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

NCT ID: NCT03487406

Last Updated: 2018-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2017-11-30

Brief Summary

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.

Detailed 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.

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo Ticagrelor & placebo Aspirin

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

Group Type: PLACEBO_COMPARATOR

Placebo Aspirin

Intervention Type: DRUG

Sugar tablet to mimic Aspirin 75 mg tablet One 75 mg tablet, oral, once a day, for 6 months.

Placebo Ticagrelor

Intervention Type: DRUG

Sugar tablet to mimic Ticagrelor 90 mg tablet. Once 90 mg tablet, oral, twice daily for 6 months.

Aspirin & Placebo Ticagrelor

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

Group Type: ACTIVE_COMPARATOR

Aspirin

Intervention Type: DRUG

One 75 mg tablet, oral, once a day, for 6 months.

Placebo Ticagrelor

Intervention Type: DRUG

Sugar tablet to mimic Ticagrelor 90 mg tablet. Once 90 mg tablet, oral, twice daily for 6 months.

Placebo Aspirin & Ticagrelor

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

Group Type: ACTIVE_COMPARATOR

Ticagrelor

Intervention Type: DRUG

One 90 mg tablet, oral, twice daily for 6 months.

Placebo Aspirin

Intervention Type: DRUG

Sugar tablet to mimic Aspirin 75 mg tablet One 75 mg tablet, oral, once a day, for 6 months.

Aspirin & Ticagrelor

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

Group Type: EXPERIMENTAL

Ticagrelor

Intervention Type: DRUG

One 90 mg tablet, oral, twice daily for 6 months.

Aspirin

Intervention Type: DRUG

One 75 mg tablet, oral, once a day, for 6 months.

Interventions

Ticagrelor

One 90 mg tablet, oral, twice daily for 6 months.

Intervention Type: DRUG

Aspirin

One 75 mg tablet, oral, once a day, for 6 months.

Intervention Type: DRUG

Placebo Aspirin

Sugar tablet to mimic Aspirin 75 mg tablet One 75 mg tablet, oral, once a day, for 6 months.

Intervention Type: DRUG

Placebo Ticagrelor

Sugar tablet to mimic Ticagrelor 90 mg tablet. Once 90 mg tablet, oral, twice daily for 6 months.

Intervention Type: DRUG

Other Intervention Names

Brilique

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Newcastle University

OTHER

Sponsor Role: collaborator

Newcastle-upon-Tyne Hospitals NHS Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vijay Kunadian, MBBS MD FRCP

Role: PRINCIPAL_INVESTIGATOR

Intitute of Cellular Medicine, Newcastle University

Locations

Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, , United Kingdom

Countries

United Kingdom

Other Identifiers

2014-005475-86

Identifier Type: -

Identifier Source: org_study_id