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

Chronic Kidney Disease Clinical Trial

— OPT-CKD  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02578537
• Other study ID #: ESR-14-10607
• Status: Recruiting
• Phase: Phase 4
• First received: October 15, 2015
• Last updated: December 10, 2015
• Start date: October 2015
• Est. completion date: July 2016

Study information

• Verified date: December 2015
• Source: Shenyang Northern Hospital
• Contact: Heyang Wang, MD
• Phone: 86-024-28897309
• Email: whysmmu[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: July 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Chronic Kidney Disease
• Kidney Diseases
• Non ST Segment Elevation Acute Coronary Syndrome
• Renal Insufficiency, Chronic
• Syndrome

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Shenyang Northern Hospital	Shenyang	Liaoning

Sponsors (1)

Lead Sponsor	Collaborator
Shenyang Northern Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PRU assayed by VerifyNow		30 days after loading does of study drug
Secondary	PRU assayed by VerifyNow		at the time of pre-dose, and 2 hours, 8 hours, and 24 hours after loading dose of study durg.
Secondary	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
Secondary	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.
Secondary	Plasma concentration of ticagrelor and clopidogrel		at 2 hours, 8 hours, and 24 hours after loading dose of study durg.
Secondary	Bleeding events	by BARC classification	30 days after loading does of study drug