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

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.

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.

Study Overview

• Status: Unknown
• Conditions: Chronic Kidney Disease; Acute Coronary Syndrome; End-Stage Renal Disease
• Intervention / Treatment: Drug: Clopidogrel first; Drug: Ticagrelor first

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 Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan, 704
    • Recruiting
    • Department of Internal Medicine, National Cheng Kung University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial infarction		1 year
emergent condition with hospitalization need	Number of subjects with an emergent condition that required hospitalization	30 days

Collaborators and Investigators

• Sponsor: Ping-Yen Liu
• Investigators: Principal Investigator: Ping-Yen Liu, MD, PhD., National Cheng Kung University

Publications and helpful links

General Publications

• Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: September 23, 2014
• First Submitted That Met QC Criteria: May 28, 2015
• First Posted (Estimate): June 2, 2015

Study Record Updates

• Last Update Posted (Estimate): June 2, 2015
• Last Update Submitted That Met QC Criteria: May 28, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Ticagrelor; Acute coronary syndrome; Chronic kidney disease; Clopidogrel; eGFR; End-Stage Renal Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Disease; Renal Insufficiency; Syndrome; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel
• Other Study ID Numbers: A-BR-102-085