Triple therapy reduces exacerbations in patients with symptomatic COPD


Clinical Question: Does triple therapy (long-acting beta2-agonist, long-acting muscarinic antagonist, and inhaled corticosteroid) reduce exacerbations in patients with symptomatic chronic obstructive pulmonary disease (COPD)?

Background: Guidelines from GOLD and NICE recommend considering a step-up to triple therapy for patients with refractory COPD symptoms or exacerbations. However, it is unknown if this reduces the long term risk of exacerbations.

Study Design: A randomized controlled trial.

Setting: Facilities consisting of 224 primary and specialty care sites in fifteen countries.

Synopsis: This study enrolled 2,691 patients with COPD, severe airflow restriction (FEV1 less than 50%), significant symptoms (CAT score greater than or equal to 10), and at least one exacerbation in the past year. Participants were randomized to a novel three-agent inhaler (containing an extrafine formulation of beclomethasone, formoterol, and glycopyrronium), an “open triple” regimen including beclomethasone/formoterol plus tiotropium, or to tiotropium alone.

During 52 weeks of treatment, the triple therapy regimens significantly reduced moderate to severe COPD exacerbations, compared with tiotropium alone, with annualized exacerbation rates of 0.46 (95% confidence interval, 0.41-0.51), 0.45 (0.39-0.52), and 0.57 (0.52-0.63), respectively. Rates of adverse events were similar between all three groups.

Bottom Line: Triple therapy was superior to tiotropium alone for reducing exacerbations in patients with symptomatic COPD. The two triple therapy regimens studied did not significantly differ in efficacy.

Citation: Vestbo J, Papi A, Corradi M, et al. Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): A double-blind, parallel group, randomized controlled trial. Lancet. 2017;389(10082):1919-29.

Dr. Troy is assistant professor in the University of Kentucky division of hospital medicine.

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