Tiotropium treatment for bronchiectasis: a randomised, placebo-controlled, crossover trial

Abstract

Tiotropium via HandiHaler® is an established long-acting, anticholinergic bronchodilator that prevents exacerbations and improves lung function in patients with COPD. We hypothesized that tiotropium would reduce pulmonary exacerbations and improve lung function in patients with stable bronchiectasis and airflow limitation, and assessed the effect of tiotropium on these outcomes. In a randomised, double-blind, 2-period crossover trial, we recruited adult patients from 3 hospitals in New Zealand. Patients were excluded if they had a smoking history of more than 20 pack years. Patients were assigned to either the tiotropium-placebo or placebo-tiotropium sequence in a 1:1 ratio, using randomly permuted blocks stratified by centre. Participants and investigators were masked to treatment allocation. Eligible patients received tiotropium 18mcg via the HandiHaler® device daily for 6 months followed by 6 months of placebo, or vice versa, with a washout period of 4 weeks. The primary endpoint was rate of event-based exacerbations during the 6-month period. Primary analyses were carried out in an intention-to-treat set. Ninety patients were randomly assigned and 85 completed both treatment cycles. The rate of exacerbations under the tiotropium treatment was 2.17 y−1 and 2.27 y−1 under placebo (rate ratio 0.96, 95% CI 0.72–1.27; p=0.77). Tiotropium, as compared with placebo, improved FEV1 by 58 mL (95% CI 23–92; p=0.002). Adverse events were similar under both treatments. Tiotropium via HandiHaler® over 6 months significantly improved lung function but not frequency of exacerbations. Further research is required to understand the clinical context and significance of these findings.