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

NCT03487406 | Completed Phase 2

• 1 other identifier: 2014-005475-86
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Outcome Measures

Primary Outcomes (1)

• Change in baseline ASPI and ADP-induced platelet aggregation at 6 months

  The primary outcome measure is platelet reactivity measured at 6-months. Response is calculated according to high platelet reactivity (HPR). Rates of HPR will be determined according to recently published definitions of HPR for multiple electrode aggregometry in patients undergoing percutaneous coronary intervention, \>46 AU for ADP test and \>40 for ASPI test. Response rate will be calculated on an intention to treat basis as the total number of patients responding as a proportion of all patients randomised and reported descriptively with 95% confidence intervals. Any patients who are not assessable at 6-months will be classed as a non-responder.

  Baseline to 6 months

Secondary Outcomes (9)

• Change in inflammatory markers (myeloperoxidase (MPO) measured by routine blood test at baseline, 1 month and 6 months

  Baseline to 6 months

• Change in inflammatory markers (interleukin-6 (IL-6) measured by routine blood test at baseline, 1 month and 6 months

  Baseline to 6 months

• Change in inflammatory markers (fibrinogen) measured by routine blood test at baseline, 1 month and 6 months

  Baseline to 6 months

• Change in inflammatory markers (high sensitive C reactive protein (hsCRP) measured by routine blood test at baseline, 1 month and 6 months

  Baseline to 6 months

• Change in inflammatory markers (tumor necrosis factor alpha (TNF) measured by routine blood test at baseline, 1 month and 6 months

  Baseline to 6 months

Other Outcomes (4)

• Rates of major and minor bleeding as defined by the TIMI scale

  Baseline to 6 months

• Rates of major and minor bleeding as defined by the Bleeding Academic Research Consortium (BARC) definition.

  Baseline to 6 months

• Response on spirometry using the MRC dyspnoea scale (Breathlessness)

  Baseline to 6 months

Study Arms (4)

Placebo Ticagrelor & placebo Aspirin

PLACEBO COMPARATOR

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

Drug: Placebo Aspirin; Drug: Placebo Ticagrelor

Aspirin & Placebo Ticagrelor

ACTIVE COMPARATOR

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

Drug: Aspirin; Drug: Placebo Ticagrelor

Placebo Aspirin & Ticagrelor

ACTIVE COMPARATOR

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

Drug: Ticagrelor; Drug: Placebo Aspirin

Aspirin & Ticagrelor

EXPERIMENTAL

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

Drug: Ticagrelor; Drug: Aspirin

Interventions

Ticagrelor DRUG

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

Also known as: Brilique

Aspirin & Ticagrelor; Placebo Aspirin & Ticagrelor

Aspirin DRUG

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

Aspirin & Placebo Ticagrelor; Aspirin & Ticagrelor

Placebo Aspirin DRUG

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

Placebo Aspirin & Ticagrelor; Placebo Ticagrelor & placebo Aspirin

Placebo Ticagrelor DRUG

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

Aspirin & Placebo Ticagrelor; Placebo Ticagrelor & placebo Aspirin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Newcastle-upon-Tyne Hospitals NHS Trust: lead
• AstraZeneca: collaborator
• Newcastle University: collaborator

Study Sites (1)

Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Ticagrelor; Aspirin

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Vijay Kunadian, MBBS MD FRCP

  Intitute of Cellular Medicine, Newcastle University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2015
• First Posted: April 4, 2018
• Study Start: September 1, 2015
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: April 4, 2018

Record last verified: 2018-03

Locations

GB (1)