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

NCT ID: NCT02578537

Last Updated: 2015-12-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2016-07-31

Brief 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.

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.

Conditions

Non ST Segment Elevation Acute Coronary Syndrome; Chronic Kidney Disease

Keywords

Ticagrelor; Pharmacokinetics; NSTE-ACS; CKD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Ticagrelor group

ticagrelor 180mg loading, followed by 90mg bid for 30 days

Group Type: EXPERIMENTAL

Ticagrelor

Intervention Type: DRUG

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 group

clopidogrel 600mg loading, followed by 75mg/d for 30 days

Group Type: ACTIVE_COMPARATOR

Clopidogrel

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Brilinta; Plavix

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shenyang Northern Hospital

OTHER

Sponsor Role: lead

Responsible Party

Han Yaling

Dr

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yaling Han, MD

Role: PRINCIPAL_INVESTIGATOR

General Hospital of Shenyang Military Region

Locations

Shenyang Northern Hospital

Shenyang, Liaoning, China

Site Status: RECRUITING

Countries

China

Central Contacts

Heyang Wang, MD

Role: CONTACT

Phone: 86-024-28897309

Email: whysmmu@163.com

Facility Contacts

Yaling Han, MD,PHD

Role: primary

Yi Li, MD

Role: backup

References

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.

Reference Type: DERIVED

PMID: 35224730 (View on PubMed)

Other Identifiers

ESR-14-10607

Identifier Type: -

Identifier Source: org_study_id