Can commonly used treatment with inhaled corticosteroids protect COPD patients from heart and blood vessel disease?
| ISRCTN | ISRCTN11747857 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11747857 |
| Integrated Research Application System (IRAS) | 1010334 |
| Protocol serial number | 173960 |
| Sponsor | Imperial College London |
| Funder | AstraZeneca UK |
- Submission date
- 26/09/2024
- Registration date
- 04/10/2024
- Last edited
- 27/07/2026
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Respiratory
Plain English summary of protocol
Background and study aims
Chronic obstructive pulmonary disease (COPD) is a common lung disease, mainly caused by smoking. Heart disease is a leading cause of death in COPD patients, but the connection between the two conditions isn't fully clear. Standard treatment for COPD includes inhalers with two bronchodilators, called long-acting muscarinic receptor antagonists (LAMAs) and long-acting β2 agonists (LABAs). For severe COPD or frequent flare-ups, a combination of bronchodilators and inhaled corticosteroids (ICS) is recommended (ICS/LAMA/LABA triple therapy), as it reduces flare-ups and improves survival rates.
The cells lining blood vessels, called endothelial cells, are key for heart and blood vessel health. When these cells age, blood vessels don't work well, leading to heart disease. Studies show that blood cells from COPD patients, which should turn into endothelial cells and repair damage, are dysfunctional and age prematurely. Interestingly, patients treated with both bronchodilators and ICS had healthier endothelial cells than those treated with bronchodilators alone.
This study aims to understand why blood vessels age prematurely in COPD and how ICS treatment may protect patients from heart disease.
Who can participate?
COPD patients aged 18 years and over who have not previously used ICS.
What does the study involve?
Participants will attend the research facility for 2–3 visits. During the first visit (the "screening visit"), we will ask about medical history, do a lung function test, and have participants fill out a questionnaire on their COPD symptoms. Participants will also provide consent to join the study. This visit will include:
1. Lung function test (spirometry)
2. A simple exercise test
3. Questionnaires about breathing symptoms
4. Blood pressure, height, and weight measurements
5. A non-invasive test to assess blood vessel health
6. A blood sample collection
If participants wish, the screening and study visits can be combined into one, lasting less than 4 hours. However, if participants are not suitable after screening, they will not proceed to the main study.
After the first visit, participants will collect their medication from the Royal Brompton Hospital pharmacy. They will then return for a second visit 12 weeks later, where the same tests will be repeated.
Participants will be split into two groups: one group will receive bronchodilators (LABA/LAMA) only, and the other will receive ICS/LAMA/LABA triple therapy for 12 weeks. The study will measure blood vessel function and stiffness and ageing of endothelial cells before and after treatment to determine whether ICS can prevent premature blood vessel ageing and reduce heart disease in COPD patients.
What are the possible benefits and risks of participating?
The procedures in this study are not expected to cause harm. The only risk from the blood test is slight discomfort or bruising, as 80ml of blood (about 4-5 tablespoons) will be taken. Some people (less than 5%) may feel faint, but the amount of blood taken is small and won't have long-lasting effects. The clinical procedures are non-invasive, though the blood pressure cuff used to measure blood vessel health may cause brief discomfort. If it’s not tolerated, the cuff will be deflated.
The inhalers used in the study are commonly prescribed to COPD patients and are usually well tolerated. Participants will be informed of any possible side effects and given instructions on where to seek help if needed.
Where Is the study run from?
Imperial College London (UK)
When is the study starting and how long is it expected to run for?
August 2024 to May 2026
Who is funding the study?
AstraZeneca (UK)
Who is the main contact?
Dr Koralia Paschalaki k.paschalaki@imperial.ac.uk
Contact information
Public, Scientific, Principal investigator
Imperial College London 5th Floor
ICTEM building
Hammersmith Campus
London
W12 0NN
United Kingdom
| Phone | +44 (0)20 7594 2728 |
|---|---|
| k.paschalaki@imperial.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Single-blind randomized controlled trial |
| Secondary study design | Randomised controlled trial |
| Participant information sheet | 46132_PIS.pdf |
| Scientific title | Understanding the role of inhaled corticosteroids on vascular ageing and cardiovascular comorbidities in COPD |
| Study objectives | Do inhaled corticosteroids (ICS) reduce endothelial ageing, protecting COPD patients from vascular ageing and cardiovascular events? 1. To correlate molecular with clinical information of endothelial dysfunction 2. To identify molecular abnormalities that promote vascular ageing and novel therapeutic opportunities to restore endothelial dysfunction 3. To study the effect of various drugs against accelerated ageing of endothelial cells isolated from patients’ blood samples in the laboratory 4. To confirm the protective effect of ICS/triple combination on endothelial senescence ex vivo using ECFC (2D and 3D culture models) |
| Ethics approval(s) |
Approved 03/10/2024, Wales Research Ethics Committee 3 (Health and Care Research Wales, Castlebridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, United Kingdom; -; Wales.REC3@wales.nhs.uk), ref: 24/WA/0260 |
| Health condition(s) or problem(s) studied | Chronic obstructive pulmonary disease (COPD) |
| Intervention | Intervention arm: Patients randomised to the intervention arm will receive Trixeo Aerosphere (formoterol fumarate/glycopyrronium/budesonide - 5 micrograms/7.2 micrograms/160 micrograms pressurised inhalation, suspension). They will be instructed to take two inhalations twice daily (two in the AM and two in the PM). The treatment duration is 12 weeks. Control arm: Patients randomised to the intervention arm will receive Bevespi Aerosphere (formoterol fumarate/glycopyrronium 5 micrograms / 7.2 micrograms pressurised inhalation, suspension). They will be instructed to take two inhalations twice daily (two in the AM and two in the PM). The treatment duration is 12 weeks. Follow-up activities: Both groups will receive a telephone call from the trial team at 4 and 8 weeks of the treatment period to reinforce compliance and collect information about adverse events. Once the 12-week treatment period has been completed, patients will attend the clinical research facility to repeat the outcome measures performed at baseline. Randomisation: Randomisation will be conducted using sealed envelope, patients will be randomised on a 1:1 ratio stratified by age and gender. The randomisation will occur at the end of visit 1, the trial pharmacist will be unblinded and dispense the medication according to group allocation. |
| Intervention type | Drug |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Trixeo (formoterol fumarate dihydrate - approved, glycopyrronium bromide, budesonide), Bevespi (formoterol fumarate dihydrate - approved, glycopyrronium bromide) |
| Primary outcome measure(s) |
Degree of senescence in endothelial progenitors isolated from blood (endothelial colony forming cells: ECFC), measured by markers of senescence and DNA damage response, isolated from COPD patients at baseline and 12 weeks post-treatment |
| Key secondary outcome measure(s) |
Measured at baseline and 12 weeks post-treatment: |
| Completion date | 31/05/2026 |
| Reason abandoned (if study stopped) | Lack of staff/facilities/resources |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 110 Years |
| Sex | All |
| Target sample size at registration | 60 |
| Total final enrolment | 4 |
| Key inclusion criteria | 1. Clinical diagnosis of COPD 2. Not on regular treatment with inhaled corticosteroids (ICS) 3. Over 18 years of age 4. Symptomatic disease (COPD Assessment Test [CAT] score of ≥10) 5. FEV1 measured by spirometry <80% predicted 6. Able to demonstrate adequate inhaler technique 7. Willing to take study medications as instructed |
| Key exclusion criteria | 1. Subjects unable to give informed consent form 2. Pregnancy or breastfeeding 3. Patients on regular treatment with inhaled corticosteroids (ICS) 4. Very severe disease FEV1<30% 5. Patients with more than two moderate exacerbations, or one severe (requiring hospitalization) within the last year 6. Patients with significant cardiac comorbidities, arrhythmias and/or on antiplatelet treatment 7. Patients with acute worsening of COPD in the 6 weeks prior to screening resulting in treatment with oral corticosteroids or antibiotics 8. Patients with asthma, other significant comorbidities including cancer, neurological, hepatic, endocrine, renal (creatinine clearance <30 ml/min) disorders, narrow-angle glaucoma or prostatic hypertrophy 9. Patients who are taking part in interventional clinical trials 10. Patients with known hypersensitivity to budesonide, glycopyrronium or formoterol 11. For women of childbearing potential only – currently pregnant, breastfeeding, or planned pregnancy during the study or not using acceptable contraception, as judged by the investigator 12. Patients with allergy to latex 13. As a result of the medical interview, physical examination or screening investigations, the Physician Responsible considers the volunteer unfit for the study |
| Date of first enrolment | 26/02/2025 |
| Date of final enrolment | 05/03/2026 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centres
Fulham Road Wing
Dovehouse Street
London
SW3 6JY
England
St Marys Hospital
South Wharf Road
London
W2 1BL
England
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request from the primary investigator (Koralia Paschalaki k.pachalaki@imperial.ac.uk). The data that will be shared will be anonymised trial outcome data, for further scientific analysis or systematic reviews/meta-analyses. The primary investigator will assess any requests for data sharing, only data that patients have consented to be shared (upon entry into the trial) will be made available. Data sharing will be conducted electronically via password-protected datasets. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | 04/10/2024 | No | Yes | ||
| Protocol file | version 1.1 | 01/10/2024 | 04/10/2024 | No | No |
Additional files
- 46132_PIS.pdf
- Participant information sheet
- 46132_PROTOCOL.pdf
- Protocol file
Editorial Notes
27/07/2026: The study was terminated early on 05/03/2026 due to operational and feasibility issues. The study is being terminated early for operational and feasibility reasons and not due to any safety concerns, unexpected adverse events, or changes in the risk-benefit profile of the investigational medicinal product.
This investigator-initiated Phase IV mechanistic study was designed to investigate the effects of inhaled corticosteroid-based therapy on vascular and cardiovascular mechanisms in patients with COPD. The study involved recruitment of a highly specific participant population and complex specialised laboratory analyses. Although recruitment pathways were expanded and eligible participants were identified, recruitment progressed more slowly than anticipated and over a longer timeframe than originally planned. At the time of termination, 4 participants had been recruited, compared with a planned sample size of 60 participants.
The ability to continue the study was further affected by operational challenges, including changes in research staffing and limited capacity to support the specialised clinical and laboratory activities required for study delivery. As a result, the study objectives could not be achieved within the available funding period and operational timelines.
Following discussion between the Sponsor/Institution and the funder (AstraZeneca), it was concluded that continuation of the study was no longer feasible. Early termination has therefore been undertaken to allow appropriate study closure, including completion of regulatory requirements, data reconciliation, archiving, and final reporting in accordance with Sponsor and regulatory requirements.
The decision to terminate the study does not affect the scientific rationale underpinning the research question. Related research in this therapeutic area continues through ongoing AstraZeneca-sponsored clinical development programmes, and future investigation of the study objectives may be considered should appropriate opportunities and resources become available.
22/10/2025: The study participating centres were updated. The date of final enrolment was changed from 30/10/2025 to 30/01/2026.
06/03/2025: The recruitment start date was changed from 05/02/2025 to 26/02/2025.
28/01/2025: The recruitment start date was changed from 28/01/2025 to 05/02/2025.
20/11/2024: Ethics approval details added. The recruitment start date was changed from 06/11/2024 to 28/01/2025.
26/09/2024: Study's existence confirmed by the HRA.
