Treatment with medications that prevent the formation of blood clots, in the primary prevention of heart disease in patients with a stable lung condition called Chronic Obstructive Pulmonary Disease (COPD)
| ISRCTN | ISRCTN43245574 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN43245574 |
| EudraCT/CTIS number | 2014-005475-86 |
| Secondary identifying numbers | CPMS 19244 |
- Submission date
- 21/10/2015
- Registration date
- 21/10/2015
- Last edited
- 08/11/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English Summary
Background and study aims
Chronic obstructive pulmonary disease (COPD) is the collective name for a group of diseases which affect the lungs. People who suffer from COPD have difficulty breathing, which gets worse over time. This is because the airways become narrowed or blocked, and the air sacs (alveoli) in the lungs are destroyed or lose their ability to stretch. The main cause of COPD is smoking, which over time permanently damages the lining of the lungs. Many studies have shown that people with COPD have a greater risk of developing heart and blood vessel disease (cardiovascular disease) which can lead to a heart attack. When a person is suffering from cardiovascular disease (CVD), fatty substances (plaque) build up inside blood vessels causing them to become narrowed. Platelets (a component of blood) “stick” to the walls of these narrowed blood vessels, causing blockages (occlusion) that can lead to a heart attack. Ticagrelor is a medication which works by slowing and stopping platelets from sticking to the blood vessel walls. It is usually taken with aspirin, which makes this more effective by “thinning” the blood. These medications are often used in CVD patients and have been shown to be very effective. Currently there is very little information about the best way to treat COPD patients who are at risk of heart disease. The aim of this study is to find out whether treatment with ticagrelor and/or aspirin can help to lower the risk of heart disease in COPD patients.
Who can participate?
Adults who have smoked for at least 10 years with signs of COPD.
What does the study involve?
Participants are randomly allocated to one of three treatment groups or a control group. Those in the treatment groups are given aspirin and/or ticagrelor to take, and those in the control group are given a placebo (dummy pill). At the initial visit, participants will undergo a blood test, a lung function test, an ultrasound scan, they will have their stiffness of the blood vessels measured and they will be asked to complete questionnaires. Participants who are receiving the treatment attend follow up visits at 1, 3 and 6 months to see whether the medication is having any effect. The blood tests and questionnaires are repeated at a 6 month follow up visit for both groups.
What are the possible benefits and risks of participating?
There are no direct benefits to the patient for participating in this study. However, their participation in this study may add to the medical knowledge about how to treat COPD patients who are at risk of future heart problems. There are minor risks related to taking the study medications (asprin and ticagrelor), however the benefits have been judged to outweigh the risks.
Where is the study run from?
Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
September 2015 to November 2017
Who is funding the study?
AstraZeneca UK Limited (UK)
Who is the main contact?
Catherine Brennand
cath.brennand@ncl.ac.uk
Contact information
Public
Newcastle Clinical Trials Unit
Faculty of Medical Sciences
1-4 Claremont Terrace
Newcastle University
Newcastle Upon Tyne
NE2 4AE
United Kingdom
| Phone | +44 (0)191 208 7258 |
|---|---|
| cath.brennand@ncl.ac.uk |
Study information
| Study design | Randomized; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Anti-platelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease |
| Study acronym | APPLE-COPD:ICON 2 |
| Study hypothesis | The aim of this study is to find out whether ticagrelor and/or aspirin are effective treatments in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease. |
| Ethics approval(s) | First Medical Research Ethics Commitee, 26/05/2015, ref: 15/NE/0155 |
| Condition | Topic: Cardiovascular disease, Respiratory disorders; Subtopic: Cardiovascular (all Subtopics), Respiratory (all Subtopics); Disease: Cardiovascular, Respiratory |
| Intervention | Patients who meet the inclusion criteria with a QRISK2 score >20% will be randomised to the treatment arm. A stratified blocked treatment allocation system is used to randomise patients into four groups who each receive a different treatment for six months: 1. Aspirin (75 mg once daily dose) and Ticagrelor (90 mg twice daily dose) 2. Aspirin (75 mg once daily dose) and placebo 3. Ticagrelor (90 mg twice daily dose) and placebo 4. Placebo alone Block size will not be disclosed to the investigators. Randomisation will be administered centrally via the Newcastle Clinical Trials Unit using a secure web-based system. Patients will attend follow-up visits at the Clinical Research Facility, Royal Victoria Infirmary at 1-month, 3-months and 6-months and then followed up clinically for up to 1 year. Patients with a QRISK2 score <20% will be allocated to the observational cohort of the study, they will undergo the baseline procedures, including blood tests and will be followed up again at 1 year. Patients in the observational cohort will not undergo follow-up visits at 1 month, 3 months and 6 months. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Aspirin, ticagrelor |
| Primary outcome measure | Inhibition of adenosine disphosphate-induced platelet aggregation measured using the multiplate test at baseline and 6 months. |
| Secondary outcome measures | 1. Changes in inflammatory markers including fibrinogen, hsCRP, TNF alpha, IL-6, MPO is measured from blood samples taken at baseline and 6 months 2. Changes in carotid intima media thickness measured using an ultrasound probe and vascular stiffness measured using a specialised pressure cuff similar to a blood pressure cuff at baseline and 6 months 3. Quality of life measured using questionnaires (EQ5D-5L, St. George’s COPD questionnaire) at baseline and 6 months |
| Overall study start date | 04/09/2015 |
| Overall study end date | 10/11/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 240; UK Sample Size: 240; Description: Interventional arm - 120 Observational arm - 120 |
| Total final enrolment | 120 |
| Participant inclusion criteria | 1. Aged 18 years or over 2. Abnormal spirometry with FEV1<80% and FEV1/FVC ratio <70% of predicted 3. Smoking history that is 10 years or greater (current or ex smokers can be included) 4. Patient has the capacity to consent |
| Participant exclusion criteria | 1. Any condition that is being concurrently treated through anticoagulation or antiplatelet therapy (atrial fibrillation, deep vein thrombosis, valve prosthesis, recent myocardial infarction, use of drug eluting stents) 2. Other specific contraindications to management with antiplatelet medication (bleeding risks, allergies) 3. Any contraindication for Aspirin and Ticagrelor use 4. Other concurrent terminal illnesses with life expectancy less than 1 year (congestive cardiac failure, carcinoma etc.) 5. Current involvement in another clinical trial or exposure to another IMP within the previous 30 days 6. COPD with an atypical cause (e.g. A1antitrypsin deficiency) 7. Planned/ Expected major surgery where anti-platelet therapy would be ceased 8. Pregnancy, planned pregnancy or current breastfeeding 9. Patient is unable to provide informed consent 10. Younger than 18 years |
| Recruitment start date | 04/09/2015 |
| Recruitment end date | 31/05/2017 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Queen Victoria Road
Newcastle Upon Tyne
NE1 4LP
United Kingdom
Freeman Road
Newcastle Upon Tyne
NE7 7DN
United Kingdom
Sponsor information
Hospital/treatment centre
Freeman Hospital
Freeman Road
Newcastle upon Tyne
NE7 7DN
England
United Kingdom
"ROR" |
https://ror.org/05p40t847 |
|---|
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- AstraZeneca PLC, Pearl Therapeutics
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in peer reviewed journals as well as presentation of data at national and international meetings. Results of the study will also be reported to the sponsor and funder. Participants will be informed about their treatment and their contribution to the study at the end of the study, including a lay summary of the results. |
| IPD sharing plan | There currently are no provisions or a plan in place for data sharing for APPLE-COPD. The data are held by NCTU on behalf of the Sponsor. NCTU are currently developing a data sharing policy and it may be possible to make data available in the future. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 26/05/2018 | 17/05/2019 | Yes | No |
| Basic results | 17/06/2020 | No | No | ||
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 05/08/2019 | 08/11/2023 | Yes | No |
Editorial Notes
08/11/2023: Publication reference added.
17/06/2020: Added clinicaltrialsregister.eu link to basic results (scientific).
23/05/2019: IPD sharing statement added.
22/05/2019: The following changes were made to the trial record:
1. Contact details updated.
2. The overall trial end date was changed from 30/11/2018 to 10/11/2017.
3. The total final enrolment number was added.
4. The intention to publish date was changed from 30/11/2018 to 31/12/2019.
21/05/2019: Internal review.
17/05/2019: Publication reference added.
