Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double-blind, parallel group, randomised controlled trial

• Published in: The Lancet (British edition) Vol. 389; no. 10082; pp. 1919 - 1929
• Main Authors: Vestbo, Jørgen, Prof, Papi, Alberto, Prof, Corradi, Massimo, Prof, Blazhko, Viktor, MD, Montagna, Isabella, MSc, Francisco, Catherine, MSc, Cohuet, Géraldine, MSc, Vezzoli, Stefano, MSc, Scuri, Mario, MD, Singh, Dave, Prof
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 13.05.2017; Elsevier Limited
• Subjects: Acetylcholine receptors (muscarinic); Acute coronary syndromes; Air flow; Angina pectoris; Antagonist drugs; Bronchodilators; Cardiomyopathy; Cardiovascular disease; Chronic obstructive pulmonary disease; Clinical trials; Coronary vessels; Corticosteroids; Disease control; Dosage; Double-blind studies; Evidence-based medicine; Formoterol; Heart attacks; Inhalation; Inhalers; Interactive systems; Internal Medicine; Lung diseases; Obstructive lung disease; Patients; Pneumonia; Population; Powder; Quality of life; Randomization; Respiration; Respiratory therapy; Therapy; Germany
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(17)30188-5

Summary Background Limited data are available for the efficacy of triple therapy with two long-acting bronchodilators and an inhaled corticosteroid in chronic obstructive pulmonary disease (COPD). We compared treatment with extrafine beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB; fixed triple) with tiotropium, and BDP/FF plus tiotropium (open triple). Methods For this double-blind, parallel-group, randomised, controlled trial, eligible patients had COPD, post-bronchodilator forced expiratory volume in 1 s (FEV1 ) of less than 50%, at least one moderate-to-severe COPD exacerbation in the previous 12 months, and a COPD Assessment Test total score of at least 10. After a 2-week run-in period receiving one inhalation per day via single-dose dry-powder inhaler of open-label 18 μg tiotropium, patients were randomised (2:2:1) using a interactive response technology system to 52 weeks treatment with tiotropium, fixed triple, or open triple. Randomisation was stratified by country and severity of airflow limitation. The primary endpoint was moderate-to-severe COPD exacerbation rate. The key secondary endpoint was change from baseline in pre-dose FEV1 at week 52. The trial is registered with ClinicalTrials.gov , number NCT01911364. Findings Between Jan 21, 2014, and March 18, 2016, 2691 patients received fixed triple (n=1078), tiotropium (n=1075), or open triple (n=538). Moderate-to-severe exacerbation rates were 0·46 (95% CI 0·41–0·51) for fixed triple, 0·57 (0·52–0·63) for tiotropium, and 0·45 (0·39–0·52) for open triple; fixed triple was superior to tiotropium (rate ratio 0·80 [95% CI 0·69–0·92]; p=0·0025). For week 52 pre-dose FEV1 , fixed triple was superior to tiotropium (mean difference 0·061 L [0·037 to 0·086]; p<0·0001) and non-inferior to open triple (−0·003L [–0·033 to 0·027]; p=0·85). Adverse events were reported by 594 (55%) patients with fixed triple, 622 (58%) with tiotropium, and 309 (58%) with open triple. Interpretation In our TRINITY study, treatment with extrafine fixed triple therapy had clinical benefits compared with tiotropium in patients with symptomatic COPD, FEV1 of less than 50%, and a history of exacerbations. Funding Chiesi Farmaceutici SpA.