GI-CT: Genotyping Guided Individualized Treatment of Clopidogrel and Ticagrelor in ACS

Sponsor

Chinese PLA General Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT02048228

Collaborator

(none)

200

Enrollment

Location

Arms

Duration (Months)

9.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Clopidogrel, in addition to aspirin, is the cornerstone of therapy in patients suffering from Acute coronary syndrome. However, the platelet inhibitory response to clopidogrel varies substantially among individuals. Several loss-of-function polymorphisms have been identified that may influence clinical outcome in patients presenting with acute coronary syndromes (ACS) who are treated with clopidogrel. However their contribution to high on-treatment platelet reactivity (HPR) in clopidogrel treated Chinese patients is less known. As far as we know, ticagrelor is not dependent on gene-based metabolic activation and demonstrated greater clinical efficacy than clopidogrel in a recent secondary prevention trial. we will conduct an interventional study to compare the antiplatelet efficiency between clopidogrel and ticagrelor by the guidance of CYP450 2C192 (CYP2C192) , using Taqman genotyping method.

Condition or Disease	Intervention/Treatment	Phase
CLOPIDOGREL, POOR METABOLISM of (Disorder)	Drug: genotyping guided therapy Ticagrelor, Clopidogrel Drug: standard therapy clopidogrel	Phase 2/Phase 3

Detailed Description

Mounting evidence suggests a crucial role for the loss-of-function CYP2C192 genetic variant. Carriers of CYP2C192 allele were at 30% higher risk for major adverse clinical events compared to non-carriers. CYP2C19*2 alone was also associated with increased mortality and stent thrombosis. These findings led the American Food and Drug Administration to issue a boxed warning for clopidogrel stating that poor metabolizers may not receive the full benefit of the drug. Thus, routine genotyping in the context of dual anti-platelet therapy is necessary.

Individual dual anti-platelet treatment is feasible to give the presence of treatment alternatives such as ticagrelor that is not dependent on gene-based metabolic activation and demonstrated greater clinical efficacy than clopidogrel. Individualized administration of ticagrelor may have the potential to successfully minimize adverse ischemic events.

200 patients undergoing percutaneous coronary intervention (PCI) for treatment of non-ST-elevation acute coronary syndrome or stable coronary artery disease will be eligible for enrollment. Patients will be randomly assigned to a strategy of genotyping(using Taqman genotyping method) or standard treatment . CYP2C19*2 carriers will be given 90 mg ticagrelor twice daily, and non-carriers and patients in the standard treatment group will be given 75 mg clopidogrel daily. At the end of the 5 day antiplatelet treatment, efficacy of the treatment strategies will be evaluated using light transmittance aggregometry (LTA) method.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Study of Clopidogrel and Ticagrelor Anti-Platelet Treatment Using an Individualized Strategy Based on Genotyping in Chinese ACS Patients

Study Start Date :

Oct 1, 2014

Anticipated Primary Completion Date :

Mar 1, 2016

Anticipated Study Completion Date :

Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: genotyping guided therapy Patients randomized to the genotyping guided therapy arm will have their CYP2C192 carrier status determined at the time before antiplatelet therapy with subsequent alteration in antiplatelet therapy for 2 carriers.CYP2C19*2 carriers will be given 90 mg ticagrelor twice daily, and non-carriers will be given 75 mg clopidogrel daily.	Drug: genotyping guided therapy Ticagrelor, Clopidogrel CYP2C19*2 carriers will be given 90 mg ticagrelor twice daily, and non-carriers and patients in the standard treatment group will be given 75 mg clopidogrel daily. Other Names: Ticagrelor Clopidogrel
Active Comparator: Standard Therapy Patients randomized to the Standard Therapy arm will not undergo genotyping. All patients will be administrated with clopidogrel 75 mg daily for 5 consecutive days.	Drug: standard therapy clopidogrel All patients will be administrated with clopidogrel 75 mg daily for 5 consecutive days. Other Names: clopidogrel

Arm

Intervention/Treatment

Experimental: genotyping guided therapy

Patients randomized to the genotyping guided therapy arm will have their CYP2C19*2 carrier status determined at the time before antiplatelet therapy with subsequent alteration in antiplatelet therapy for *2 carriers.CYP2C19*2 carriers will be given 90 mg ticagrelor twice daily, and non-carriers will be given 75 mg clopidogrel daily.

Drug: genotyping guided therapy Ticagrelor, Clopidogrel

CYP2C19*2 carriers will be given 90 mg ticagrelor twice daily, and non-carriers and patients in the standard treatment group will be given 75 mg clopidogrel daily.

Other Names:

Ticagrelor

Clopidogrel

Active Comparator: Standard Therapy

Patients randomized to the Standard Therapy arm will not undergo genotyping. All patients will be administrated with clopidogrel 75 mg daily for 5 consecutive days.

Drug: standard therapy clopidogrel

All patients will be administrated with clopidogrel 75 mg daily for 5 consecutive days.

Other Names:

clopidogrel

Outcome Measures

Primary Outcome Measures

Clopidogrel response status as measured by the LTA assay in CYP2C19*2 carriers. [Day 5 of enrollment]
The primary endpoint is the proportion of CYP2C19*2 carriers with a platelet aggregation more than 59% after 5 days of antiplatelet therapy.The deﬁnition of high on-treatment platelet reactivity is derived from previous studies that had identiﬁed platelet aggregation more than 59% as optimum cutoff values for prediction of increased risk of major adverse cardiovascular events in Chinese patients.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

The diagnosis of ACS including unstable angina (UA),non-ST elevation myocardial infarction(NSTEMI),and ST-elevation MI (STEMI) is according to the American Heart Association/American College of Cardiology (AHA/ACC) criteria

Exclusion Criteria:

known contraindication to dual anti-platelet therapy, history of chronic inflammatory disease, steroidal and non-steroidal anti-inflammatory drugs use, previous administration of antiplatelet drugs within 1 month before coronary artery angiography, illicit drug abuse, significant bleeding, cerebrovascular event within 3months, and/or major surgery within 4 weeks.