Stable chronic obstructive pulmonary disease in adult outpatients, focusing on exercise capacity/endurance assessed by constant-work-rate cycle testing. Respiratory
Conditions
Interventions
Interventional, randomised, open-label, four-period crossover trial: each participant receives four once-daily inhaled regimens in a balanced random order, each for 28 days with a 7-day washout betwee
2. Umeclidinium/vilanterol (Ellipta®): 55/22 µg, 1 inhalation once daily
3. Indacaterol/glycopyrronium (Breezhaler®): 110/54 µg, 1 capsule inhaled once daily
4. Tiotropium (Respimat®) — active control: 2 inhalations once daily (2.5 µg per actuation).
Randomisation: computer-generated balanced sequences (within-patient comparisons)
no masking. Short-acting bronchodilators permitted as rescue
inhaler technique checked at the start of each period.
Sponsors
Medical University of Bialystok
Eligibility
Sex/Gender
All
Age
40 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Adults aged 40 years and older 2. Stable chronic obstructive pulmonary disease (COPD), GOLD stage II–III, managed as outpatients 3. Smoking history of at least 10 pack-years 4. Post-bronchodilator FEV1/FVC ratio less than 0.70, measured by spirometry according to ATS/ERS standards 5. Post-bronchodilator FEV1 between 35% and 70% of predicted value 6. Clinically stable at enrolment, with no acute deterioration requiring a change in treatment 7. Able to perform cardiopulmonary exercise testing (CPET) on an electronically braked cycle ergometer, including both incremental and constant-work-rate tests at 80% W_peak 8. Willing and able to comply with all study procedures across four 28-day treatment periods and associated wash-out phases 9. Provided written informed consent prior to any study-related procedures
Exclusion criteria
Exclusion criteria: 1. Age less than 40 or greater than 75 years 2. Post-bronchodilator FEV1/FVC ratio equal to or greater than 0.70, which does not meet the COPD airflow-limitation criterion 3. Post-bronchodilator FEV1 less than 35% or greater than 70% of predicted, outside the target GOLD II–III range 4. Smoking history less than 10 pack-years 5. Recent COPD instability, including acute exacerbation, lower respiratory infection, or change in maintenance therapy within 4 weeks before screening 6. Frequent exacerbator phenotype, defined as two or more moderate or at least one severe exacerbation in the prior 12 months 7. Asthma or asthma–COPD overlap, including physician-diagnosed asthma or marked bronchodilator reversibility compatible with asthma (e.g. FEV1 increase of 400 mL or more and 15% or more) 8. Significant non-COPD lung disease, such as interstitial lung disease, clinically relevant bronchiectasis, active pulmonary tuberculosis, or untreated obstructive sleep apnoea with daytime instability 9. Active malignancy, except adequately treated non-melanoma skin cancer, or other uncontrolled systemic inflammatory or autoimmune disease 10. Unstable cardiovascular disease, including recent myocardial infarction within 6 months, unstable angina, decompensated heart failure, clinically significant arrhythmia, symptomatic severe valvular disease, or uncontrolled hypertension greater than 180/110 mmHg 11. Contraindications to exercise testing per ATS/ACCP guidelines, including conditions that make CPET unsafe such as acute pulmonary embolism or severe aortic stenosis 12. Resting hypoxaemia requiring unstable oxygen therapy or any condition that makes CPET unsafe in the investigator’s judgement 13. Neuromuscular, musculoskeletal, or neurological limitation that precludes safe cycling or completion of CPET or CWRCE 14. Pregnancy or breastfeeding, or women of childbearing potential not using effective contraception 15. Known hypersensitivity or intolerance to tiotropium, olodaterol, indacaterol, glycopyrronium, umeclidinium, vilanterol, or inhaler excipients 16. Use of prohibited medications or procedures, including investigational drugs within 30 days, chronic systemic corticosteroids over 10 mg prednisolone equivalent per day, initiation or change of LABA/LAMA/ICS within 4 weeks, or pulmonary rehabilitation started within 4 weeks prior to baseline 17. Severe uncontrolled comorbidity, such as end-stage renal or hepatic failure or uncontrolled thyroid disease, that could confound outcomes or increase risk 18. Inability to give informed consent or comply with study procedures due to cognitive impairment or substance misuse interfering with adherence
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cycling endurance time (seconds) measured using constant-work-rate cycle ergometry at 80% of baseline peak work during cardiopulmonary exercise testing (CPET; electronically braked cycle ergometer, breath-by-breath system—COSMED Quark CPET) at pre-treatment (Day 0) and post-treatment (Day 28) in each period; primary endpoint = change (post - pre) within period. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Dynamic hyperinflation (??IC) was measured using inspiratory capacity manoeuvres during constant-work-rate cycle ergometry (CWRCE) at 80% of baseline W_peak within CPET at Day 0 and Day 28 of each period. The summary metric was (IC_peak-IC_rest)_post - (IC_peak-IC_rest)_pre, with IC captured at rest, isotime, and peak. 2. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured using spirometry according to ATS/ERS standards at Day 0 and Day 28 of each period. 3. Ventilatory efficiency (VE/VCO2 at the ventilatory/lactate threshold) was measured using breath-by-breath CPET, with the threshold determined by V-slope and ventilatory equivalents at Day 0 and Day 28 of each period. 4. Peripheral oxygen saturation (SpO2) was measured using pulse oximetry during CPET at rest, isotime, and peak on Day 0 and Day 28 of each period. 5. Peak heart rate (HR_max) was measured using a 12-lead ECG signal within CPET at Day 0 and Day 28 of each period. 6. Peak oxygen uptake (VO2peak; in mL·min?¹ and mL·kg?¹·min?¹, % predicted) was measured using breath-by-breath CPET at Day 0 and Day 28 of each period. 7. Oxygen uptake at ventilatory/lactate threshold (VO2@VT1/LT1) was measured using CPET with VT1/LT1 determination at Day 0 and Day 28 of each period. 8. Oxygen pulse (VO2/HR at peak) was derived from CPET by dividing VO2peak by peak HR at Day 0 and Day 28 of each period. 9. Health status (SGRQ total score) and symptoms (CAT) were measured using validated questionnaires at Day 0 and Day 28 of each period. 10. Functional capacity (DASI, VSAQ) was measured using validated questionnaires at Day 0 and Day 28 of each period. 11. Dyspnoea was measured using the modified Medical Research Council scale (mMRC) at Day 0 and Day 28 of each period. 12. Plasma myostatin concentration was measured using enzyme-linked immunosorbent assay (ELISA) at Day 0 and Day 28 of each period. 13. Body composition indices including fat-free mass, fat mass, skeletal muscle mass, | — |
Countries
Poland
Contacts
Public ContactJakub Mroz
Outcome results
None listed