The TRIFLOW study: a randomised, cross-over study evaluating the effects of extrafine beclometasone/formoterol/glycopyrronium on gas trapping in COPD

James Dean, Catalina Panainte, Naimat Khan, Dave Singh, James Dean, Catalina Panainte, Naimat Khan, Dave Singh

Abstract

Background: The effects of triple therapy on gas trapping in COPD are not fully understood. We evaluated the effects of the long acting bronchodilator components of the extrafine single inhaler triple therapy beclometasone dipropionate/formoterol/glycopyrronium (BDP/F/G) pMDI on gas trapping.

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

Results: Co-primary endpoint analysis: BDP/F/G had a greater effect than BDP/F on FEV1 area under the curve over 12 h (AUC0-12) (mean difference 104 mls, p = 0.0071) and RV AUC0-12 (mean difference - 163 mls, p = 0.0028). Oscillometry measurements showed a greater effect of BDP/F/G on the difference between resistance at 5 and 20 Hz (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 227 mls) and improved RV AUC0-12 (mean difference - 558 mls) 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. These long acting bronchodilators target small airway function, thereby improving gas trapping and airflow. Trial registration The study was retrospectively registered at ClinicalTrials.gov on 15th February 2019 (No.: NCT03842904, https://ichgcp.net/clinical-trials-registry/NCT03842904 ).

Keywords: COPD; Oscillometry; Small airways; Triple therapy.

Conflict of interest statement

JD; The author declares that they have no competing interests. CP; The author declares that they have no competing interests. NK; The author declares that they have no competing interests. DS has received sponsorship to attend international meetings, honoraria for lecturing or attending advisory boards and research grants from various pharmaceutical companies including AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Menarini, Mundipharma, Novartis, Peptinnovate, Pfizer, Pulmatrix, Therevance and Verona.

Figures

Fig. 1
Fig. 1
Study design. BDP beclometasone dipropionate, F formoterol, G glycopyrronium
Fig. 2
Fig. 2
Patient flow through the study. BDP beclometasone dipropionate, F formoterol, G glycopyrronium
Fig. 3
Fig. 3
Mean FEV1 change on day 5 compared to Day 1 pre-dose value. Bars are 95% confidence intervals. BDP beclometasone dipropionate, F formoterol, G glycopyrronium
Fig. 4
Fig. 4
Mean residual volume (RV) change on day 5 compared to Day 1 pre-dose value. Bars are 95% confidence intervals. BDP beclometasone dipropionate, F formoterol, G glycopyrronium

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Source: PubMed

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