Comparative Efficacy of Once-daily LAMA/LABA Combinations Versus Tiotropium on Constant-work-rate Cycle Endurance in COPD

NCT07541378 | Suspended

• 1 other identifier: APK.002.200.300.2022
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to directly compare the effects of widely available long-acting bronchodilator therapies in patients with chronic obstructive pulmonary disease (COPD). The trial evaluates three fixed-dose combinations of a long-acting beta-2 agonist and a long-acting muscarinic antagonist (LABA/uLAMA)-umeclidinium/vilanterol (Anoro® Ellipta), indacaterol/glycopyrronium (Ultibro® Breezhaler), and tiotropium/olodaterol (Spiolto® Respimat)-against tiotropium (Spiriva®), a long-acting muscarinic antagonist (LAMA) used as monotherapy. The primary aim is to assess their impact on exercise capacity, with additional evaluation of pharmacoeconomic outcomes. The study follows a prospective, randomized, open-label, four-period crossover design. Approximately 100 patients with stable COPD will be enrolled from the 2nd Department of Pulmonology and Tuberculosis, Medical University of Białystok, and the University Hospital Pulmonology Outpatient Clinic. Each treatment will last 28 days, separated by a 7-day wash-out period, so that every participant will receive each therapy. Assessments will include standard clinical examinations, lung function testing (spirometry, body plethysmography, DLCO, multiple-breath washout), cardiopulmonary exercise testing (CPET) on a cycle ergometer, the 6-minute walk test, validated questionnaires (SGRQ, CAT, mMRC, BODE index), laboratory tests, and imaging. These procedures are part of routine COPD evaluation and will allow detailed monitoring of respiratory function, exercise tolerance, and quality of life. The study aims to determine whether dual bronchodilation with LABA/uLAMA combinations provides superior improvements in exercise performance and overall efficiency compared to tiotropium alone. Results may help guide clinical decision-making and optimize cost-effectiveness in COPD management.

Conditions

COPD (Chronic Obstructive Pulmonary Disease)

Keywords

copd; cpet; bronchodilators; laba; lama; Chronic Obstructive Pulmonary Disease; Pulmonary Disease Chronic Obstructive; LABA/LAMA; uLAMA; cardiopulmonary exercise testing; exercise capacity

Outcome Measures

Primary Outcomes (1)

• Endurance time during constant-work-rate cycle ergometry (CWRCE)

  Change in endurance time (ET) during constant-work-rate exercise testing at 80% peak workload, measured by cardiopulmonary exercise testing (CPET).

  Baseline and after 28 days of each treatment period

Secondary Outcomes (14)

• Peak oxygen uptake (VO₂peak) during CPET

  Baseline and after 28 days of each treatment period

• Oxygen uptake (VO₂) at isotime during CPET

  Baseline and after 28 days of each treatment period

• Forced expiratory volume in 1 second (FEV₁)

  Baseline and after 28 days of each treatment period

• Forced vital capacity (FVC)

  Baseline and after 28 days of each treatment period

• Inspiratory capacity at rest during CPET

  Baseline and after 28 days of each treatment period

Other Outcomes (5)

• Plasma myostatin concentration

  Baseline V1 and after each 28-day treatment period

• Body fat percentage assessed by bioelectrical impedance analysis

  Baseline V1 and after 28 days of each treatment period

• Fat-free mass assessed by bioelectrical impedance analysis

  Baseline V1 and after 28 days of each treatment period

Study Arms (4)

Tiotropium (LAMA)

ACTIVE COMPARATOR

Participants receive tiotropium 2.5 μg per actuation, 2 inhalations once daily (Spiriva Respimat®) for 28 days.

Drug: Tiotropium

Tiotropium/Olodaterol (LAMA/LABA)

EXPERIMENTAL

Participants receive tiotropium 2.5 μg + olodaterol 2.5 μg per actuation, 2 inhalations once daily (Spiolto Respimat®) for 28 days.

Drug: Tiotropium; Drug: Olodaterol

Umeclidinium/Vilanterol (LAMA/LABA)

EXPERIMENTAL

Participants receive umeclidinium 55 μg + vilanterol 22 μg, 1 inhalation once daily (Anoro Ellipta®) for 28 days.

Drug: Umeclidinium; Drug: Vilanterol

Indacaterol/Glycopyrronium (LABA/LAMA)

EXPERIMENTAL

Participants receive indacaterol 110 μg + glycopyrronium 54 μg, 1 capsule inhaled once daily (Ultibro Breezhaler®) for 28 days.

Drug: Indacaterol; Drug: Glycopyrronium

Interventions

Tiotropium DRUG

Tiotropium bromide, long-acting muscarinic antagonist (LAMA). Administered as 2.5 μg per actuation, 2 inhalations once daily via Respimat inhaler for 28 days.

