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| FOR IMMEDIATE RELEASE
New Study to Examine Genotyping and Platelet Function Testing at Point-of-Care to Personalize Anti-Platelet Therapy and Improve Patient Outcomes Paul A. Gurbel, M.D. of the Center for Thrombosis Research at Sinai Hospital Will be first in the U.S. to Use
A new study by the Center for Thrombosis Research at Sinai Hospital in Baltimore, MD will examine the utility of point-of-care genetic and platelet function testing to identify patients at risk for a cardiac event after coronary stenting. Therapy will be altered based on the testing results with the goal of improving patient outcomes. Under the direction of Paul A. Gurbel, MD, Director of the Sinai Center for Thrombosis Research, 1,500 patients will be enrolled in the study entitled, "Thrombocyte Activity Reassessment and GEnoTyping for PCI (TARGET-PCI)” that began July 15, 2010. The study should be completed by late 2012.
Gurbel and his team will be the first in the United States (and perhaps the world) to use the Verigene System (Nanosphere, Nasdaq:NSPH Northbrook, IL) point-of-care assay (Verigene IUO CBS Assay [CYP219] for investigational use only*) to detect the specific genotypes carried by 30 percent of the population that have previously been associated with clopidogrel (Plavix, Sanofi Aventis) nonresponsiveness and subsequent poorer outcomes in patients treated with coronary stents. Upon regulatory approval of this specific Verigene System test by the FDA, Gurbel and his team plan to make point-of-care genetic and platelet function testing available to all cardiac patients at the Heart Center at Sinai, another first.
In addition, the study will employ another point-of-care assay, VerifyNow P2Y12 (Accumetrics, San Diego) to determine each patient's individual antiplatelet (phenotypic) response to clopidogrel. The results of these two tests will be known within hours as opposed to days or weeks when determined by conventional methods.
The study was spurred by growing data from Gurbel's and other researchers' findings that continue to present strong arguments against the "one-size-fits-all” approach to anti-platelet therapy
recommended by current guidelines. At one end of the spectrum, patients with high platelet reactivity have a marked increase in recurrent ischemic event occurrence after coronary stenting, whereas patients with very low platelet reactivity may have bleeding due to excessive platelet inhibition.
Another impetus for the study was the U.S. Food and Drug Administration's mandate in March 2010 that a warning be added to Plavix labeling stating the drug can be less effective in people who carry specific genotypes and cannot effectively metabolize the drug.
"The FDA's black box warning has left clinicians in a conundrum since the pharmacogenetic testing that reveals a patients' genetic profile is not readily available," added Gurbel. "This study will provide the missing piece to that puzzle by substantiating the importance of point-of care genetic and platelet response testing in PCI patients. Our study will determine whether this type of testing can be administered and utilized in a relatively short amount of time to truly personalize antiplatelet therapy."
About the Study
Thrombocyte Activity Reassessment and GenoTyping for PCI (TARGET-PCI) is an investigator-initiated study developed by Gurbel and his team that will use 2C19 genotyping and platelet function testing to personalize antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI). The comparator group will receive standard post-PCI therapy at the discretion of the practicing cardiologist. In the guided therapy arm, prasugrel (Effient, Eli Lilly and Company/ Daiichi Sankyo, Inc.) will be used to treat patients with the phenotype or genotypes associated with increased post-PCI ischemic risk.
1. Provide evidence that point-of-care genetic and platelet function testing can be successfully used to identify patients at ischemic risk and alter antiplatelet therapy to improve outcomes.
2. Provide insight on the long-term stability of platelet function. By serial measurements of platelet function (2 weeks, 3 and 6 months post-PCI), the platelet reactivity phenotype will be characterized closer to the time of both ischemic and bleeding events. Serial measurements have been performed infrequently in earlier studies. The latter knowledge may be important for future studies where antiplatelet strategies may be modified dynamically in selected patients to reduce the occurrence of adverse clinical events (bleeding and ischemia).
Brief Study Design Overview:
TARGET-PCI is a prospective, multi-center, randomized trial including 1,500 patients undergoing non-emergent PCI with drug eluting stents. Patients with stenotic lesions in either native coronary arteries or coronary artery bypass grafts and no contraindication to prolonged dual antiplatelet therapy (=1 year) are eligible for the study. Patients will be randomized (1:1 ratio) to guided or standard (non-guided) antiplatelet therapy. In the "guided” arm, initial therapy will be determined by VerifyNow for patients already on clopidogrel therapy prior to presentation for PCI. The majority of patients (those not on chronic clopidogrel therapy) will have initial therapy determined by the Verigene CYP2C19 genotyping assay. VerifyNow testing will occur at 2 weeks, 3 months, and 6 months for patients in the guided therapy group. Patients triaged to clopidogrel therapy based on genotyping who have high platelet reactivity at 2 weeks or 3 months will be switched to prasugrel therapy. The primary endpoint is the composite of cardiovascular death, non-fatal myocardial infarction, stroke and urgent target vessel revascularization at 6 months post-PCI. After completing 6 months of the study treatment period, further antiplatelet therapy will be at the physician's discretion.
About Sinai Hospital of Baltimore
Sinai Hospital of Baltimore is part of LifeBridge Health, one of Baltimore's largest health organizations that includes Northwest Hospital, Levindale Hebrew Geriatric Center and Hospital, and Courtland Gardens Nursing & Rehabilitation Center. For more information, visit www.lifebridgehealth.org.
*For Investigational Use Only (IUO) Studies: The investigator acknowledges and understands that the Verigene® IUO CBS assay (CYP2C19SP) has not been reviewed by or approved by the FDA and is classified as a "For Investigational Use Only” (IUO) device. This label pertains to an in vitro diagnostic device being shipped or delivered for product testing prior to full commercial marketing (e.g., for use on specimens derived from humans to compare the usefulness of the product with other products or procedures which are in current use or recognized as useful). All assay labeling must bear the statement, prominently placed: "For Investigational Use Only. The performance characteristics of this product have not been established." The Investigator and the Sponsor (Nanosphere) must follow the regulations that are detailed in 21 CFR 812 of the Code of Federal Regulations, including IRB review/approval and other pertinent IDE regulations. If the reviewing IRB finds that the investigational device is a "significant risk device,” the IDE application must be submitted to the FDA for review and approval.