COmparison of the Pharmacodynamics and Pharmacokinetics Ticagrelor Versus Clopidogrel in Patients With CKD and NSTE-ACS (OPT-CKD)

COmparison of the Pharmacodynamics and Pharmacokinetics of Ticagrelor Versus Clopidogrel in Patients With Chronic Kidney Disease and Non-ST-Elevation Acute Coronary Syndromes(OPT-CKD Trial)

Ticagrelor, a new P2Y12 receptor antagonist, achieve faster, consistent and higher platelet inhibition than clopidogrel, which was considered more noticeable in patients with ACS combining chronic kidney disease(CKD). Nonetheless, the pharmacokinetic properties of ticagrelor in the patients with CKD and NSTE-ACS has not been thoroughly studied. This study was designed to provide PK and PD data of ticagrelor compared with clopidogrel, in order to estimate that ticagrelor is superior to clopidogrel in getting better inhibition of platelet in patients with CKD and NSTE-ACS. P2Y12 inhibitor naïve patients with CKD (eGFR < 60 ml/min/1.73m2 ) and NSTE-ACS will be enrolled in this single-center, prospective, randomized, parallel-control study and randomly assigned in a one-to-one ratio to receive ticagrelor or clopidogrel on top of chronic aspirin treatment. The primary endpoint was the PRU by Verify Now at 30 days after loading dose.

Study Overview

• Status: Unknown
• Conditions: Chronic Kidney Disease; Non ST Segment Elevation Acute Coronary Syndrome
• Intervention / Treatment: Drug: Ticagrelor; Drug: Clopidogrel

Detailed Description

Dual antiplatelet therapy with aspirin and clopidogrel has become the standard care in patients with acute coronary syndrome (ACS). However, clopidogrel is being questioned for its insufficient platelet inhibition and residual platelet reactivity, especially in patients with impaired renal function. Ticagrelor, a new P2Y12 receptor antagonist, achieve faster, consistent and higher platelet inhibition than clopidogrel, which was more noticeable in patients with ACS combining chronic kidney disease(CKD). Nonetheless, the pharmacokinetic properties of ticagrelor in the patients with CKD and NSTE-ACS, to the best of the investigators' knowledge, has not been thoroughly studied. This study was designed to provide PK and PD data of ticagrelor compared with clopidogrel, in order to estimate that ticagrelor is superior to clopidogrel in getting better inhibition of platelet in patients with CKD and NSTE-ACS. The potential hypothesis is to evaluate the correlation of platelet inhibition and renal function and CYP2C19 gene type in patients treated by ticagrelor and clopidogrel. P2Y12 inhibitor naïve patients with CKD (eGFR < 60 ml/min/1.73m2 ) and NSTE-ACS will be enrolled in this single-center, prospective, randomized, parallel study and randomly assigned in a one-to-one ratio to receive ticagrelor or clopidogrel on top of chronic aspirin treatment. The primary endpoint was the PRU by Verify Now at 30 days after loading dose.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Heyang Wang, MD; Phone Number: 86-024-28897309; Email: whysmmu@163.com

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110016
      • Recruiting
      • Shenyang Northern Hospital
      • Contact: Yaling Han, MD,PHD; Phone Number: 86-024-28856123; Email: hanyaling@263.net
      • Contact: Yi Li, MD; Phone Number: 86-024-28897309; Email: doctorliyi@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• P2Y12 inhibitor naïve patients presenting with NSTE-ACS (unstable angina or non-ST segment elevation myocardial infarction).
• Males and non-pregnant females > 18 years of age.
• eGFR<60 ml/min/1.73m2 (MRDR formula).
• With planned percutaneous coronary intervention(PCI will be performed over 24 hours after loading dose).
• Written informed consent provided.Provision of informed consent prior to any study specific procedures.

Exclusion Criteria:

• Cardiogenic shock.
• Thrombolytic therapy administered before randomization.
• Active bleeding or bleeding predisposition, including the retinal or vitreous hemorrhage , gastrointestinal or urinary tract hemorrhage , history of intracranial haemorrhage or cerebral infarction .
• Hypersensitivity to ticagrelor or any excipients.
• Deep puncture or major surgery within 1 month.
• Untreated or uncontrolled hypertension with blood pressure >180/110 mmHg.
• Known hemoglobin <10 g/dL or platelet count <100 × 109/L.
• Known moderate or severe hepatic impairment.
• Known aminotransferase level >3x the upper limit of normal.
• Known allergy to any of the study drugs or devices (aspirin, clopidogrel, ticagrelor stainless steel, contrast agents, etc.).
• Pregnancy or lactation.
• Any condition which might interfere with study compliance, or otherwise unsuitable for study participation as judged by the investigators.
• Unwilling or unable to get repeat platelet assay or clinical follow-up.
• Unwilling or unable to provide written informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ticagrelor group; ticagrelor 180mg loading, followed by 90mg bid for 30 days	Drug: Ticagrelor; Ticagrelor group:all patients receive ticagrelor (180 mg loading dose, then 90 mg twice daily followed for 30 days). All patients were given aspirin 100 mg per day unless they were intolerant. For those not previously given aspirin, a loading dose of 300 mg was preferred.; Other Names: Brilinta
Active Comparator: Clopidogrel group; clopidogrel 600mg loading, followed by 75mg/d for 30 days	Drug: Clopidogrel; Clopidogrel group:all patients receive clopidogrel (600 mg loading dose, then 75 mg once daily followed for 30 days). All patients were given aspirin 100 mg per day unless they were intolerant. For those not previously given aspirin, a loading dose of 300 mg was preferred.; Other Names: Plavix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PRU assayed by VerifyNow	30 days after loading does of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PRU assayed by VerifyNow		at the time of pre-dose, and 2 hours, 8 hours, and 24 hours after loading dose of study durg.
Index of Platelet activity	calculated by the change of the P2Y12 reaction units (PRU) from baseline	at the time of 2 hours, 8 hours, and 24 hours after loading dose of study drug
Rate of high on-treatment platelet reactivity (HPR)		at the time of pre-dose, and 2 hours, 8 hours, 24 hours and 30 days after loading dose of study durg.
Plasma concentration of ticagrelor and clopidogrel		at 2 hours, 8 hours, and 24 hours after loading dose of study durg.
Bleeding events	by BARC classification	30 days after loading does of study drug

Collaborators and Investigators

• Sponsor: Shenyang Northern Hospital
• Investigators: Principal Investigator: Yaling Han, MD, General Hospital of Shenyang Military Region

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: October 1, 2015
• Primary Completion (Anticipated): April 1, 2016
• Study Completion (Anticipated): July 1, 2016

Study Registration Dates

• First Submitted: October 15, 2015
• First Submitted That Met QC Criteria: October 16, 2015
• First Posted (Estimate): October 19, 2015

Study Record Updates

• Last Update Posted (Estimate): December 11, 2015
• Last Update Submitted That Met QC Criteria: December 10, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Ticagrelor; Pharmacokinetics; CKD; NSTE-ACS
• 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; 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: ESR-14-10607