NCT00144326.

Methods	Design: randomised, double‐blind, placebo‐controlled, parallel‐group, multicentre study with 12 weeks treatment duration
Participants	Population: 250 patients with COPD were randomised to tiotropium (123) and placebo (127) Baseline Characteristics: mean age 63 years, 78% male, mean FEV1 1.3 L, mean FEV1 predicted 46% Inclusion Criteria: ambulatory patients of either sex; > 40 years old, diagnosed with COPD (FEV1 < 60% of the predicted value and FEV1/FVC < 70%); smokers or ex‐smokers with a history of having smoked at least 10 pack‐years
Interventions	1. Tiotropium 18 mcg once daily by oral inhalation 2. Placebo once daily by oral inhalation Inhaler device: dry powder inhaler Co‐medication: patients were permitted to use SABAs, as needed, for acute symptom relief. Concomitant use of theophylline preparations, mucolytics, ICS, antibiotics, antihistamines, and oral steroids was allowed. During the treatment period, patients were not allowed to use beta‐blockers, cromolyns, antileukotrienes, inhaled LABAs, long‐acting anticholinergics, or any other investigational drug
Outcomes	Primary: difference in daily physical activity measured in vector magnitude units (VMUs) by the triaxial Stayhealthy RT3 accelerometer at the end of the treatment period Secondary: the difference in physical activity measured in VMUs by the triaxial Stayhealthy RT3 accelerometer at 1 month and 2 month treatment period, trough (10±3 minutes predose) FEV1, peak FEV1 as measured by the maximum post‐bronchodilator value obtained within 2 hours of testing on study days (30±5, 60±10, and 120±10 minutes), trough and peak SVC measured at the same time as the FEV1 on each study day, trough and peak inspiratory capacity (IC) measured at the same time as the FEV1 on each study day, trough and peak forced inspiratory volume in one second (FIV1) measured at the same time as the FEV1 on each study day, distance covered in the six‐minute walk distance (6MWD), modified Borg Dyspnoea Scale, quality of life as measured by the Chronic Respiratory Questionnaire (CRQ), use of salbutamol (rescue medication) during the treatment period, time point at which a 20% improvement from baseline in physical activity was achieved, physician’s Global Assessment
Notes	Funding: Boehringer Ingelheim Study number: Boehringer Ingelheim 205.269, ClinicalTrials.gov NCT00144326 Definitions: an exacerbation of COPD was defined as a complex of respiratory symptoms (two or more) COPD‐related (increased or new onset) with a duration of at least three days. COPD‐related respiratory symptoms consisted of cough, wheeze, dyspnoea, shortness of breath, chest tightness, or increase in production and/or purulence in sputum. These symptoms must have been accompanied with antibiotic treatment and/or systemic corticoids (oral, intramuscular or endovenous) or with a significant change in respiratory medication prescribed
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The randomisation list was generated by Boehringer Ingelheim using a validated system, which involved a pseudo‐random number generator so that the resulting treatment sequence was both reproducible and non‐predictable
Allocation concealment (selection bias)	Low risk	All investigational medication for each patient was identified by a unique medication number. Each eligible patient was assigned the lowest medication number available to the investigator at the time of randomisation
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Boehringer Ingelheim was responsible for preparing and coding study medication in a blinded fashion (Boehringer Ingelheim study drug and control were indistinguishable). Patients, investigators and study personnel remained blinded with regard to the treatment assignments up to database lock
Blinding of outcome assessment (detection bias) All outcomes	Low risk	In all studies, a selection of standard respiratory endpoints like pulmonary function, SGRQ, TDI, treadmill, exacerbations, etc. were used. Outcome assessors remained blinded with regard to the treatment assignments up to database lock
Incomplete outcome data (attrition bias) All outcomes	Low risk	The withdrawal rates were relatively low and even (tiotropium 8.1%, placebo 11.8%)
Selective reporting (reporting bias)	Low risk	No published report available, but results for all specified outcomes were supplied on request