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 |
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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 |
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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 |
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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 |
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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 |