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

RCT (N=2,691) found that compared with tiotropium, fixed triple therapy showed a 20% reduction in rate of moderate-to-severe COPD exacerbations (0.46 v 0.57 per patient/year, p=0.0025) together with an improvement in lung function, and was non-inferior to open triple therapy.

Fixed triple therapy consisted of beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB) in one devide, which was compared with tiotropium alone, and BDP/FF plus T (open triple) administered as two separate devices. Moderate-to-severe exacerbation rates for the open triple arm was 0.45 per patient per year.

 

In a related editorial, the authors comment that the major limitation of this study  was the low incidence of exacerbations. This result has two major implications for clinical practice. On one hand, it does not provide support for the current recommendation of triple LABA/LAMA/ICS therapy for patients with GOLD severity D, and on the other hand does provide evidence for the efficacy of triple therapy in patients currently defined as GOLD severity B.

 

The authors conclude that “properly designed randomised controlled trials should be done with triple therapy in patients with COPD of severity GOLD B who are often underrepresented in such trials i.e. patients who are elderly, frail, have multimorbidity, perhaps with the aim to test the effect of triple therapy on hospitalisation and survival, fundamental outcomes that are unfortunately not affected by any available pharmacological treatment of COPD.”