Pharmacogenomics of Anti-platelet Intervention-2 (PAPI-2) Study
Condition: Cardiovascular Diseases; Acute Coronary Syndrome
MeSH terms: Cardiovascular Diseases; Acute Coronary Syndrome
Intervention: clopidogrel; prasugrel
Intervention description: clopidogrel 75 mg/day plus aspirin 81-162 mg/day for one year; Prasugrel 5-10 mg/day plus aspirin 81-162 mg/day for one year
Intervention MeSH terms: Clopidogrel; Prasugrel Hydrochloride
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 20 Years
Maximum age: 74 Years
Healthy volunteers: No
Keywords: Pharmacogenomics; Platelet Aggregation Inhibitors

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males or non-pregnant females between the ages of 20 and 74 years, inclusive

          -  Not more than four days post-PCI (percutaneous coronary intervention) with placement
             of one or more drug eluting or bare metal stents

          -  One or more stent(s) delivered with final TIMI 3 flow (thrombolysis in myocardial
             infarction grade 3) in the stented vessel(s)

          -  Must have evidence of one of the following:

               1. Three vessel disease;

               2. Two vessel disease with one of the following: estimated creatinine clearance <60,
                  prior myocardial infarction, diabetes mellitus on treatment, peripheral artery
                  disease, cerebrovascular disease, bifurcation stent, overlapping stents, or total
                  stent deployment length > 40 mm in length;

               3. Single vessel disease with two of the following: estimated creatinine clearance
                  <60, prior myocardial infarction, diabetes mellitus on treatment, peripheral
                  artery disease, cerebrovascular disease, bifurcating stenting, overlapping
                  stents, or total stent deployment length > 40 mm in length.

          -  Patients with acute MI (myocardial infarction) preceding the PCI must have CK-MB
             (bound combination of creatine kinase M and creatine kinase B) value lower than the
             prior value, before randomization

          -  Patients with peri-procedural MI, defined by CK-MB three times greater than upper
             reference limit (URL), must have CK-MB value lower than the prior value, before
             randomization. Peri-procedural MI will be screened per clinical suspicion.

          -  Have an indication for one year of dual anti-platelet therapy with a P2Y12 inhibitor
             and aspirin

          -  Agreement of the treating physician to prescribe anti-platelet therapy according to
             randomization and study dosing algorithm

          -  Ability to understand and comply with planned study procedures

          -  Provide written informed consent prior to study entry

          -  Agrees to authorize the collection and release of his/her medical information for the
             duration of the trial or until the subject withdraws

        Exclusion Criteria:

          -  History of a gastrointestinal bleed within three months or a major, life threatening
             bleeding event (e.g., sub-arachnoid or intracranial hemorrhage)

          -  Active pathological bleeding (e.g. GI bleeding)

          -  History of bleeding diathesis or coagulopathy

          -  History of stroke or transient ischemic attack (TIA)

          -  Non-cardiac surgery within the prior 3 months

          -  Planned cardiac or non-cardiac surgery within the next 12 months

          -  CYP2C19 genotype already known to subject or research team from prior genetic testing

          -  Post-PCI CABG (coronary artery bypass graft) before randomization

          -  Planned warfarin or dabigatran therapy any time during the study period

          -  Known allergy to aspirin, clopidogrel or prasugrel

          -  Platelet count <100,000/mm3

          -  Hematocrit < 25%

          -  Pregnancy

          -  Concurrent enrollment in another trial that involves an investigational stent,
             antithrombotic or anti-platelet agent

          -  Any condition that would, in the opinion of the site investigator, place them at an
             unacceptable risk or render them unable to meet the requirements of the protocol

          -  Any subject, in the opinion of the investigator, not expected to tolerate or be
             adherent with one year of dual antiplatelet therapy