Ticagrelor Versus High-dose Clopidogrel in Patients With High Platelet Reactivity on Clopidogrel After PCI

Study Overview
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Brief Summary
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To determine the safety and efficacy of Ticagrelor versus Clopidogrel for the reduction of adverse cardiovascular outcomes in patients with high platelet reactivity on clopidogrel after successful implantation of coronary drug-eluting stents.

Detailed Description
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This is a multi-center, randomized, single-blind, investigator-initiated study with a parallel design. Patients with coronary artery disease undergoing percutaneous coronary intervention and presenting high platelet reactivity on clopidogrel as assessed with the PL-11 analyzer (platelet maximum aggregation ratio [MAR%] ≥ 55 %) at 2 hours post-clopidogrel 300mg LD (Day 0), will be randomized after informed consent, in a 1:1 ratio to the following treatment groups: Group Α: Ticagrelor 180 mg immediate loading (on Day 0) followed by 180mg/day starting from Day 1 until Day 365 (12 months after randomization). Group Β: Clopidogrel 150mg per day, starting from Day 1 until Day 365 (12 months after randomization). Platelet reactivity assessment will be performed before randomization (Day 0), and 3-day after randomization (Day 3). Documentation of major adverse cardiac and cerebrovascular events (death, myocardial infarction, stent thrombosis, stroke, revascularization procedure with PCI or CABG) and serious adverse events (bleeding, other adverse events) will be performed until 12 months.

Official Title
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Ticagrelor Versus High-dose Clopidogrel in Patients With High Platelet Reactivity on Clopidogrel After Percutaneous Coronary Intervention: The PL-PLATELET Randomized Trial

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Ticagrelor
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who agreed to the experimental plan which was permitted by IRB; Patients planned to take dual antiplatelet therapy for 12 months. Exclusion Criteria: Severe hepatic dysfunction defined as serum transaminase > 3 times normal limit; Renal dysfunction defined as eGFR < 30ml/min/1.73m^2; Co-morbidity with an estimated life expectancy of < 50 % at 12 months; Scheduled surgery in the next 12 months, which resulted protocol changes; Known allergy against study drug or device; Use of glycoprotein IIb/IIIa inhibitor during the perioperative period; Anticoagulation treatment including warfarin.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ticagrelor<br>Administration of ticagrelor 180mg/day for 12 months. | Drug: Ticagrelor<br>* Daily administration of ticagrelor 180mg for 12 months<br>* Other names: BRILINTA;|
| Active Comparator: Clopidogrel<br>Administration of clopidogrel 150 mg/day for 12 months | Drug: Clopidogrel<br>* Daily administration of clopidogrel 150mg for 12 months<br>* Other names: Plavix, Talcom;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12-Month Freedom From MACE | Major adverse cardiovascular and cerebrovascular events consist of all-cause death, target vessel myocardial infarction, stroke, stent thrombosis. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12-Month Freedom From Mortality | All-cause death | 12 months | 
| 12-Month Freedom From Cardiac death | Cardiac death | 12 months | 
| 12-Month Freedom From MI | Myocardial infarction | 12 months | 
| 12-Month Freedom From TLR | Target lesion revascularisation | 12 months | 
| 12-Month Freedom From TVR | Target vessel revascularisation | 12 months | 
| 12-Month Freedom From Stent Thrombosis | Stent thrombus was classified as definite, probable, or possible, according to the definitions provided by the Academic Research Consortium (ARC).Regarding timing, ST was defined as early (<30 days), late (30 days to 1 year), or too late (>1 year). | 12 months | 
| 12-Month Freedom From Stroke | Stroke | 12 months |