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DIAMOND - Dual Antiplatelet Therapy to Reduce Myocardial Injury (DIAMOND)

Primary Purpose

Coronary Artery Disease

Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Ticagrelor
Placebo
Sponsored by
University of Edinburgh
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronary Artery Disease

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Edinburgh Heart Centre

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

18F-F Positive - Ticagrelor

18F-F Positive - Placebo

18F-F Negative - Ticagrelor

18F-F Negative - Placebo

Arm Description

Ticagrelor oral tablets, one (90mg) tablet, twice daily, 12 month duration

Identical placebo, one tablet, twice daily, 12 month duration

Ticagrelor oral tablets, one (90mg) tablet, twice daily, 12 month duration

Identical placebo, one tablet, twice daily, 12 month duration

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Plasma hsTnI concentrations in patients without coronary 18F-fluoride uptake.
High sensitivity cardiac troponin I (hsTnI) concentration in total study population.
Plasma high-sensitivity troponin (hsTnI) concentration
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

Full Information

First Posted
April 7, 2014
Last Updated
May 9, 2019
Sponsor
University of Edinburgh
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT02110303
Brief Title
DIAMOND - Dual Antiplatelet Therapy to Reduce Myocardial Injury
Acronym
DIAMOND
Official Title
Dual Antiplatelet Therapy to Inhibit Coronary Atherosclerosis and Myocardial Injury in Patients With Necrotic High-Risk Coronary Plaque Disease
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
March 2015 (undefined)
Primary Completion Date
May 26, 2017 (Actual)
Study Completion Date
April 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Edinburgh
Collaborators
AstraZeneca

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
220 (Actual)

8. Arms, Groups, and Interventions

Arm Title
18F-F Positive - Ticagrelor
Arm Type
Experimental
Arm Description
Ticagrelor oral tablets, one (90mg) tablet, twice daily, 12 month duration
Arm Title
18F-F Positive - Placebo
Arm Type
Placebo Comparator
Arm Description
Identical placebo, one tablet, twice daily, 12 month duration
Arm Title
18F-F Negative - Ticagrelor
Arm Type
Experimental
Arm Description
Ticagrelor oral tablets, one (90mg) tablet, twice daily, 12 month duration
Arm Title
18F-F Negative - Placebo
Arm Type
Placebo Comparator
Arm Description
Identical placebo, one tablet, twice daily, 12 month duration
Intervention Type
Drug
Intervention Name(s)
Ticagrelor
Other Intervention Name(s)
Brilique, Brilinta, Possia, AZD6140, SUB30898, B01AC24
Intervention Description
oral, 90mg tablets, twice daily, 12 month duration
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral tablet (identical to ticagrelor), twice daily, 12 month duration
Primary Outcome Measure Information:
Title
Plasma high sensitivity cardiac troponin I (hsTnI) concentration in patients with coronary 18F-fluoride uptake.
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Plasma hsTnI concentrations in patients without coronary 18F-fluoride uptake.
Time Frame
30 days
Title
High sensitivity cardiac troponin I (hsTnI) concentration in total study population.
Time Frame
30 days
Title
Plasma high-sensitivity troponin (hsTnI) concentration
Description
In total population and in 18F-F PET positive and negative sub-groups
Time Frame
1 year
Title
Calcium score and plaque volume at the site of baseline coronary 18F-fluoride uptake
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David E. Newby, PhD
Organizational Affiliation
University of Edinburgh
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Philip D. Adamson, MBChB
Organizational Affiliation
University of Edinburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
Edinburgh Heart Centre
City
Edinburgh
State/Province
Lothian
ZIP/Postal Code
EH16 4SA
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
24224999
Citation
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.
Results Reference
background
PubMed Identifier
22516444
Citation
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.
Results Reference
background
PubMed Identifier
19717846
Citation
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, Thorsen 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.
Results Reference
background
PubMed Identifier
33297761
Citation
Doris MK, Meah MN, Moss AJ, Andrews JPM, Bing R, Gillen R, Weir N, Syed M, Daghem M, Shah A, Williams MC, van Beek EJR, Forsyth L, Dey D, Slomka PJ, Dweck MR, Newby DE, Adamson PD. Coronary 18F-Fluoride Uptake and Progression of Coronary Artery Calcification. Circ Cardiovasc Imaging. 2020 Dec;13(12):e011438. doi: 10.1161/CIRCIMAGING.120.011438. Epub 2020 Dec 10.
Results Reference
derived
PubMed Identifier
31422134
Citation
Moss AJ, Dweck MR, Doris MK, Andrews JPM, Bing R, Forsythe RO, Cartlidge TR, Pawade TA, Daghem M, Raftis JB, Williams MC, van Beek EJR, Forsyth L, Lewis SC, Lee RJ, Shah ASV, Mills NL, Newby DE, Adamson PD. Ticagrelor to Reduce Myocardial Injury in Patients With High-Risk Coronary Artery Plaque. JACC Cardiovasc Imaging. 2020 Jul;13(7):1549-1560. doi: 10.1016/j.jcmg.2019.05.023. Epub 2019 Aug 14.
Results Reference
derived
PubMed Identifier
31382765
Citation
Moss AJ, Doris MK, Andrews JPM, Bing R, Daghem M, van Beek EJR, Forsyth L, Shah ASV, Williams MC, Sellers S, Leipsic J, Dweck MR, Parker RA, Newby DE, Adamson PD. Molecular Coronary Plaque Imaging Using 18F-Fluoride. Circ Cardiovasc Imaging. 2019 Aug;12(8):e008574. doi: 10.1161/CIRCIMAGING.118.008574. Epub 2019 Aug 6.
Results Reference
derived

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DIAMOND - Dual Antiplatelet Therapy to Reduce Myocardial Injury

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