Comparative Efficacy of Once-daily LAMA/LABA Combinations Versus Tiotropium on Constant-work-rate Cycle Endurance in COPD: Randomised Crossover Study (COMPETE)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Suspended
- Sponsor
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Endurance time during constant-work-rate cycle ergometry (CWRCE)
Study Overview
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.
Detailed Description
Rationale and Objectives Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation, exertional dyspnea, and exercise intolerance, with dynamic and static hyperinflation as key physiological determinants of symptoms and functional limitation. Long-acting bronchodilators are a cornerstone of COPD management. Fixed-dose combinations of a long-acting β2-agonist with an ultra-long-acting muscarinic antagonist (LABA/uLAMA) may reduce hyperinflation more effectively than LAMA monotherapy, but direct, head-to-head evidence across the marketed combinations remains limited, particularly with objective exercise endpoints.
Primary objective: to compare the effect of marketed LABA/uLAMA combinations versus tiotropium (LAMA) on exercise capacity in patients with COPD.
Key secondary aim: to compare pharmacoeconomic efficiency (cost and cost-effectiveness metrics) among these therapies.
Design Overview Prospective, randomized, open-label, four-period crossover (head-to-head) study conducted at a single academic center. Each treatment period lasts 28 days, separated by a 7-day wash-out. Every participant receives each study treatment according to a randomized sequence. The crossover design allows within-patient comparisons that limit between-subject variability. (Enrollment numbers, dates, allocation, and arm details are provided in the structured fields.)
Setting and Eligibility Single-center study at the 2nd Department of Pulmonology and Tuberculosis, Medical University of Białystok, and the affiliated University Hospital Pulmonology Outpatient Clinic. Adults with a confirmed diagnosis of COPD were eligible per protocol-specified spirometric criteria and clinical stability. Key exclusions included major cardiovascular instability (e.g., recent myocardial infarction, unstable angina, uncontrolled arrhythmia), critical valvular disease, acute inflammatory or metabolic conditions that would confound exercise testing, inability to safely perform exercise testing, and conditions precluding informed cooperation. (Complete inclusion/exclusion lists are captured in the Eligibility section.)
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Single (Investigator)
Eligibility Criteria
- Ages
- 30 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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
- •Physical disability preventing safe and adequate CPET performance
- •Cognitive impairment precluding cooperation
Arms & Interventions
Tiotropium (LAMA)
Participants receive tiotropium 2.5 μg per actuation, 2 inhalations once daily (Spiriva Respimat®) for 28 days.
Intervention: Tiotropium (Drug)
Tiotropium/Olodaterol (LAMA/LABA)
Participants receive tiotropium 2.5 μg + olodaterol 2.5 μg per actuation, 2 inhalations once daily (Spiolto Respimat®) for 28 days.
Intervention: Tiotropium (Drug)
Tiotropium/Olodaterol (LAMA/LABA)
Participants receive tiotropium 2.5 μg + olodaterol 2.5 μg per actuation, 2 inhalations once daily (Spiolto Respimat®) for 28 days.
Intervention: Olodaterol (Drug)
Umeclidinium/Vilanterol (LAMA/LABA)
Participants receive umeclidinium 55 μg + vilanterol 22 μg, 1 inhalation once daily (Anoro Ellipta®) for 28 days.
Intervention: Umeclidinium (Drug)
Umeclidinium/Vilanterol (LAMA/LABA)
Participants receive umeclidinium 55 μg + vilanterol 22 μg, 1 inhalation once daily (Anoro Ellipta®) for 28 days.
Intervention: Vilanterol (Drug)
Indacaterol/Glycopyrronium (LABA/LAMA)
Participants receive indacaterol 110 μg + glycopyrronium 54 μg, 1 capsule inhaled once daily (Ultibro Breezhaler®) for 28 days.
Intervention: Indacaterol (Drug)
Indacaterol/Glycopyrronium (LABA/LAMA)
Participants receive indacaterol 110 μg + glycopyrronium 54 μg, 1 capsule inhaled once daily (Ultibro Breezhaler®) for 28 days.
Intervention: Glycopyrronium (Drug)
Outcomes
Primary Outcomes
Endurance time during constant-work-rate cycle ergometry (CWRCE)
Time Frame: Baseline and after 28 days of each treatment period
Change in endurance time (ET) during constant-work-rate exercise testing at 80% peak workload, measured by cardiopulmonary exercise testing (CPET).
Secondary Outcomes
- 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)
- Inspiratory capacity at isotime during CPET(Baseline and after 28 days of each treatment period)
- Inspiratory capacity at peak exercise during CPET(Baseline and after 28 days of each treatment period)
- St. George's Respiratory Questionnaire (SGRQ) total score(Baseline and after 28 days of each treatment period)
- Dyspnoea intensity at isotime measured by the Modified Borg Dyspnoea Scale(Baseline and after 28 days of each treatment period)
- COPD Assessment Test (CAT) total score(Baseline and after 28 days of each treatment period)
- Veterans Specific Activity Questionnaire (VSAQ) score(Baseline and after 28 days of each treatment period)
- Duke Activity Status Index (DASI) total score(Baseline and after 28 days of each treatment period)
- Dyspnoea intensity at peak exercise measured by the Modified Borg Dyspnoea Scale(Baseline and after 28 days of each treatment period)
- Modified Medical Research Council (mMRC) Dyspnoea Scale score(Baseline and after 28 days of each treatment period)