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

• ClinicalTrials.gov Identifier: NCT02459288
• Recruitment Status: Unknown
• First Posted: June 2, 2015
• Last Update Posted: June 2, 2015
• Sponsor: Ping-Yen Liu
• Information provided by (Responsible Party): Ping-Yen Liu, National Cheng-Kung University Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Coronary Syndrome; Chronic Kidney Disease; End-Stage Renal Disease	Drug: Clopidogrel first; Drug: Ticagrelor first	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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.
• Study Start Date: January 2014
• Estimated Primary Completion Date: December 2015
• Estimated Study Completion Date: December 2015

Arms and Interventions

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 Name: 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 Name: T-C

Outcome Measures

Primary Outcome Measures :

1. platelet VerifyNow inhibition rate and Platelet Residual Unit (PRU) values changes [ Time Frame: baseline, 2 weeks and 4 weeks later (compare cross over effect) ]

Secondary Outcome Measures :

1. Major bleeding events [ Time Frame: 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)

Other Outcome Measures:

1. Myocardial infarction [ Time Frame: 1 year ]
2. emergent condition with hospitalization need [ Time Frame: 30 days ]
   Number of subjects with an emergent condition that required hospitalization

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Ping-Yen Liu, MD, PhD.; +88662353535 ext 4602; larry@mail.ncku.edu.tw

Locations

Taiwan

Department of Internal Medicine, National Cheng Kung University Hospital; Recruiting

Tainan, Taiwan, 704

Contact: Ping-Yen Liu, MD, PhD. +88662353535 ext 4602 larry@mail.ncku.edu.tw

Sponsors and Collaborators

Ping-Yen Liu

Investigators

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

More Information

• Responsible Party: Ping-Yen Liu, Attending Physician, National Cheng-Kung University Hospital
• ClinicalTrials.gov Identifier: NCT02459288
• Other Study ID Numbers: A-BR-102-085
• First Posted: June 2, 2015
• Last Update Posted: June 2, 2015
• Last Verified: May 2015

Keywords provided by Ping-Yen Liu, National Cheng-Kung University Hospital:

Acute coronary syndrome; Chronic kidney disease; End-Stage Renal Disease; eGFR; Ticagrelor; Clopidogrel

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Acute Coronary Syndrome; Syndrome; Disease; Pathologic Processes; Urologic Diseases; Renal Insufficiency; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Clopidogrel; Ticagrelor; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs