Comparative Effects of Triple Inhaled Therapy With Budesonide/Glycopyrronium/Formoterol Versus Fluticasone Furoate/Umeclidinium/Vilanterol on Small Airway Disease in COPD Patients: A Randomized Crossover Study

NCT06905483 | Completed Phase 4

• 1 other identifier: MTU-EC-IM-5-271/67
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to determine if triple inhaled therapy with Budesonide/Glycopyrronium/Formoterol (BGF) and Fluticasone Furoate/Umeclidinium/Vilanterol (FUV) are effective in treating patients with stable chronic obstructive pulmonary disease (COPD). It will also assess the safety of both drugs. The main questions it aims to answer are:

• Does BGF demonstrate a comparable effect to FUV in COPD participants?
• What medical problems do participants experience when taking BGFand FUV?

Conditions

Triple Therapy; Lung Function; COPD; Chronic Obstructive Pulmonary Disease (COPD); Small Airway Disease

Keywords

COPD; chronic obstructive pulmonary disease; small airway disease; triple inhaled therapy; Budesonide/Glycopyrronium/Formoterol; Fluticasone Furoate/Umeclidinium/Vilanterol

Outcome Measures

Primary Outcomes (4)

• Changes in airway resistance at 5 Hz (R5) on COPD patients

  Changes in R5 assessed by impulse oscillometry (IOS), reported as kPa/L/s and percent predicted value.

  From enrollment to the end of treatment at 8 weeks

• Changes in airway resistance at 20 Hz (R20) on COPD patients

  Changes in R20 assessed by impulse oscillometry (IOS), reported as kPa/L/s and percent predicted value.

  From enrollment to the end of treatment at 8 weeks

• Difference of airway resistance between 5 Hz and 20 Hz (R5-R20) on COPD patients

  Changes in R5-R20 assessed by impulse oscillometry (IOS), reported as kPa/L/s.

  From enrollment to the end of treatment at 8 weeks

• Reactance at 5 Hz (X5) on COPD patients

  Changes in X5 assessed by impulse oscillometry (IOS), reported as kPa/L/s.

  From enrollment to the end of treatment at 8 weeks

Secondary Outcomes (6)

• Changes in forced expiratory volume in 1 second (FEV1) in COPD patients

  From enrollment to the end of treatment at 8 weeks

• Changes in forced vital capacity (FVC) in COPD patients

  From enrollment to the end of treatment at 8 weeks

• Changes in FEV1/FVC ratio in COPD patients

  From enrollment to the end of treatment at 8 weeks

• Changes in forced expiratory flow at 25-75% of FVC (FEF25-75) in COPD patients

  From enrollment to the end of treatment at 8 weeks

• Changes in modified Medical Research Council dyspnea scale in COPD patients

  From enrollment to the end of treatment at 8 weeks

Study Arms (2)

Budesonide/Glycopyrronium/Formoterol (BGF)

EXPERIMENTAL

BGF (160/7.2/5 mcg) 2 inhalations, twice daily for 4 weeks

Drug: Budesonide/Glycopyrronium/Formoterol (BGF); Drug: Fluticasone Furoate/Umeclidinium/Vilanterol (FUV)

Fluticasone Furoate/Umeclidinium/Vilanterol (FUV)

ACTIVE COMPARATOR

FUV (100/62.5/25 mcg) 1 inhalation, once daily for 4 weeks

Drug: Budesonide/Glycopyrronium/Formoterol (BGF); Drug: Fluticasone Furoate/Umeclidinium/Vilanterol (FUV)

Interventions

Budesonide/Glycopyrronium/Formoterol (BGF) DRUG

Each patient received 4 weeks of treatment with either BGF or FUV followed by a 1-week washout period, and then 4 weeks of treatment with the other drug.

Also known as: Breztri

Budesonide/Glycopyrronium/Formoterol (BGF); Fluticasone Furoate/Umeclidinium/Vilanterol (FUV)

Fluticasone Furoate/Umeclidinium/Vilanterol (FUV) DRUG

Each patient received 4 weeks of treatment with either BGF or FUV followed by a 1-week washout period, and then 4 weeks of treatment with the other drug.

Also known as: Trelegy

Budesonide/Glycopyrronium/Formoterol (BGF); Fluticasone Furoate/Umeclidinium/Vilanterol (FUV)

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• COPD diagnosis confirmed by spirometry (post-bronchodilator FEV1/FVC \< 70%)
• Aged 40-80 years
• Smoking 10 pack-years or more
• Postbronchodilator FEV1 \< 80%

You may not qualify if:

• History of COPD exacerbation within 3 months
• Asthma, bronchiectasis, pulmonary fibrosis
• Inability to perform spirometry, impulse oscillometry, or 6-minute walk test
• Pregnant or breastfeeding women

Sponsors & Collaborators

• Thammasat University: lead

Study Sites (1)

Narongkorn Saiphoklang

Pathum Thani, Changwat Pathum Thani, 12120, Thailand

Location

Related Publications (17)

• Usmani O, Li G, De Backer J, Sadafi H, Wu L, Marshall J. Modeled small airways lung deposition of two fixed-dose triple therapy combinations assessed with in silico functional respiratory imaging. Respir Res. 2023 Sep 23;24(1):226. doi: 10.1186/s12931-023-02534-y.

  PMID: 37742015 RESULT

• Usmani OS, Scichilone N, Mignot B, Belmans D, Van Holsbeke C, De Backer J, De Maria R, Cuoghi E, Topole E, Georges G. Airway Deposition of Extrafine Inhaled Triple Therapy in Patients with COPD: A Model Approach Based on Functional Respiratory Imaging Computer Simulations. Int J Chron Obstruct Pulmon Dis. 2020 Oct 7;15:2433-2440. doi: 10.2147/COPD.S269001. eCollection 2020.

  PMID: 33116458 RESULT

• Bremner PR, Birk R, Brealey N, Ismaila AS, Zhu CQ, Lipson DA. Single-inhaler fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol plus umeclidinium using two inhalers for chronic obstructive pulmonary disease: a randomized non-inferiority study. Respir Res. 2018 Jan 25;19(1):19. doi: 10.1186/s12931-018-0724-0.

  PMID: 29370819 RESULT

• Bansal S, Anderson M, Anzueto A, Brown N, Compton C, Corbridge TC, Erb D, Harvey C, Kaisermann MC, Kaye M, Lipson DA, Martin N, Zhu CQ, Papi A. Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus tiotropium monotherapy in patients with COPD. NPJ Prim Care Respir Med. 2021 May 25;31(1):29. doi: 10.1038/s41533-021-00241-z.

  PMID: 34035312 RESULT

• Lipson DA, Barnacle H, Birk R, Brealey N, Locantore N, Lomas DA, Ludwig-Sengpiel A, Mohindra R, Tabberer M, Zhu CQ, Pascoe SJ. FULFIL Trial: Once-Daily Triple Therapy for Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2017 Aug 15;196(4):438-446. doi: 10.1164/rccm.201703-0449OC.

  PMID: 28375647 RESULT

• Maneechotesuwan K, Sawatdee S, Srichana T. In Vitro Analysis of Aerodynamic Properties and Co-Deposition of a Fixed-Dose Combination of Fluticasone Furoate, Umeclidinium Bromide, and Vilanterol Trifenatate. Pharmaceutics. 2024 Oct 18;16(10):1334. doi: 10.3390/pharmaceutics16101334.

  PMID: 39458663 RESULT

• Martinez FJ, Rabe KF, Ferguson GT, Wedzicha JA, Trivedi R, Jenkins M, Darken P, Aurivillius M, Dorinsky P. Benefits of budesonide/glycopyrrolate/formoterol fumarate (BGF) on symptoms and quality of life in patients with COPD in the ETHOS trial. Respir Med. 2021 Aug-Sep;185:106509. doi: 10.1016/j.rmed.2021.106509. Epub 2021 Jun 18.

  PMID: 34171789 RESULT

• Ishiura Y, Fujimura M, Ohkura N, Hara J, Kasahara K, Ishii N, Sawai Y, Shimizu T, Tamaki T, Nomura S. Triple Therapy with Budesonide/Glycopyrrolate/Formoterol Fumarate Improves Inspiratory Capacity in Patients with Asthma-Chronic Obstructive Pulmonary Disease Overlap. Int J Chron Obstruct Pulmon Dis. 2020 Feb 5;15:269-277. doi: 10.2147/COPD.S231004. eCollection 2020.

