The TRIFLOW study; A randomised, cross-over study evaluating the effects of inhaled beclometasone/formoterol/glycopyrronium (BDP/F/G) on hyperinflation in COPD

Abstract

Background: The effects of triple therapy on hyperinflation in COPD have not been investigated thoroughly. We evaluated the effects of the G and F components of the extrafine single inhaler triple therapy BDP/F/G pMDI on hyperinflation.

Methods: This open‑label, randomised, single centre, 2-way cross-over study recruited 23 COPD patients taking ICS based combination treatment and with residual volume (RV) > 120% predicted at screening. Inhaled BDP was taken during run-in and washout periods. Baseline lung function was measured over 12 hours prior to randomisation to BDP/F/GB or BDP/F for 5 days followed by washout and crossover. Lung function (spirometry, lung volumes, oscillometry) was measured prior to dosing on day 1 and for 12 hours post-dose on day 5.

Results: Co-primary endpoint analysis: BDP/F/G had a greater effect than BDP/F on FEV1 AUC0-12 (mean difference 104mls, p=0.0071) and RV AUC0-12 (mean difference -163mls, p=0.0028). Oscillometry measurements showed a greater effect of BDP/F/G on R5-R20 AUC0-12, which measures small airway resistance (mean difference -0.045 kPa/L/s, p=0.0002). Comparison of BDP/F with the baseline measurements (BDP alone) showed that F increased FEV1 AUC0-12 (mean difference 227mls) and improved RV AUC0-12 (mean difference -558mls) and R5-R20 AUC0-12 (mean difference -0.117 kPa/L/s), all p<0.0001.

Conclusions: In COPD patients with hyperinflation, the G and F components of extrafine BDP/F/G improved FEV1, RV and small airway function. This indicates that these bronchodilator components target small airway function, thereby improving lung volumes and airflow.