DIAMOND - Dual Antiplatelet Therapy to Reduce Myocardial Injury

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 by University of Edinburgh
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT02110303
First received: April 7, 2014
Last updated: April 28, 2014
Last verified: April 2014
  Purpose

Heart attacks are most commonly caused by rupture of fatty deposits (plaques) within the wall of heart blood vessels. It appears that this process can also frequently occur without causing any symptoms and these events likely explain the development of narrowing within the heart arteries which can subsequently produce symptoms of angina (chest pain).

Previous research has shown a specialised scanner known as a PET (positron emission tomography) scan can identify these recently ruptured plaques in patients without symptoms of a heart attack and these patients have changes on a blood test (troponin) which suggest that they are at higher risk of having a heart attack in the future. This study aims to identify these patients using the PET scan and then see if the markers of increased heart attack risk can be reduced by the use of a blood thinning medication (ticagrelor) which is already a well recognised treatment for people who have suffered a recent heart attack.


Condition Intervention Phase
Coronary Artery Disease
Drug: Ticagrelor
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Dual Antiplatelet Therapy to Inhibit Coronary Atherosclerosis and Myocardial Injury in Patients With Necrotic High-Risk Coronary Plaque Disease

Resource links provided by NLM:


Further study details as provided by University of Edinburgh:

Primary Outcome Measures:
  • Plasma high sensitivity cardiac troponin I (hsTnI) concentration in patients with coronary 18F-fluoride uptake. [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma hsTnI concentrations in patients without coronary 18F-fluoride uptake. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • High sensitivity cardiac troponin I (hsTnI) concentration in total study population. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Plasma high-sensitivity troponin (hsTnI) concentration [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    In total population and in 18F-F PET positive and negative sub-groups

  • Calcium score and plaque volume at the site of baseline coronary 18F-fluoride uptake [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 250
Study Start Date: June 2014
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 18F-F Positive - Ticagrelor
Ticagrelor oral tablets, one (90mg) tablet, twice daily, 12 month duration
Drug: Ticagrelor
oral, 90mg tablets, twice daily, 12 month duration
Other Names:
  • Brilique
  • Brilinta
  • Possia
  • AZD6140
  • SUB30898
  • B01AC24
Placebo Comparator: 18F-F Positive - Placebo
Identical placebo, one tablet, twice daily, 12 month duration
Drug: Placebo
Oral tablet (identical to ticagrelor), twice daily, 12 month duration
Experimental: 18F-F Negative - Ticagrelor
Ticagrelor oral tablets, one (90mg) tablet, twice daily, 12 month duration
Drug: Ticagrelor
oral, 90mg tablets, twice daily, 12 month duration
Other Names:
  • Brilique
  • Brilinta
  • Possia
  • AZD6140
  • SUB30898
  • B01AC24
Placebo Comparator: 18F-F Negative - Placebo
Identical placebo, one tablet, twice daily, 12 month duration
Drug: Placebo
Oral tablet (identical to ticagrelor), twice daily, 12 month duration

Detailed Description:

The investigators aim to recruit patients with multivessel, clinically stable coronary artery disease. Patients will undergo baseline investigations including CT-PET imaging using 18F-Sodium Fluoride (18F-F) tracer to detect potentially unstable coronary plaques. The groups will be separated into those with and without 18F-F uptake. Each of these groups will be randomised to receive oral ticagrelor or a matched placebo in addition to their usual medications. Patients will remain on aspirin but will not be eligible for the trial if taking additional antiplatelet/anticoagulant treatments. The treatment will be continued for 1 year.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients aged ≥40 years with angiographically proven multivessel coronary artery disease defined as at least two major epicardial vessels with any combination of either (a) >50% luminal stenosis, or (b) previous revascularization (percutaneous coronary intervention or coronary artery bypass graft surgery).
  • Provision of informed consent prior to any study specific procedures

Exclusion Criteria:

  • An acute coronary syndrome within the last 12 months
  • An indication for dual anti-platelet therapy, such as drug eluting stent
  • Inability to take aspirin
  • Receiving thienopyridine therapy such as clopidogrel or prasugrel
  • Percutaneous coronary intervention or coronary artery bypass graft surgery within the last 3 months
  • Inability or unwilling to give informed consent
  • Woman with child-bearing potential and who are breastfeeding will not be enrolled into the trial (woman who have experienced menarche, are pre-menopausal, have not been sterilised or who are currently pregnant)
  • Known hypersensitivity to ticagrelor or one of its excipients
  • Active pathological bleeding or bleeding diathesis
  • Significant thrombocytopenia: <100 x 10^9 /L
  • History of intracranial haemorrhage
  • Moderate to severe liver impairment (Child's Grade B or C)
  • Maintenance therapy with strong cytochrome P450 3A4 (CYP3A4) inhibitors, such as ketoconazole, nefazodone, ritonavir, indinavir, atazanavir, or clarithromycin
  • Major intercurrent illness or life expectancy <1 year
  • Renal dysfunction (eGFR ≤30 mL/min/1.73 m2)
  • Contraindication to iodinated contrast agents
  • Planned coronary revascularization or major non-cardiac surgery in the next 12 months
  • Maintenance therapy with simvastatin at doses greater than 40mg daily
  • Receiving oral anticoagulants including warfarin, rivaroxaban, dabigatran or apixaban.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02110303

Contacts
Contact: David E. Newby, PhD +44 131 242 6515 d.e.newby@ed.ac.uk

Locations
United Kingdom
Edinburgh Heart Centre Not yet recruiting
Edinburgh, Lothian, United Kingdom, EH10 4SA
Principal Investigator: Philip D. Adamson, MBChB         
Sponsors and Collaborators
University of Edinburgh
AstraZeneca
Investigators
Study Chair: David E. Newby, PhD University of Edinburgh
Principal Investigator: Philip D. Adamson, MBChB University of Edinburgh
  More Information

Publications:
Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT02110303     History of Changes
Other Study ID Numbers: DIAMOND-14/SS/0055
Study First Received: April 7, 2014
Last Updated: April 28, 2014
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Wounds and Injuries
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Ticagrelor
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 26, 2014