  PMID: 32103926 RESULT

• Rabe KF, Martinez FJ, Singh D, Trivedi R, Jenkins M, Darken P, Aurivillius M, Dorinsky P. Improvements in lung function with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler versus dual therapies in patients with COPD: a sub-study of the ETHOS trial. Ther Adv Respir Dis. 2021 Jan-Dec;15:17534666211034329. doi: 10.1177/17534666211034329.

  PMID: 34428980 RESULT

• Ferguson GT, Rabe KF, Martinez FJ, Fabbri LM, Wang C, Ichinose M, Bourne E, Ballal S, Darken P, DeAngelis K, Aurivillius M, Dorinsky P, Reisner C. Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomised controlled trial. Lancet Respir Med. 2018 Oct;6(10):747-758. doi: 10.1016/S2213-2600(18)30327-8. Epub 2018 Sep 16.

  PMID: 30232048 RESULT

• Usmani O, Roche N, Wahab E, Israel S, Jenkins M, Trivedi R, Dorinsky P, Aurivillius M. A scintigraphy study of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler in patients with moderate-to-very severe chronic obstructive pulmonary disease. Respir Res. 2021 Oct 7;22(1):261. doi: 10.1186/s12931-021-01813-w.

  PMID: 34620167 RESULT

• Bickel S, Popler J, Lesnick B, Eid N. Impulse oscillometry: interpretation and practical applications. Chest. 2014 Sep;146(3):841-847. doi: 10.1378/chest.13-1875.

  PMID: 25180727 RESULT

• McNulty W, Usmani OS. Techniques of assessing small airways dysfunction. Eur Clin Respir J. 2014 Oct 17;1. doi: 10.3402/ecrj.v1.25898. eCollection 2014.

  PMID: 26557240 RESULT

• Lazarinis N, Fouka E, Linden A, Bossios A. Small airways disease in chronic obstructive pulmonary disease. Expert Rev Respir Med. 2024 Jul;18(7):539-552. doi: 10.1080/17476348.2024.2380070. Epub 2024 Jul 24.

  PMID: 39046133 RESULT

• Singh D, Long G, Cancado JED, Higham A. Small airway disease in chronic obstructive pulmonary disease: insights and implications for the clinician. Curr Opin Pulm Med. 2020 Mar;26(2):162-168. doi: 10.1097/MCP.0000000000000637.

  PMID: 31688242 RESULT

• Verleden SE, Hendriks JMH, Snoeckx A, Mai C, Mentens Y, Callebaut W, De Belie B, Van Schil PE, Verplancke V, Janssens A, Jacob J, Pakzad A, Conlon TM, Guvenc G, Yildirim AO, Pauwels P, Koljenovic S, Kwakkel-Van Erp JM, Lapperre TS. Small Airway Disease in Pre-Chronic Obstructive Pulmonary Disease with Emphysema: A Cross-Sectional Study. Am J Respir Crit Care Med. 2024 Mar 15;209(6):683-692. doi: 10.1164/rccm.202301-0132OC.

  PMID: 38055196 RESULT

• Sudi A, Santa B, Horvath A, Tomisa G, Abonyi-Toth Z, Rokszin G, Eszes N, Muller V, Tamasi L. The Real-World Efficacy of Fixed Triple Inhalation Therapy in the Treatment of Moderate COPD Patients (RATIONALE Study). Int J Chron Obstruct Pulmon Dis. 2024 Aug 28;19:1943-1955. doi: 10.2147/COPD.S474354. eCollection 2024.

  PMID: 39219564 RESULT

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Budesonide; fluticasone furoate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Narongkorn Saiphoklang, MD

  Thammasat University Faculty of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: This study is a randomized crossover study. COPD patients aged 40 years or older with stable disease are included. Each patient receives four weeks of treatment with either BGF or FUV followed by a one-week washout period, and then four weeks of treatment with the other drug. Respiratory symptoms, pulmonary function, and safety are assessed.

Study Record Dates

• First Submitted: March 22, 2025
• First Posted: April 1, 2025
• Study Start: April 1, 2025
• Primary Completion: December 31, 2025
• Study Completion: January 28, 2026
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: IPD and documents will be available for sharing immediately after publication for a period of 2 years.
• Access Criteria: All researchers will be able to access the IPD and supporting information via the repository website without restriction.

Locations

TH (1)