DIAMOND - Dual Antiplatelet Therapy to Reduce Myocardial Injury

• Sponsor: University of Edinburgh (Other)
• Overall Status: Completed
• CT.gov ID: NCT02110303
• Collaborator: AstraZeneca (Industry)
• Enrollment: 220
• Location: 1
• Arms: 4
• Duration (Months): 37
• Patients Per Site Per Month: 5.9

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: Ticagrelor; Drug: Placebo	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 220 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: May 26, 2017
• Actual Study Completion Date: Apr 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. Plasma high sensitivity cardiac troponin I (hsTnI) concentration in patients with coronary 18F-fluoride uptake. [30 days]

Secondary Outcome Measures

1. Plasma hsTnI concentrations in patients without coronary 18F-fluoride uptake. [30 days]

2. High sensitivity cardiac troponin I (hsTnI) concentration in total study population. [30 days]

3. Plasma high-sensitivity troponin (hsTnI) concentration [1 year]

   In total population and in 18F-F PET positive and negative sub-groups

4. Calcium score and plaque volume at the site of baseline coronary 18F-fluoride uptake [1 year]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Edinburgh Heart Centre	Edinburgh	Lothian	United Kingdom	EH16 4SA

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

Study Documents (Full-Text)

None provided.

More Information

Publications

• Dweck MR, Chow MW, Joshi NV, Williams MC, Jones C, Fletcher AM, Richardson H, White A, McKillop G, van Beek EJ, Boon NA, Rudd JH, Newby DE. Coronary arterial 18F-sodium fluoride uptake: a novel marker of plaque biology. J Am Coll Cardiol. 2012 Apr 24;59(17):1539-48. doi: 10.1016/j.jacc.2011.12.037.
• Joshi NV, Vesey AT, Williams MC, Shah AS, Calvert PA, Craighead FH, Yeoh SE, Wallace W, Salter D, Fletcher AM, van Beek EJ, Flapan AD, Uren NG, Behan MW, Cruden NL, Mills NL, Fox KA, Rudd JH, Dweck MR, Newby DE. 18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial. Lancet. 2014 Feb 22;383(9918):705-13. doi: 10.1016/S0140-6736(13)61754-7. Epub 2013 Nov 11.
• Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators, Freij A, Thorsén M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57. doi: 10.1056/NEJMoa0904327. Epub 2009 Aug 30.

• Responsible Party: University of Edinburgh
• ClinicalTrials.gov Identifier: NCT02110303
• Other Study ID Numbers: DIAMOND-14/SS/0089
• First Posted: Apr 10, 2014
• Last Update Posted: May 10, 2019
• Last Verified: May 1, 2019

• Additional relevant MeSH terms: Coronary Artery Disease; Ticagrelor

Study Results

No Results Posted as of May 10, 2019