Clinical trial NCT01452152
Conditions: Cardiovascular Diseases Acute Coronary Syndrome
Keywords: Pharmacogenomics Platelet Aggregation Inhibitors
Sponsor: University of Maryland, Baltimore
Start date: 2012-02-01; Completion date: 2013-07-01
Enrollment: 9 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
It is standard treatment to take anti-platelet medication after cardiac catheterization and stent placement to help prevent the formation of blood clots that may cause heart attack or stroke. The most commonly used anti-platelet medicine is clopidogrel (Plavix®). However, researchers have found that people vary in their response to clopidogrel, in part because of differences in their genes. Prasugrel (Effient®)is another anti-platelet medication used to prevent clots. The genetic differences that affect clopidogrel response do not affect prasugrel response. Recently, the FDA added a warning to the label of clopidogrel to notify doctors and patients with certain genetic differences may not get the full benefit from clopidogrel. Despite this, genetic testing for these variations is not usually done in standard medical practice. The purpose of this study is to see if patients with certain gene differences have fewer major cardiac events after stent placement if they are given anti-platelet therapy guided by their individual genetic type compared to standard anti-platelet therapy.

Detailed description:
Over a three-year period, a total of 7,200 patients undergoing percutaneous coronary intervention (PCI) in whom dual anti-platelet therapy is indicated for at least one year and meet the eligibility criteria, will be recruited from five or more clinical sites. Patients presenting to the cardiac clinics, emergency departments, catheterization laboratories, and other acute care units (e.g. CCU) who will have coronary angiography or have had angiography and PCI will be offered participation. Following informed consent, patients will have baseline data and specimens collected, and eligibility confirmed. Patients will be randomized in equal numbers to the G-D arm or SOC arm. Immediately following randomization, a blood sample from patients assigned to the G-D arm will be sent for CYP2C19 genotype analysis. Upon receipt of CYP2C19 genotype results, patients randomized to the G-D arm with the CYP2C19 \*1/\*1 genotype (extensive metabolizers) and \*1/\*17, and \*17/\*17 genotypes (ultrarapid metabolizers) will receive clopidogrel 75 mg/day plus aspirin 81-162 mg/day (group a). Those with \*1/\*2, \*1/\*3, \*2/\*17, and \*3/\*17 genotypes (intermediate metabolizers) and those with \*2/\*2, \*2/\*3, and \*3/\*3 genotypes (poor metabolizers) will receive prasugrel 5-10 mg/day plus aspirin 81-162 mg/day (group b). Patients randomized to the SOC arm will not be genotyped prospectively. They will receive dual anti-platelet therapy guided by the judgment of their treating physician according to standard medical practice irrespective of genotype (group c). Optionally, a subgroup of patients will return at 10 days after the randomization visit for platelet aggregation studies.

If our hypothesis is correct, i.e., that in intermediate and poor metabolizers, G-D anti-platelet therapy results in fewer cardiovascular events and has less or equivalent bleeding complications compared to SOC therapy, and is cost effective, this prospective randomized clinical trial will provide the evidence base to implement genotype-directed anti-platelet treatment algorithms broadly into clinical practice.

Arms: arm 1: Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 extensive and ultrarapid metabolizers will receive clopidogrel. arm 2: Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 intermediate and poor metabolizers will receive prasugrel. arm 3: Participants randomized to the SOC group will not have CYP2C19 genotype analysis performed. They will receive dual anti-platelet therapy guided by the judgment of their treating physician according to standard medical practice irrespective of genotype.
Interventions: intervention 1: clopidogrel intervention 2: prasugrel
Intervention descriptions: intervention 1: clopidogrel 75 mg/day plus aspirin 81-162 mg/day for one year intervention 2: Prasugrel 5-10 mg/day plus aspirin 81-162 mg/day for one year

Protocol documents: