, cystic fibrosis, bronchiolitis, lung resection, lung cancer,
interstitial
lung disease, active TB, lower respiratory tract infection, diagnosis of asthma at < 40 years of
age, iD-antitrypsin deficiency
Total numbers of participant withdrawals: 67 (21.4%) and 50 (16%) from treatment and control
groups, respectively
Interventions Run-in: 4 weeks, single-blind. Placebo tablets to assess suitability
• Roflumilast 500 Gg once daily
• Placebo once daily
Concomitant medication
Participants were allowed to continue taking fixed combinations of ICS plus LABA or LAMA monotherapy
(e.g. tiotropium) if taken at a stable dose for at least 6 months before the run-in period. SAMAs (e.g.
ipratropium) were allowed at a constant daily dose as concomitant medication if taken on a regular basis
for at least 4 weeks before study inclusion. All other COPD treatments were not allowed
Outcomes Primary outcomes: lung function; change in pre-bronchodilator FEVD
Secondary outcomes: changes in post-bronchodilator FEVD, FVC, incidence rates of COPD
exacerbations,
time to first COPD exacerbation, transition dyspnoea index, proportions of participants experiencing
a COPD exacerbation, adverse events, changes in body weight, laboratory values, vital signs,
and physical examination findings
Notes Clinicaltrials.gov identifier: NCT01313494
Funded by AstraZeneca
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation
(selection bias)
Low risk Investigators used an automated, interactive voice-response system to randomly
assign participants. The sponsor generated a list of participant numbers
using a pseudo-random number generator
Allocation concealment
(selection bias)
Low risk The investigator or anyone at the study site was prevented from knowing the
allocation sequence with code labelling
Blinding of participants
and personnel (performance
bias)
All outcomes
Low risk The trial was double-blinded, and tablets were identical in appearance
Blinding of outcome assessment
(detection bias)
All outcomes
Low risk The trial was double-blinded. The investigator or anyone at the study site was
prevented from knowing the treatment allocation
Incomplete outcome data
(attrition bias)
Low risk Total numbers of participants that discontinued 50 (16%) placebo, 67 (21.4%)
roflumilast
RO-2455-301-RD (ACROSS)_4(Continued)
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All outcomes
Selective reporting (reporting
bias)
Unclear risk Outcomes were reported as planned, and the trial was registered at the NCT
website
Other bias Low risk LAMA: 17.9% for placebo; 20.4% for roflumilast
SAMA: 18.2% for placebo; 17.3% for roflumilast
ICS/LABA: 55.9% for placebo; 59.7% for roflumilast
No information available. SABA allowed