Pharmacogenomics of Anti-platelet Intervention-2 (PAPI-2) Study (PAPI-2)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01452152|
Recruitment Status : Terminated (Terminated by study sponsor.)
First Posted : October 14, 2011
Results First Posted : June 28, 2016
Last Update Posted : March 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Cardiovascular Diseases Acute Coronary Syndrome||Drug: clopidogrel Drug: prasugrel||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||9 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pharmacogenomics of Anti-platelet Intervention-2 (PAPI-2) Study: A Prospective, Multicenter, Randomized Trial of Genotype-directed (G-D)Versus Standard of Care (SOC)Anti-platelet Therapy|
|Study Start Date :||February 2012|
|Actual Primary Completion Date :||July 2013|
|Actual Study Completion Date :||July 2013|
Experimental: Genotype-directed, clopidogrel
Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 extensive and ultrarapid metabolizers will receive clopidogrel.
clopidogrel 75 mg/day plus aspirin 81-162 mg/day for one year
Other Name: Plavix
Experimental: Genotype-directed, prasugrel
Participants randomized to the G-D group will have CYP2C19 genotype analysis performed. CYP2C19 intermediate and poor metabolizers will receive prasugrel.
Prasugrel 5-10 mg/day plus aspirin 81-162 mg/day for one year
Other Name: Effient
No Intervention: Standard of Care
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.
- Occurrence of Post-randomization Cardiovascular Events [ Time Frame: One year ]Cardiovascular events include non-fatal myocardial infarction, non-fatal stroke, definite or probable stent thrombosis (ARC definition) and death secondary to any cardiovascular cause.
- Occurrence of Bleeding Events [ Time Frame: One year ]Bleeding events will classified by the Bleeding Academic Research Consortium definition. The number of bleeding events will be tabulated.
- Post-treatment Platelet Aggregation [ Time Frame: 10 days ]Platelet aggregation will be performed on a subset of subjects using VerifyNow P2Y12 which measures platelet reactivity due to the effect of a P2Y12. Values less than 180 P2Y12 Reaction Units (PRU) suggest evidence of a P2Y12 inhibitor effect. Platelet aggregation studies are optional and will not be used to modulate antiplatelet therapy.
- Health Care Resource Utilization and Cost-effectiveness [ Time Frame: One year ]
- Occurrence of Adverse Events [ Time Frame: One year ]The number of subjects reporting any AEs will be tabulated.
- Composite of All-cause Death, Myocardial Infarction (MI), Stroke and Repeat Revascularization [ Time Frame: One year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01452152
|United States, Delaware|
|Christiana Care Health System|
|Newark, Delaware, United States, 19718|
|United States, Maryland|
|University of Maryland School of Medicine|
|Baltimore, Maryland, United States, 21201|
|Sinai Center for Thrombosis Research|
|Baltimore, Maryland, United States, 21209|
|The Johns Hopkins University School of Medicine|
|Baltimore, Maryland, United States, 21287|
|United States, Pennsylvania|
|Geisinger Health System|
|Danville, Pennsylvania, United States, 17822|
|Principal Investigator:||Alan R Shuldiner, M.D.||University of Maryland|