ORLANDO, Fla., Nov. 5 /PRNewswire-FirstCall/ -- Schering-Plough Corporation and The Sinai Center for Thrombosis Research at Sinai Hospital of Baltimore today announced results of the recently completed CLEAR PLATELETS 2 (Clopidogrel Loading with Eptifibatide to Arrest the Reactivity of Platelets) study, showing that INTEGRILIN(R), a potent glycoprotein (GP) IIb- IIIa inhibitor, significantly inhibited platelet aggregation when added to bivalirudin, compared to bivalirudin alone, in patients undergoing elective coronary stenting. Results were presented at the American Heart Association Scientific Sessions in Orlando, FL.
CLEAR PLATELETS 2, designed to evaluate the effects of the addition of INTEGRILIN(R) to an antithrombotic regimen of aspirin, clopidogrel and bivalirudin in elective PCI patients, demonstrated that when added to bivalirudin, INTEGRILIN(R) significantly decreased platelet aggregation in response to multiple stimuli, thereby producing increased platelet inhibition. Results were statistically significant for all measurements of platelet aggregation induced by multiple agonists.
“The results reflect the importance of a GP IIb-IIIa inhibitor in reducing platelet aggregation,” said Paul Gurbel, MD, Director of The Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore; Associate Professor at Johns Hopkins University, and principal investigator for the CLEAR PLATELETS 2 study. “This pharmacodynamic study supports the role of inhibition of platelet aggregation in patients undergoing elective coronary stenting,” added Dr. Gurbel.
About CLEAR PLATELETS 2
CLEAR PLATELETS 2 was a randomized two-center, open label study enrolling 200 patients undergoing elective PCI with stenting who were given high-dose clopidogrel (600 mg) in the absence of chronic clopidogrel therapy and aspirin (325 mg) and then randomized to either a bivalirudin alone (n=102) or bivalirudin + INTEGRILIN(R) (n=98). The primary outcome of the study was to compare the antiplatelet effects of bivalirudin vs. bivalirudin plus INTEGRILIN(R) in patients being treated with clopidogrel and aspirin at the time of elective percutaneous intervention. Secondary outcomes were the release of markers of myocardial necrosis, inflammatory markers and in- hospital, 30-day, and 1-year clinical outcomes.
All patients post-stenting received standard antiplatelet treatment (75 mg clopidogrel and 325 mg aspirin daily). Patients had serial assessment of platelet reactivity, myocardial necrosis markers, and inflammatory markers at baseline, 2 hours, 8 hours, and 18-24 hours post-stenting. Blood work was processed at The Sinai Center for Thrombosis Research and the University of Oklahoma Health Science Center. Platelet reactivity was measured by aggregometry and flow cytometry. Thrombelastography measured the characteristics of maximum platelet-fibrin clot strength and time to initial platelet-clot formation. Clinical outcomes were recorded using a standard case report form. Patients were followed to 30 days, and will be further followed to one year. In the secondary outcome of 30-day clinical events, the rate of periprocedural myocardial infarction in the bivalirudin plus INTEGRILIN(R) treatment arm was 2% vs. 9% in the bivalirudin alone treatment arm. Statistical significance of these findings has not yet been confirmed.
Bivalirudin plus INTEGRILIN(R) compared to bivalirudin alone produced greater relative inhibition of platelet aggregation induced by 5 or 20 uM ADP, 15 or 25 uM TRAP, or collagen (p<0.01 for all). Platelet reactivity and maximum platelet-fibrin clot strength were higher in patients with myocardial infarction.
This is the first study in PCI patients to demonstrate the inhibitory effect of INTEGRILIN(R) on the physical characteristics of a platelet-fibrin clot.
CLEAR PLATELETS 2 builds on the results of the original CLEAR PLATELETS study, which demonstrated that adding INTEGRILIN(R) to a 300-mg loading dose of clopidogrel produced greater platelet inhibition and reduced cardiac biomarkers than clopidogrel alone in patients undergoing elective stenting. Data from this study were presented at the 2004 American Heart Association Scientific Sessions. CLEAR PLATELETS 2 was an investigator-initiated study funded by Schering-Plough.
