Trooster 2011.

Methods	Design: randomized, double‐blind, placebo‐controlled, multi‐national study Duration: 24 weeks Location: 62 centres in 10 countries
Participants	Population: 457 participants were randomised to tiotropium (238) and placebo (219) Baseline characteristics Age (mean years): tio 61.2, pbo 62.3 % Male: tio 69.7, pbo 67.1 % FEV1 predicted: not reported Pack‐years (mean): not reported Inclusion criteria: moderate COPD (post‐bronchodilator forced expiratory volume in 1 second [FEV1] 50‐80% predicted; GOLD Stage II) who have not previously been treated with maintenance therapy, i.e. who have only been treated with short‐acting b2agonists on an as‐needed basis in the 6 months prior to study enrolment and who have symptomatic shortness of breath. Exclusion criteria: (1) were treated with maintenance respiratory medications within the 6 months prior to screening; (2) had an upper respiratory tract infection or COPD exacerbation in the 6 weeks prior to the screening visit or during the screening visit prior to Visit 3; (3) had non‐pulmonary disease that would limit physical activity (e.g. arthritis, amputation); (4) had a history of asthma, cystic fibrosis, pulmonary fibrosis, bronchiectasis, pulmonary resection or other significant respiratory disorders other than COPD; (5) had significant diseases other than COPD which, in the opinion of the investigator, may influence the results of the study or the patient’s ability to participate; (6) contraindication to exercise testing; (7) had prior participation (within 2 years) of either cardiac or pulmonary rehabilitation
Interventions	1.Tiotropium 18 qd (LAMA) 2. Placebo (PBO Inhaler device: HandiHaler Allowed co‐medications: as‐needed albuterol. There was no restrictions for medications prescribed for treatment of exacerbations as long as they are used for fewer than 2 cumulative weeks
Outcomes	The primary endpoint is lung function improvement as captured by the area under the curve (AUC) of FEV1 versus time (FEV1AUC 0‐3h). Physical activity is assessed during the week prior to each study visit, using a validated activity monitor as a secondary endpoint. Additional secondary objectives include the effect of tiotropium treatment on other lung function variables, patient and physician global evaluations, worker productivity as assessed by the Work Productivity and Activity Impairment questionnaire, and the use of rescue medication. Information on COPD exacerbations is collected through serious adverse event monitoring.
Notes	Funding: Boehringer Ingelheim/Pfizer Identifier(s): NCT00523991 and 205.365, A4471008
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomized in a ratio of 1:1 [industry funded]
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind treatment phase. Placebo was delivered in an identical inhaler.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Low risk	Full Analysis Set (FAS): All subjects who were randomized, received at least 1 dose of the study drug, and had baseline and at least 1 post‐baseline data measurement available for the primary efficacy variable. All efficacy analyses, except analyses for physical activity endpoints, were performed using the FAS population (95% of those randomised). 89% and 90% completed the study.
Selective reporting (reporting bias)	Low risk	Results were well reported in the publication and posted on clinicaltrials.gov