Randomized Comparison of Abciximab Plus Heparin With Bivalirudin in Acute Coronary Syndrome (ISAR-REACT-4)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Deutsches Herzzentrum Muenchen
ClinicalTrials.gov Identifier:
NCT00373451
First received: September 7, 2006
Last updated: May 7, 2012
Last verified: May 2012

September 7, 2006
May 7, 2012
July 2006
May 2011   (final data collection date for primary outcome measure)
Composite of death, large recurrent myocardial infarction (MI), urgent target vessel revascularization (TVR) or major bleeding [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
Composite end point of death, large recurrent MI, urgent TVR or major bleeding within 30 days from randomization
Complete list of historical versions of study NCT00373451 on ClinicalTrials.gov Archive Site
  • Composite end point of death, any recurrent myocardial infarction or urgent TVR [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Major bleedings [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
30-day composite rate of death, any recurrent MI or urgent TVR or 30-day major bleeding rate
Not Provided
Not Provided
 
Randomized Comparison of Abciximab Plus Heparin With Bivalirudin in Acute Coronary Syndrome
Randomized, Double-Blind, Active-Controlled, Multicenter Trial of Abciximab And Bivalirudin in Patients With Non-ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Interventions (ISAR-REACT-4)

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Myocardial Infarction
  • Coronary Disease
  • Drug: 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)
    Other Name: ReoPro
  • 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)
    Other Name: Angiox
  • Drug: Heparin
    i.v. bolus of 70 units/kg/body weight of unfractionated heparin
    Other Name: unfractionated heparin
  • Experimental: Abciximab+UFH
    Abciximab and unfractionated heparin as bolus given during PCI and abciximab-perfusion for 12 hours after PCI
    Interventions:
    • Drug: Abciximab + UFH
    • Drug: Heparin
  • Active Comparator: Bivalirudin
    Bivalirudin given only during PCI
    Intervention: Drug: Bivalirudin

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1721
July 2011
May 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
Germany,   Italy
 
NCT00373451
GE IDE No. A01106
Yes
Deutsches Herzzentrum Muenchen
Deutsches Herzzentrum Muenchen
Not Provided
Study Chair: Albert Schoemig, MD Deutsches Herzzentrum Muenchen
Principal Investigator: Adnan Kastrati, MD Deutsches Herzzentrum Muenchen
Deutsches Herzzentrum Muenchen
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP