Anti-platelet Therapy in the Prevention of Cardiovascular Disease in Patients With COPD (APPLE-COPD: ICON 2)

Newcastle-upon-Tyne Hospitals NHS Trust

Status and phase: Completed; Phase 2

Conditions: Chronic Obstructive Pulmonary Disease (COPD)

Treatments: Drug: Placebo Aspirin; Drug: Ticagrelor; Drug: Placebo Ticagrelor; Drug: Aspirin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03487406

2014-005475-86

Details and patient eligibility

About

Patients with COPD (chronic bronchitis and/or emphysema) are known to be at an increased risk of heart disease and death due to heart attacks. There are several possible reasons for this, one of which is an increased tendency of the blood to clot, that can give rise to blood clot formation in the coronary arteries, and lead to heart attack. Medications such as Aspirin and another new blood thinning tablet called Ticagrelor are already used for patients with heart attacks. Given that patients with COPD are at higher risk of heart attack, the investigators wish to see if these tablets that can prevent blood clot formation in heart arteries might also prevent heart attacks happening in COPD patients. The investigators hope to understand the effects by measuring clotting and inflammation in the blood. All patients will be followed up for 6-months.

In addition the investigators wish to study COPD patients who do not have a high risk of developing future heart problems using the QRISK score to study their well being over a 1 year period to see if they might also benefit from blood thinning medications.

Full description

The APPLE-COPD: ICON2 trial is a double blinded, proof-of-concept, randomised controlled trial that will include patients who have not been previously targeted in clinical cardiovascular research. The study will consist of patients with a lung condition called chronic obstructive pulmonary disease (COPD) who have not previously been diagnosed with coronary artery disease (CAD) and yet are at higher risk of CAD, myocardial infarction, and excess mortality (as determined by QRISK2 score). The QRISK2 is a simple questionnaire for heart disease that uses well known risk factors such as age, high blood pressure, smoking status and abnormal cholesterol levels. A QRISK score over 20 (20% risk of a cardiovascular event over the next ten years) is already used as a prompt to consider cholesterol lowering therapy (such as statins).

Patients with COPD (chronic bronchitis and/or emphysema) are known to be at an increased risk of heart disease and death due to heart attacks. There are several possible reasons for this, one of which is an increased tendency of the blood to clot which can give rise to blood clot formation in the coronary arteries, and lead to heart attack. Medications such as Aspirin and another new blood thinning tablet called Ticagrelor are already used for patients with heart attacks. Given that patients with COPD are at higher risk of heart attack, the investigators wish to see if these tablets that can prevent blood clot formation in heart arteries, might also prevent heart attacks happening in COPD patients. The investigators hope to understand the effects by measuring clotting and inflammation in the blood.

Aspirin and Ticagrelor are widely used in the UK for the management of coronary artery disease. For purposes of this study, Aspirin and Ticagrelor will be treated as an Investigational Medicinal Product (IMP). As a 2x2 factorial design, the primary analyses are based on a comparison of i) Aspirin vs no Aspirin and ii) Ticagrelor vs. no Ticagrelor (resulting in 4 treatment arms). Treatment allocation will be blinded to both the investigator and the participant.

Participants allocated to the treatment arms will be requested to take their trial medication for 6 months and will then be followed up clinically for a further 6 months by the research team to monitor any adverse events and the participant's well-being.

Participants allocated to the observational arm will be followed up for 1 year.

At 1 year all trial procedures will end and the patient will continue to receive routine care by the clinical care team.

Enrollment: 120 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Abnormal spirometry with FEV1<80% and FEV1/FVC ratio <70% of predicted
• Smoking history that is 10-pack years or greater (current or ex smokers can be included)
• Have capacity to consent

Exclusion criteria

• Any condition that is being concurrently treated through anticoagulation or antiplatelet therapy including Aspirin (any form of Aspirin) or Ticagrelor (atrial fibrillation, deep vein thrombosis, valve prosthesis, recent myocardial infarction, use of drug eluting stents)
• Other specific contraindications to management with antiplatelet medication (bleeding risks, allergies)
• Any contraindication for Aspirin and Ticagrelor use
• Other concurrent terminal illnesses with life expectancy less than 1 year (congestive cardiac failure, carcinoma etc)
• Current involvement in another clinical trial or exposure to another IMP within the previous 30 days
• COPD with an atypical cause (e.g. A1- antitrypsin deficiency)
• Patients who are unable to provide informed consent
• Planned/ Expected major surgery where anti-platelet therapy would be ceased
• Pregnancy, planned pregnancy or current breast-feeding

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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120 participants in 4 patient groups, including a placebo group

Placebo Ticagrelor & placebo Aspirin

Placebo Comparator group

Description:

Placebo Ticagrelor 90 mg- one tablet, twice daily. Placebo Aspirin 75 mg- one tablet, once a day.

Treatment:

Drug: Placebo Ticagrelor

Drug: Placebo Aspirin

Aspirin & Placebo Ticagrelor

Active Comparator group

Description:

Aspirin 75mg - one tablet, once a day. Placebo Ticagrelor 90 mg- one tablet, twice daily.

Treatment:

Drug: Placebo Ticagrelor

Drug: Aspirin

Placebo Aspirin & Ticagrelor

Active Comparator group

Description:

Placebo Aspirin 75 mg - one tablet, once a day. Ticagrelor 90 mg- one tablet, twice daily.

Treatment:

Drug: Ticagrelor

Drug: Placebo Aspirin

Aspirin & Ticagrelor

Experimental group

Description:

Aspirin 75 mg - one tablet, once a day. Ticagrelor 90 mg- one tablet, twice daily.

Treatment:

Drug: Ticagrelor

Drug: Aspirin