Concurrent use of indacaterol plus tiotropium in patients with COPD provides superior bronchodilation compared with tiotropium alone: a randomised, double-blind comparison
- Donald A Mahler1,2,
- Anthony D'Urzo3,
- Eric D Bateman4,
- Serir A Özkan5,
- Tracy White6,
- Clare Peckitt7,
- Cheryl Lassen7,
- Benjamin Kramer6,
- on behalf of the INTRUST-1 and INTRUST-2 study investigators
- 1Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School, Hanover, New Hampshire, USA
- 2Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
- 3Department of Family and Community Medicine (DFCM), University of Toronto, Toronto, Canada
- 4Division of Pulmonology, Department of Medicine, University of Cape Town, Cape Town, South Africa
- 5Division of Pulmonary Medicine, Izmir Training Hospital for Pulmonary Medicine and Surgery, Izmir, Turkey
- 6Novartis Pharmaceuticals, East Hanover, New Jersey, USA
- 7Novartis Horsham Research Centre, Horsham, West Sussex, UK
- Correspondence to Dr Donald A Mahler, Section of Pulmonary and Critical Care Medicine, 5C Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756-0001, USA;
Contributors All authors had access to the study data, were involved in interpretation and/or presentation of the data for this report, reviewed and revised the initial draft and subsequent versions of the manuscript, had final responsibility for the decision to submit for publication and approved the version submitted.
- Received 21 September 2011
- Accepted 29 March 2012
- Published Online First 27 April 2012
Background Current 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.
Methods In 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.
Results 1134 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.
Conclusions Compared 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 numbers NCT00846586 and NCT00877383.
- pulmonary disease
- chronic obstructive
- COPD mechanisms
- COPD exacerbations
- COPD pharmacology
- perception of asthma/breathlessness
- asthma epidemiology
- asthma guidelines
- asthma in primary care
- asthma pharmacology
- COPD epidemiology
- inhaler devices
- COPD exacerbations
- lung cancer
- pleural disease
- pulmonary embolism
Funding The study was funded by Novartis Pharma AG, the manufacturer of indacaterol. Novartis designed the study and analysed the data. Data were recorded at participating clinical centres and maintained by Novartis.
Competing interests DAM has received remuneration for participation in advisory boards and/or consulting from AstraZeneca, Boehringer-Ingelheim, DeepBreeze, Forest, GlaxoSmithKline, Merck, Nycomed, Novartis, and Sunovion. AD has received research, consulting and lecturing fees from GlaxoSmithKline, Sepracor, Schering Plough, Altana, Methapharma, AstraZeneca, ONO pharma, Novartis Canada/USA, Hoffmann-La Roche Limited, and KOS Pharmaceuticals. EDB has received remuneration for lectures, participation in advisory boards and/or consulting from Amgen, Almirall, Alk Abello, Actelion, AstraZeneca, Boehringer Ingelheim, Elevation Pharma, Forest, GlaxoSmithKline, Merck, Nycomed, Novartis and Pfizer. SAÖ has received research grants from Novartis and Boehringer-Ingelheim. TW, CP, CL and BK are employees of Novartis, the study sponsor.
Patient consent Patients gave their written informed consent to participate before receiving any study treatment. Patients are not identifiable by the information given in the manuscript.
Ethics approval The study design was approved by independent ethics committees or review boards at each centre. Patients gave their written informed consent to participate before receiving any study treatment.
Provenance and peer review Not commissioned; externally peer reviewed.