Also known as: Spiriva Respimat, Spiriva

Tiotropium (LAMA); Tiotropium/Olodaterol (LAMA/LABA)

Olodaterol DRUG

Olodaterol, long-acting beta2-agonist (LABA). Administered as 2.5 μg per actuation, 2 inhalations once daily via Respimat inhaler for 28 days in combination with tiotropium.

Tiotropium/Olodaterol (LAMA/LABA)

Umeclidinium DRUG

Umeclidinium bromide, long-acting muscarinic antagonist (LAMA). Administered as 55 μg, 1 inhalation once daily via Ellipta inhaler for 28 days in combination with vilanterol.

Umeclidinium/Vilanterol (LAMA/LABA)

Vilanterol DRUG

Vilanterol, long-acting beta2-agonist (LABA). Administered as 22 μg, 1 inhalation once daily via Ellipta inhaler for 28 days in combination with umeclidinium.

Umeclidinium/Vilanterol (LAMA/LABA)

Indacaterol DRUG

Indacaterol maleate, long-acting beta2-agonist (LABA). Administered as 110 μg, 1 capsule inhaled once daily via Breezhaler device for 28 days in combination with glycopyrronium.

Indacaterol/Glycopyrronium (LABA/LAMA)

Glycopyrronium DRUG

Glycopyrronium bromide, long-acting muscarinic antagonist (LAMA). Administered as 54 μg, 1 capsule inhaled once daily via Breezhaler device for 28 days in combination with indacaterol.

Indacaterol/Glycopyrronium (LABA/LAMA)

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent for study participation
• Diagnosis of COPD
• Age ≥30 years and ≤70 years
• Post-bronchodilator FEV₁ ≤80% and ≥30% predicted
• BMI ≥15 kg/m² and \<40 kg/m²

You may not qualify if:

• Lack of informed consent for study participation
• No confirmed diagnosis of COPD
• Age \<30 years or \>70 years
• FEV₁ \>80% or \<30% predicted
• BMI \<15 kg/m² or ≥40 kg/m²
• Inability to self-care or lack of long-term family or caregiver support
• Recent myocardial infarction (within 3 months before enrollment)
• Unstable angina
• Uncontrolled arrhythmias detected on ECG at screening or immediately before CPET
• Critical aortic stenosis at screening
• Acute myocarditis or pericarditis
• Acute cardiovascular conditions such as pulmonary embolism, aortic dissection, or endocarditis
• Acute systemic conditions that may interfere with exercise testing or worsen under stress (e.g., infections, renal failure, thyrotoxicosis)
• Deep vein thrombosis
• Uncontrolled asthma

Sponsors & Collaborators

• Medical University of Bialystok: lead

Study Sites (1)

II Department of Lung Diseases, Lung Cancer and Internal Diseases

Bialystok, Podlaskie Voivodeship, 15-540, Poland

Location

Related Publications (5)

• Mejza F.: Postępowanie w przewlekłej obturacyjnej chorobie płuc. Podsumowanie wytycznych Global Initiative for Obstructive Lung Disease (GOLD) 2020. Med. Prakt., 2020; 2: 38-50

  RESULT

• 5. Koarai, A., Sugiura, H., Yamada, M. et al. Treatment with LABA versus LAMA for stable COPD: a systematic review and meta-analysis. BMC Pulm Med 20, 111 (2020). https://doi.org/10.1186/s12890-020-1152-8

  RESULT

• A. Bourdin, P-R Burgel, P. Chanez, G. Garcia, T. Perez, N. Roche Recent advances in COPD: pathophysiology, respiratory physiology and clinical aspects, including comorbiditiesEuropean Respiratory Review Dec 2009, 18 (114) 198-212;

  RESULT

• Bill B Brashier , Rahul Kodgule, Risk Factors and Pathophysiology of Chronic Obstructive Pulmonary Disease (COPD), The Journal of the Association of Physicians of India, 2012

  RESULT

• 1. World Health Organization. Chronic Obstructive Pulmonary Disease. Key Facts https://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease- (copd)

  RESULT

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Tiotropium Bromide; olodaterol; GSK573719; vilanterol; indacaterol; Glycopyrrolate

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)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Quaternary Ammonium Compounds; Amines; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Robert M Mroz, professor

  Medical University of Bialystok

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, randomized, open-label, four-period crossover (head-to-head) study conducted at a single academic center.

Study Record Dates

• First Submitted: April 7, 2026
• First Posted: April 21, 2026
• Study Start: March 11, 2024
• Primary Completion: February 7, 2025
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 21, 2026

Record last verified: 2026-04

Locations

PL (1)