Magnussen 2008.
Methods | Design: randomised, double‐blind, placebo‐controlled study with 12 weeks treatment duration, conducted at 67 centres distributed within Belgium, Canada, Germany, Denmark, France, Italy, the Netherlands, and South Africa | |
Participants |
Population: 472 patients with COPD, as defined by GOLD guidelines, were randomised to tiotropium (228) and placebo (244) Baseline Characteristics: mean age 60 years, 61% male, mean FEV1 1.5 L, mean FEV1 predicted 53%, 34 pack‐years smoking history Inclusion Criteria: patients were required to have a physician‐diagnosis of asthma (before the age of 30 years), a diagnosis of COPD, post‐bronchodilator FEV1 < 80% predicted normal and a post‐bronchodilator ratio of FEV1/FVC < 70%. Other inclusion criteria were: smoking history > 10 pack‐years, age ≥ 40 years, treatment with ICS for ≥ 1 year prior to study entry, and an acute bronchodilator response ≥ 200 ml and ≥ 12% of pre‐bronchodilator FEV1 at the screening visit or documented during the past five years in the patient clinic records |
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Interventions |
1. Tiotropium 18 mcg once daily 2. Placebo once daily Inhaler device: dry powder inhaler Co‐medication: patients were allowed to continue treatment with inhaled LABAs, ICS, oral steroids (≤ 10 mg/day prednisone or equivalent), theophyllines, leukotriene antagonists, and cromones as concomitant medication. Salbutamol was provided for as‐needed acute symptom relief. Patients were not allowed to take anticholinergic therapy other than study drug during the randomisation period |
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Outcomes | Spirometry: FEV1 and FVC area under the curve (AUC) 0‐6h, PEFR, symptom relief: rescue medication use | |
Notes |
Funding: Boehringer Ingelheim Study number: Boehringer Ingelheim 205.301, ClinicalTrials.gov NCT00152984 Definitions: an exacerbation of COPD and asthma was defined as an adverse event which was a worsening of disease meeting the criteria for an serious adverse event, or led to treatment discontinuation, or required changed concomitant medication, or was an unexpected deterioration from baseline |
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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 | Withdrawal rates were low (tiotropium 2.2%, placebo 4.5%) |
Selective reporting (reporting bias) | Low risk | Results for all specified outcomes were reported |