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

Publisher: BioMed Central Ltd Country of Publication: England NLM ID: 101090633 Publication Model: Electronic Cited Medium: Internet ISSN: 1465-993X (Electronic) Linking ISSN: 14659921 NLM ISO Abbreviation: Respir Res Subsets: MEDLINE

Publication: 2001- : London : BioMed Central Ltd.
Original Publication: London : Current Science Ltd., c2000-

Adrenergic beta-2 Receptor Agonists/*administration & dosage ; Beclomethasone/*administration & dosage ; Bronchodilator Agents/*administration & dosage ; Formoterol Fumarate/*administration & dosage ; Glucocorticoids/*administration & dosage ; Glycopyrrolate/*administration & dosage ; Lung/*drug effects ; Muscarinic Antagonists/*administration & dosage ; Pulmonary Disease, Chronic Obstructive/*drug therapy; Administration, Inhalation ; Adrenergic beta-2 Receptor Agonists/adverse effects ; Adult ; Aged ; Beclomethasone/adverse effects ; Bronchodilator Agents/adverse effects ; Cross-Over Studies ; Drug Combinations ; England ; Female ; Forced Expiratory Volume ; Formoterol Fumarate/adverse effects ; Glucocorticoids/adverse effects ; Glycopyrrolate/adverse effects ; Humans ; Lung/physiopathology ; Male ; Middle Aged ; Muscarinic Antagonists/adverse effects ; Nebulizers and Vaporizers ; Particle Size ; Pulmonary Disease, Chronic Obstructive/diagnosis ; Pulmonary Disease, Chronic Obstructive/physiopathology ; Recovery of Function ; Time Factors ; Treatment Outcome

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 FEV 1 area under the curve over 12 h (AUC 0-12 ) (mean difference 104 mls, p = 0.0071) and RV AUC 0-12 (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) AUC 0-12 , 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 FEV 1 AUC 0-12 (mean difference 227 mls) and improved RV AUC 0-12 (mean difference - 558 mls) and R5-R20 AUC 0-12 (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 FEV 1 , 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://clinicaltrials.gov/ct2/show/NCT03842904 ).

Eur Respir J. 2005 Sep;26(3):511-22. (PMID: 16135736)
Am J Med. 2006 Oct;119(10 Suppl 1):21-31. (PMID: 16996896)
Eur Respir J. 2003 Dec;22(6):1026-41. (PMID: 14680096)
Am J Respir Crit Care Med. 2016 Sep 1;194(5):541-9. (PMID: 27585383)
Eur Respir J. 2019 May 18;53(5):. (PMID: 30846476)
Eur Respir J. 2005 Aug;26(2):319-38. (PMID: 16055882)
NPJ Prim Care Respir Med. 2016 Jun 16;26:16030. (PMID: 27309985)
BMC Pulm Med. 2013 Jun 03;13:35. (PMID: 23731868)
Lancet. 2016 Sep 3;388(10048):963-73. (PMID: 27598678)
Eur Respir J Suppl. 1993 Mar;16:5-40. (PMID: 8499054)
Eur Respir J. 2004 Jun;23(6):832-40. (PMID: 15218994)
Respir Res. 2015 Aug 02;16:92. (PMID: 26233481)
Int J Chron Obstruct Pulmon Dis. 2017 Jul 07;12:2001-2014. (PMID: 28744115)
N Engl J Med. 2008 Oct 9;359(15):1543-54. (PMID: 18836213)
Br J Clin Pharmacol. 2005 Apr;59(4):379-84. (PMID: 15801931)
N Engl J Med. 2004 Jun 24;350(26):2645-53. (PMID: 15215480)
Int J Chron Obstruct Pulmon Dis. 2017 Oct 06;12:2917-2928. (PMID: 29062229)
Br J Clin Pharmacol. 2015 May;79(5):695-708. (PMID: 25377687)
Br J Clin Pharmacol. 2015 Mar;79(3):492-500. (PMID: 25243340)
Eur Respir J. 2015 Mar;45(3):625-34. (PMID: 25359342)
Lancet. 2017 May 13;389(10082):1919-1929. (PMID: 28385353)
Br J Clin Pharmacol. 2008 Feb;65(2):244-52. (PMID: 18251761)
Int J Chron Obstruct Pulmon Dis. 2012;7:503-13. (PMID: 22973092)
Respir Res. 2019 Mar 4;20(1):49. (PMID: 30832670)
Respir Res. 2020 Sep 9;21(Suppl 1):102. (PMID: 32907566)
Curr Opin Pulm Med. 2020 Mar;26(2):162-168. (PMID: 31688242)
Int J Chron Obstruct Pulmon Dis. 2017 Jul 26;12:2179-2188. (PMID: 28794622)
Eur Respir J. 2012 Dec;40(6):1324-43. (PMID: 22743675)
Int J Chron Obstruct Pulmon Dis. 2017 May 22;12:1503-1506. (PMID: 28579768)
Lancet. 2018 Mar 17;391(10125):1076-1084. (PMID: 29429593)
Ther Adv Respir Dis. 2018 Jan-Dec;12:1753465818755091. (PMID: 29439648)
Eur Respir J. 2018 Apr 19;51(4):. (PMID: 29674480)

Keywords: COPD; Oscillometry; Small airways; Triple therapy

ClinicalTrials.gov NCT03842904

0 (Adrenergic beta-2 Receptor Agonists)
0 (Bronchodilator Agents)
0 (Drug Combinations)
0 (Glucocorticoids)
0 (Muscarinic Antagonists)
KGZ1SLC28Z (Beclomethasone)
V92SO9WP2I (Glycopyrrolate)
W34SHF8J2K (Formoterol Fumarate)

Date Created: 20201210 Date Completed: 20211007 Latest Revision: 20211007

20250114

PMC7727250

10.1186/s12931-020-01589-5

33298062