Platelet Resistance With Ticagrelor or Standard-Dose Clopidogrel Among CKD and ACS Patients

Study Overview
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Brief Summary
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A 4 week-duration cross-over study on Ticagrelor and Clopidogrel for the Acute Coronary Syndrome (ACS) and Chronic Kidney Disease (CKD) subjects, focusing on the platelet inhibition and safety observation.

Detailed Description
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Acute coronary syndrome is a high mortality and costly disease. Antiplatelet therapies, including aspirin and P2Y12 antagonist, play important roles at the acute and subacute stage treatment for acute coronary syndrome, especially after coronary stent implantation. Patients with decreased estimated glomerular filtration rate (eGFR) experience higher cardiovascular morbidity and mortality. Clopidogrel, one of P2Y12 receptor antagonists, inhibits the receptor's activation by blocking its interaction with ADP. However, the efficacy of clopidogrel shows substantial variation and residual platelet reactivity, which is related to adverse cardiovascular outcome, especially in impaired renal function. Our study aims to check the platelet inhibition rate comparing both medication with a cross-over study among CKD subjects and ACS condition.

Official Title
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A comParison on Platelet Resistance With Ticagrelor or Standard-Dose Clopidogrel Study Among SeVerE Chronic Kidney Disease/ End-Stage-Renal-Disease Patients With Recent Acute Coronary Syndrome.

Conditions
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Acute Coronary Syndrome, Chronic Kidney Disease, End-Stage Renal Disease

Intervention / Treatment
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* Drug: Clopidogrel first
* Drug: Ticagrelor first


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent prior to any study specific procedures Female and male, age between 20-75 years Stage 3-5 chronic kidney disease (eGFR<60ml/min) patients or ESRD Taking standard treatment dose of clopidogrel (75mg/day) for more than 1 week Patients were eligible for enrollment if they were hospitalized for an acute coronary syndrome, with or without ST-segment elevation, with an onset of symptoms during the past 6 months. For patients who had an acute coronary syndrome without ST-segment elevation, at least two of the following three criteria had to be met: ST-segment changes on electrocardiography, indicating ischemia; a positive test of a biomarker, indicating myocardial necrosis; or one of several risk factors (age ≥60 years; previous myocardial infarction or coronary-artery bypass grafting [CABG]; coronary artery disease with stenosis of ≥50% in at least two vessels; previous ischemic stroke, transient ischemic attack, carotid stenosis of at least 50%, or cerebral revascularization; diabetes mellitus; peripheral arterial disease). For patients who had an acute coronary syndrome with ST-segment elevation, the following two inclusion criteria had to be met: persistent ST-segment elevation of at least 0.1 mV in at least two contiguous leads or a new left bundle-branch block. Exclusion Criteria: Oral anticoagulation therapy that cannot be stopped Increased risk of bradycardia Concomitant use of strong CYP3A inhibitor/inducers Unwilling to sign inform consent Allergic or contraindicated to any study medications

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clopidogrel first<br>Clopidogrel (Plavix) 75 mg qd, 2 weeks; followed with Ticagrelor (Brilinta) 90 mg bd, 2 weeks | Drug: Clopidogrel first<br>* After randomization, 2 weeks Clopidogrel (Plavix) 75 mg QD will be given and then crossover with following 2 weeks Ticagrelor (Brilinta) 90 mg bd<br>* Other names: C-T;|
| Experimental: Ticagrelor first<br>Ticagrelor (Brilinta) 90 mg bd, 2 weeks; followed with Clopidogrel (Plavix) 75 mg qd, 2 weeks | Drug: Ticagrelor first<br>* After randomization, 2 weeks Ticagrelor (Brilinta) 90 mg bd will be given then crossover with following 2 weeks Clopidogrel (Plavix) 75 mg QD<br>* Other names: T-C;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| platelet VerifyNow inhibition rate and Platelet Residual Unit (PRU) values changes |  | baseline, 2 weeks and 4 weeks later (compare cross over effect) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major bleeding events | assessed by TIMI bleeding score: mild, moderate and severe; the transfusion of packed red blood cell amount; decreased count in Hb (>2.5) | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute coronary syndrome, Chronic kidney disease, End-Stage Renal Disease, eGFR, Ticagrelor, Clopidogrel