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

Phase 4

• Conditions: End-Stage Renal Disease; Acute Coronary Syndrome; Chronic Kidney Disease
• Interventions: Drug: Clopidogrel first; Drug: Ticagrelor first

• Registration Number: NCT02459288
• Lead Sponsor: Ping-Yen Liu

Brief Summary

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

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.

Study Timeline

• Study Start: 2014-01
• Study First Submitted: 2014-09-23
• Status Verified: 2015-05
• Study First Submitted QC: 2015-05-28
• Last Update Submitted: 2015-05-28
• Study First Posted: 2015-06-02
• Last Update Posted: 2015-06-02
• Primary Completion: 2015-12
• Study Completion: 2015-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Provision of informed consent prior to any study specific procedures
2. Female and male, age between 20-75 years
3. Stage 3-5 chronic kidney disease (eGFR<60ml/min) patients or ESRD
4. Taking standard treatment dose of clopidogrel (75mg/day) for more than 1 week
5. 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.
6. 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).
7. 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

1. Oral anticoagulation therapy that cannot be stopped
2. Increased risk of bradycardia
3. Concomitant use of strong CYP3A inhibitor/inducers
4. Unwilling to sign inform consent
5. Allergic or contraindicated to any study medications

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Clopidogrel first	Clopidogrel first	Clopidogrel (Plavix) 75 mg qd, 2 weeks; followed with Ticagrelor (Brilinta) 90 mg bd, 2 weeks
Ticagrelor first	Ticagrelor first	Ticagrelor (Brilinta) 90 mg bd, 2 weeks; followed with Clopidogrel (Plavix) 75 mg qd, 2 weeks

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Major bleeding events	1 year	assessed by TIMI bleeding score: mild, moderate and severe; the transfusion of packed red blood cell amount; decreased count in Hb (\>2.5)

Trial Locations

Locations (1)

Department of Internal Medicine, National Cheng Kung University Hospital; 🇨🇳 Tainan, Taiwan