Clinical trial NCT03487406: Anti-platelet Therapy in the Prevention of Cardiovascular Disease in Patients With COPD (APPLE-COPD: ICON 2)
Official title: Anti-platelet Therapy in the Primary Prevention of Cardiovascular Disease in Patients With Chronic Obstructive Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Lead sponsor: Newcastle-upon-Tyne Hospitals NHS Trust
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: Newcastle University
First posted: 2018-04-04
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in baseline ASPI and ADP-induced platelet aggregation at 6 months
timeFrame: Baseline to 6 months
Secondary outcomes:
measure: Change in inflammatory markers (myeloperoxidase (MPO) measured by routine blood test at baseline, 1 month and 6 months
timeFrame: Baseline to 6 months
measure: Change in inflammatory markers (interleukin-6 (IL-6) measured by routine blood test at baseline, 1 month and 6 months
timeFrame: Baseline to 6 months
measure: Change in inflammatory markers (fibrinogen) measured by routine blood test at baseline, 1 month and 6 months
timeFrame: Baseline to 6 months
measure: Change in inflammatory markers (high sensitive C reactive protein (hsCRP) measured by routine blood test at baseline, 1 month and 6 months
timeFrame: Baseline to 6 months
measure: Change in inflammatory markers (tumor necrosis factor alpha (TNF) measured by routine blood test at baseline, 1 month and 6 months
timeFrame: Baseline to 6 months
measure: Changes in carotid intima media thickness
timeFrame: Baseline to 6 months
measure: Changes in vascular stiffness (m/s)
timeFrame: Baseline and 6-months
measure: Quality of life using EuroQoL-5D-5L health-related quality of life instrument
timeFrame: Baseline and 6-months
measure: St George's Respiratory Questionnaire for Chronic Obstructive Pulmonary Disease Patients (SGRQ-C)
timeFrame: Baseline and 6-months
Other outcomes:
measure: Rates of major and minor bleeding as defined by the TIMI scale
timeFrame: Baseline to 6 months
measure: Rates of major and minor bleeding as defined by the Bleeding Academic Research Consortium (BARC) definition.
timeFrame: Baseline to 6 months
measure: Response on spirometry using the MRC dyspnoea scale (Breathlessness)
timeFrame: Baseline to 6 months
measure: Forced Expiratory Volume (FEV1) and Forced Vital Capacity (FVC) measured by spirometry
timeFrame: Baseline to 6 months
Locations:
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle upon Tyne Hospitals NHS Foundation Trust
Study officials:
affiliation: Intitute of Cellular Medicine, Newcastle University
name: Vijay Kunadian, MBBS MD FRCP
role: PRINCIPAL_INVESTIGATOR
References: