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Ticagrelor is one of 3 anti-platelet medications used in patients with acute coronary syndrome (ACS) to prevent further clot formation and further ischemic damage to myocardial tissue. Overall benefits of one drug over the other is neutral in this generally unstable population. In pre-clinical trials, ticagrelor showed secondary effects, involving the release of adenosine to heart muscle where the demand for blood was increased due to a stress condition. Blood flow was increased, potentially preventing potential damage.
This study will compare ticagrelor, currently only approved for use in ACS patients, against clopidogrel by measuring the myocardial blood flow(MBF) during stress to validate this phenomenon. The effect on blood flow will be measurable by using two specific doses of adenosine as the pharmacologic stress and correlating with measurements of blood flow using positron emission tomography (PET) nuclear imaging.
This study hypothesizes that the increase in MBF during intermediate dose adenosine infusion will be greater in ticagrelor treated subjects compared to clopidogrel treated subjects
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| stable CAD management | Experimental | Experimental: Ticagrelor (BrilintaTM) 90 mg tablet by mouth twice a day |
|
| CAD comparison group | Active Comparator | Active comparator: clopidogrel 75 mg plus placebo tablet by mouth twice a day. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ticagrelor | Drug | Blinded administration of ticagrelor for 10 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Differences in rest MBF, stress MBF and MBFR between ticagrelor and clopidogrel treated patients as measured by PET | Blinded study drug will be administered for 10 days after which the subject will undergo MPI imaging to measure MBF. The crossover to the other study arm will occur and the study procedure repeated. Actual study drug effect will not be known until the study has completed and the treatment unblinded. | q 2 weeks blood flow measurements |
| Measure | Description | Time Frame |
|---|---|---|
| The effect of ticagrelor on rest MBF, stress MBF and MBFR will be compared in the normal versus abnormal segments on a segmental and patient basis in the ticagrelor treated subjects | Blinded study drug will be administered for 10 days after which the subject will undergo MPI imaging to measure rest/stress MBF and myocardial blood flow reserve. The crossover to the other study arm will occur and the study procedure repeated. Actual study drug effecting flow will not be known until the study has completed and the treatment unblinded. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Terrence Ruddy, MD | Ottawa Heart Institute Research Corporation | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Ottawa Heart Institute | Ottawa | Ontario | K1Y 4W7 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28465300 | Derived | Pelletier-Galarneau M, Hunter CRRN, Ascah KJ, Beanlands RSB, Dwivedi G, deKemp RA, Chow BJW, Ruddy TD. Randomized Trial Comparing the Effects of Ticagrelor Versus Clopidogrel on Myocardial Perfusion in Patients With Coronary Artery Disease. J Am Heart Assoc. 2017 May 2;6(5):e005894. doi: 10.1161/JAHA.117.005894. |
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| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000077486 | Ticagrelor |
| D000077144 | Clopidogrel |
| ID | Term |
|---|---|
| D000241 | Adenosine |
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
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| Clopidogrel | Drug | Blinded administration of clopidogrel and placebo for 10 days |
|
| q 2 weeks blood flow measurements |
| D001161 |
| Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |