Journal Article

Concurrent use of indacaterol plus tiotropium in patients with COPD provides superior bronchodilation compared with tiotropium alone: a randomised, double-blind comparison

Mahler, Donald A, Bateman, Eric D, Lassen, Cheryl, D'Urzo, Anthony, White, Tracy, Özkan, Serir A, Peckitt, Clare, Kramer, Benjamin

2012

Overview

BackgroundCurrent guidelines recommend treatment with one or more long-acting bronchodilators for patients with moderate or more severe chronic obstructive pulmonary disease (COPD). The authors investigated the approach of dual bronchodilation using indacaterol, a once-daily long-acting β2 agonist, and the long-acting muscarinic antagonist tiotropium, compared with tiotropium alone.MethodsIn two identically designed, double-blind, 12-week studies, patients with moderate to severe COPD were randomised to indacaterol 150 μg once daily or matching placebo. All patients concurrently received open-label tiotropium 18 μg once daily. The primary outcome was standardised area under the curve of forced expiratory volume in 1 s (FEV1) from 5 min to 8 h post dose at week 12. The key secondary outcome was 24 h post-dose (‘trough’) FEV1 at week 12. Resting inspiratory capacity (IC) was measured in a subgroup.Results1134 and 1142 patients were randomised in studies 1 and 2; 94% and 94% completed. Compared with monotherapy, concurrent therapy increased FEV1 (area under the curve by 130 and 120 ml, trough by 80 and 70 ml; all p<0.001) and trough IC (by 130 and 100 ml, p<0.01). Cough was more common with indacaterol plus tiotropium (10% and 9%) than with tiotropium alone (4% and 4%). Most cases (∼90%) of cough were mild. Other adverse events were similar for the treatment groups.ConclusionsCompared with tiotropium monotherapy, indacaterol plus tiotropium provided greater bronchodilation and lung deflation (reflected by increased resting IC). Adverse events were similar between treatments apart from mild cough being more common with indacaterol plus tiotropium. These results support COPD guideline recommendations to combine bronchodilators with different mechanisms of action.Trial registration numbersNCT00846586 and NCT00877383.

• Publisher: BMJ Publishing Group Ltd and British Thoracic Society,BMJ Publishing Group,BMJ Publishing Group LTD
• Subject: Adrenergic beta-Agonists - therapeutic use / Adult / Analysis of Variance / Area Under Curve / asthma / asthma epidemiology / asthma guidelines / asthma in primary care / asthma pharmacology / Biological and medical sciences / Bronchodilator Agents - therapeutic use / Cardiology. Vascular system / chronic obstructive / Chronic obstructive pulmonary disease / Chronic obstructive pulmonary disease, asthma / COPD epidemiology / COPD exacerbations / COPD mechanisms / COPD pharmacology / Double-Blind Method / Drug Therapy, Combination / Effectiveness / exercise / Female / Humans / Indacaterol / Indans - therapeutic use / inhaler devices / Least-Squares Analysis / lung cancer / Male / Medical sciences / Middle Aged / Patients / perception of asthma/breathlessness / Placebos / pleural disease / Pneumology / pulmonary disease / Pulmonary Disease, Chronic Obstructive - drug therapy / Pulmonary Disease, Chronic Obstructive - physiopathology / pulmonary embolism / Quinolones - therapeutic use / Respiratory Function Tests / Scopolamine Derivatives - therapeutic use / Severity of Illness Index / tiotropium / Tiotropium Bromide / Treatment Outcome / tuberculosis