Platelet Sub-study of the TWILIGHT Trial

Study Overview
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Brief Summary
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TWILIGHT study is a multicenter RCT comparing treatment with ticagrelor alone versus ticagrelor plus aspirin in high-risk patients after PCI. All patients will receive DAPT (ticagrelor plus aspirin) for the initial 3 months post-PCI and then be randomized to either Ticagrelor alone OR Ticagrelor plus Aspirin DAPT. To investigate the pharmacodynamic effects of the two treatments in this trial, a 'Platelet Sub-study' will be conducted only at the Mount Sinai Medical Center. The sub-study will recruit randomized patients from the TWILIGHT Trial at Mount Sinai and conduct specialized blood tests at randomization and one month thereafter. The aim of the Platelet Sub-study is to compare the antithrombotic effects of Ticagrelor alone versus Ticagrelor plus Aspirin using an ex vivo model of thrombosis (Badimon Chamber).

Detailed Description
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The present study will enroll a cohort of randomized patients from the TWILIGHT trial at the Mount Sinai Medical Center. These subjects will undergo blood sampling and measurement of thrombotic indices at the time of randomization and 1-6 months thereafter.

Official Title
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Platelet Sub-study of the TWILIGHT Trial

Conditions
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Coronary Artery Disease, Myocardial Infarction

Intervention / Treatment
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* Drug: Ticagrelor
* Drug: ASA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients enrolled in the TWILIGHT trial: Clinical Inclusion Criteria (must meet at least one): Adult patients ≥ 65 years of age Troponin (+) acute coronary syndrome Female gender Established vascular disease defined as previous MI, documented PAD or CAD/PAD revascularization Diabetes mellitus treated with medications (oral hypoglycemic, subcutaneous injection of insulin) Chronic kidney disease defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 or creatinine clearance (CrCl) < 60 ml/min Angiographic Inclusion Criteria (must meet at least one): Multivessel coronary artery disease Target lesion requiring total stent length >30 mm Thrombotic target lesion(s) Bifurcation lesions with Medina X,1,1 classification requiring at least 2 stents Left main (≥50%) or proximal LAD (≥70%) lesion Calcified target lesion(s) requiring atherectomy Exclusion Criteria: Patients not eligible to participate in the TWILIGHT trial: Under 18 years of age Contraindication to aspirin Contraindication to ticagrelor Planned surgery within 90 days Planned coronary revascularization (surgical or percutaneous) within 90 days Need for chronic oral anticoagulation Prior stroke Dialysis-dependent renal failure Active bleeding or extreme-risk for major bleeding (e.g. active peptic ulcer disease, gastrointestinal pathology with a raised risk for bleeding, malignancies with a raised risk for bleeding) Emergent or salvage PCI or STEMI presentation. Liver cirrhosis Life expectancy < 1 year Unable or unwilling to provide informed consent Women of child bearing potential (as determined by hospital standard of care) Fibrinolytic therapy within 24 hours of index PCI Concomitant therapy with a strong cytochrome P-450 3A inhibitor or inducer Platelet count < 100,000 mm3 Requiring ongoing treatment with aspirin > 325 mg daily.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Ticagrelor<br>Ticagrelor 90mg tablet bid for 12 months | Drug: Ticagrelor<br>* 90mg tablet bid for 12 months<br>|
| Ticagrelor + ASA<br>Ticagrelor 90mg tablet bid for 12 months and enteric coated aspirin 81mg-100mg daily p.o. for 12 months | Drug: Ticagrelor<br>* 90mg tablet bid for 12 months<br>Drug: ASA<br>* enteric coated aspirin 81mg-100mg daily p.o. for 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thrombus size (Badimon Chamber) | Thrombus area measured 1-6 months after randomization | 1-6 months after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet aggregation | Platelet aggregation assessed using Multiplate Analyzer 1-6 months after randomization | 1-6 months after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thrombosis, Platelets, Platelet Aggregation, Blood Thrombogenicity