Randomized Comparison of Abciximab Plus Heparin With Bivalirudin in Acute Coronary Syndrome

NCT ID: NCT00373451

Last Updated: 2012-05-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 1721 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-07-31
• Study Completion Date: 2011-07-31

Brief Summary

The purpose of this study is to determine which of these anti-clotting medications, abciximab plus unfractionated heparin or bivalirudin, is more effective to prevent thrombotic and bleeding complications in patients suffering from a heart attack and undergoing coronary intervention.

Detailed Description

Non-ST elevation myocardial infarction (NSTEMI) is associated with an increased risk of death and is a major reason for hospital admissions. Most frequently, the sequence of events that leads to NSTEMI is characterized by a disrupted atherosclerotic plaque, platelet activation and aggregation, thrombus formation and microembolizations. Patients with NSTEMI are treated with an early invasive strategy and there is intensive work in progress to define the optimal antithrombotic therapy to be used in adjunct to percutaneous coronary intervention (PCI) in these patients. Bivalirudin, a direct thrombin inhibitor, and the glycoprotein IIb/IIIa inhibitor (GPI) abciximab have been in the focus of recent trials in patients with acute coronary syndrome (ACS). In a recent randomized, open-label trial (ACUITY trial), patients with the suspicion of ACS on the basis of the type of anginal symptoms, ST-segment displacement, elevated biomarkers or several risk indicators were randomized to receive bivalirudin alone with bail-out GPIs, bivalirudin plus GPIs, or heparin/low-molecular weight heparin plus a GPI. The GPIs most frequently used were eptifibatide and tirofiban. Abciximab was given in only < 9% of the cases. In another randomized, double-blind, placebo-controlled trial (ISAR-REACT-2) including ACS patients undergoing PCI, abciximab was administered in cath lab and was associated with a significant reduction of ischemic events in patients with NSTEMI, and did not lead to a measurable increase in major bleeding complications. However, it is not known whether abciximab is also superior to bivalirudin in patients with NSTEMI. We designed this study to assess whether abciximab added to unfractionated heparin is superior to bivalirudin in patients with NSTEMI.

Conditions

Myocardial Infarction; Coronary Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Abciximab+UFH

Abciximab and unfractionated heparin as bolus given during PCI and abciximab-perfusion for 12 hours after PCI

Group Type: EXPERIMENTAL

Abciximab + UFH

Intervention Type: DRUG

Abciximab (0.25 mg/kg of body weight bolus, followed by a 0.125 µg/kg/minute \[maximum of 10 µg/minute\] infusion for 12 hours)

Heparin

Intervention Type: DRUG

i.v. bolus of 70 units/kg/body weight of unfractionated heparin

Bivalirudin

Bivalirudin given only during PCI

Group Type: ACTIVE_COMPARATOR

Bivalirudin

Intervention Type: DRUG

Bivalirudin (intravenous bolus of 0.75 mg/kg prior to the start of the intervention, followed by infusion of 1.75 mg/kg per hour for the duration of the procedure)

Interventions

Abciximab + UFH

Abciximab (0.25 mg/kg of body weight bolus, followed by a 0.125 µg/kg/minute \[maximum of 10 µg/minute\] infusion for 12 hours)

Intervention Type: DRUG

Bivalirudin

Bivalirudin (intravenous bolus of 0.75 mg/kg prior to the start of the intervention, followed by infusion of 1.75 mg/kg per hour for the duration of the procedure)

Intervention Type: DRUG

Heparin

i.v. bolus of 70 units/kg/body weight of unfractionated heparin

Intervention Type: DRUG

Other Intervention Names

ReoPro; Angiox; unfractionated heparin

Eligibility Criteria

Inclusion Criteria

• Episode of unstable angina
• Elevated cardiac markers
• Angiographic lesions requiring PCI
• Informed, written consent

Exclusion Criteria

• Age < 18 years and > 80 years
• ST-segment elevation acute myocardial infarction within 48 hours
• Cardiogenic shock
• Pericarditis
• Malignancies or other comorbid conditions with life expectancy less than one year or that may result in protocol non-compliance
• Active bleeding; bleeding diathesis; history of gastrointestinal or genitourinary bleeding, recent trauma or major surgery in the last month; history of intracranial bleeding or structural abnormalities; suspected aortic dissection; pericarditis; and patient's refusal to blood transfusion
• Oral anticoagulation therapy with coumarin derivative within the last 7 days
• Recent use of GPIIb/IIIa inhibitors within 14 days
• Treatment with unfractionated heparin within 4 hours unless ACT > 150sec; or low-molecular weight heparin within 8 hours before randomization
• Treatment with bivalirudin within 24 hours before randomization
• Severe uncontrolled hypertension > 180/110 mm Hg unresponsive to therapy
• Planned staged PCI procedure within 30 days from index procedure or prior PCI within the last 30 days
• Relevant hematologic deviations
• Glomerular filtration rate (GFR) < 30 ml/min or serum creatinine > 30 mg/L or dependence on renal dialysis
• Known allergy or intolerance to the study medications, stainless steel or true anaphylaxis after prior exposure to contrast media
• Previous enrollment in this trial
• Women who are known to be pregnant, who are of childbearing potential and test positive for pregnancy, who have given birth within the last 90 days, who are breastfeeding
• Patient's inability to fully cooperate with the study protocol

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Deutsches Herzzentrum Muenchen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Albert Schoemig, MD

Role: STUDY_CHAIR

Deutsches Herzzentrum Muenchen

Adnan Kastrati, MD

Role: PRINCIPAL_INVESTIGATOR

Deutsches Herzzentrum Muenchen

Locations

Herz-Zentrum Bad Krozingen

Bad Krozingen, , Germany

Herz- und Gefaessklinik, Kardiologie

Bad Neustadt an der Saale, , Germany

Vivantes Klinikum im Friedrichshain

Berlin, , Germany

Vivantes Auguste Viktoria Klinikum

Berlin, , Germany

Vivantes Klinikum Neukoelln

Berlin, , Germany

Deutsches Herzzentrum Muenchen

Munich, , Germany

Medizinische Klinik, Klinikum rechts der Isar

München, , Germany

Marienhospital Osnabrueck

Osnabrück, , Germany

Ospedale Cageggi

Florence, , Italy

Countries

Germany; Italy

References

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Other Identifiers

GE IDE No. A01106

Identifier Type: -

Identifier Source: org_study_id