Cooper 2010.
| Methods | Design: A randomised, parallel group, double‐blind, placebo‐controlled study with 96 weeks (two years) treatment duration, conducted in 60 centres | |
| Participants |
Population: 519 patients with COPD were randomised to tiotropium (260) and placebo (259) Baseline Characteristics: mean age 65 years, 77% male, mean FEV1 1.1 L, mean FEV1 predicted 38%, 52 pack‐years smoking history Inclusion Criteria: male or female, ≥ 40 years old, with a diagnosis of COPD (pre‐bronchodilator FEV1 ≤ 60% predicted, post‐bronchodilator FEV1 ≤ 65% predicted, FEV1/FVC < 70%), smoking history ≥ 10 pack‐years Exclusion Criteria: history of asthma |
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| Interventions |
1. Tiotropium 18 mcg oral inhalation 2. Placebo oral inhalation Inhaler device: dry powder inhaler Co‐medication: concomitant use of theophylline preparations, mucolytics, ICS, LABAs and oral steroids was allowed. During the treatment period, patients were not allowed to use antileukotrienes, cromolyns, antibiotics, antileukotrienes, long‐acting anticholinergics, or any other investigational drug. |
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| Outcomes |
Primary: Endurance Time (ET) including secondary endpoint ET at visits 4 to 9 and post‐hoc analysis (90% of maximum work rate treadmill ET Secondary: ET at 100 weeks, pulmonary function tests, Lung function (FEV1, FVC), Quality of life SGRQ, Modified Borg scale, exacerbations of COPD, Physician’s and Patient’s Global Evaluation |
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| Notes |
Funding: Boehringer Ingelheim Study number: Boehringer Ingelheim 205.368, ClinicalTrials.gov NCT00525512 Definitions: COPD exacerbations defined as a complex of respiratory symptoms (increase or new onset) of more than 1 of the following: cough, sputum, wheezing, dyspnoea, or chest tightness with a duration of at least three days requiring treatment with antibiotics and/or systemic steroids and/or hospital admission. |
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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 | A third‐party Interactive Voice Response System was used to randomise patients via a unique randomisation number to study drug medication |
| 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 | High risk | Withdrawal rates were relatively high and uneven (tiotropium 27.3%, placebo 39.0%) |
| Selective reporting (reporting bias) | Low risk | Results for all specified outcomes were reported |