About Sinai Hospital of Baltimore
Sinai Hospital of Baltimore is a member of LifeBridge Health, a regional health organization, which includes Northwest Hospital Center, Levindale Hebrew Geriatric Center and Hospital, Jewish Convalescent & Nursing Home and related subsidiaries and affiliates.
About INTEGRILIN(R) Injection
INTEGRILIN(R) is indicated for the treatment of patients with acute coronary syndrome (unstable angina/non-ST-segment-elevation myocardial infarction), including patients who are to be managed medically and those undergoing percutaneous coronary intervention (PCI). It is also indicated in the United States for the treatment of patients at time of PCI, including in patients undergoing intracoronary stenting.
INTEGRILIN(R) is contraindicated in patients with a history of bleeding diathesis, or evidence of abnormal bleeding within the previous 30 days; severe hypertension (systolic blood pressure greater than 200 mm Hg or diastolic blood pressure greater than 110 mm Hg) not adequately controlled on antihypertensive therapy; major surgery within the preceding six weeks; history of stroke within 30 days, or any history of hemorrhagic stroke; current or planned administration of another parenteral GP IIb-IIIa inhibitor; dependency on renal dialysis; or known hypersensitivity to any component of the product.
Bleeding is the most common complication encountered during INTEGRILIN(R) therapy. The majority of excess major bleeding events were localized at the femoral artery access site. Oropharyngeal, genitourinary, gastrointestinal and retroperitoneal bleeding were also seen more commonly with INTEGRILIN(R) compared to placebo; INTEGRILIN(R) is associated with an increase in major and minor bleeding at the site of arterial sheath placement; special care should be employed to minimize the risk of bleeding among these patients; if bleeding cannot be controlled with pressure, infusion of INTEGRILIN(R) and concomitant heparin should be stopped immediately; because INTEGRILIN(R) inhibits platelet aggregation, caution should be employed when it is used with other drugs that affect hemostatic, including thrombolytics, oral anticoagulants, NSAIDs, and dipyridamole; use with other GP IIb-IIIa inhibitors should be avoided; INTEGRILIN(R) is cleared in part by the kidney and its plasma concentrations are doubled in patients with renal disease (CrCl <50 mL/min); therefore, the infusion dose of INTEGRILIN(R) needs to be reduced to 1mcg/kg/min in these patients; INTEGRILIN(R) is contraindicated in patients who are dependent upon renal dialysis (please see dosing guidelines); caution should be exercised when administering INTEGRILIN(R) to patients with a platelet count <100,000/mm3.
Full prescribing information for INTEGRILIN(R) is available at http://www.integrilin.com.
About Schering-Plough
Schering-Plough Corporation is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough’s vision is to earn the trust of the physicians, patients and customers served by its more than 33,500 people around the world. The company’s Web site is www.scheringplough.com.
SCHERING-PLOUGH DISCLOSURE NOTICE:
The information in this press release contains certain “forward-looking” statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements related to potential of INTEGRILIN(R) and further actions under the clinical trials. Forward-looking statements relate to expectations or forecasts of future events. Schering-Plough does not assume the obligation to update any forward-looking statement. Many factors could cause actual results to differ materially from the forward-looking statements of Schering-Plough, including market forces, economic factors, product availability, patent and other intellectual property protection, current and future branded, generic or over-the-counter competition, the regulatory process, and any developments following regulatory approval, among other uncertainties. For further details about these and other factors that may impact the forward-looking statements, see the Schering-Plough’s Securities and Exchange Commission filings, including Part II, Item 1A, “Risk Factors” in the third quarter 2007 10-Q of Schering-Plough.
CONTACT: Media, Lee A. Davies, +1-917-679-6368, or Investors, Alex Kelly,
+1-908-298-7436, both of Schering-Plough Corporation
Web site: http://www.schering-plough.com/
http://www.integrilin.com/
Company News On-Call: http://www.prnewswire.com/comp/777050.html /
