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
  Purpose

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.


Condition Intervention Phase
Myocardial Infarction
Coronary Disease
Drug: Abciximab + UFH
Drug: Bivalirudin
Drug: Heparin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Deutsches Herzzentrum Muenchen:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 1721
Study Start Date: July 2006
Study Completion Date: July 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Abciximab+UFH
Abciximab and unfractionated heparin as bolus given during PCI and abciximab-perfusion for 12 hours after PCI
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: Heparin
i.v. bolus of 70 units/kg/body weight of unfractionated heparin
Other Name: unfractionated heparin
Active Comparator: Bivalirudin
Bivalirudin given only during PCI
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00373451

Locations
Germany
Herz-Zentrum Bad Krozingen
Bad Krozingen, Germany, 79189
Herz- und Gefaessklinik, Kardiologie
Bad Neustadt, Germany, 97616
Vivantes Klinikum Neukoelln
Berlin, Germany, 12351
Vivantes Klinikum im Friedrichshain
Berlin, Germany, 10249
Vivantes Auguste Viktoria Klinikum
Berlin, Germany, 12157
Medizinische Klinik, Klinikum rechts der Isar
Muenchen, Germany, 81675
Deutsches Herzzentrum Muenchen
Munich, Germany, 80636
Marienhospital Osnabrueck
Osnabrueck, Germany, 49074
Italy
Ospedale Cageggi
Firenze, Italy, 50134
Sponsors and Collaborators
Deutsches Herzzentrum Muenchen
Investigators
Study Chair: Albert Schoemig, MD Deutsches Herzzentrum Muenchen
Principal Investigator: Adnan Kastrati, MD Deutsches Herzzentrum Muenchen
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Deutsches Herzzentrum Muenchen
ClinicalTrials.gov Identifier: NCT00373451     History of Changes
Other Study ID Numbers: GE IDE No. A01106
Study First Received: September 7, 2006
Last Updated: May 7, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Deutsches Herzzentrum Muenchen:
NSTEMI

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Acute Coronary Syndrome
Coronary Disease
Coronary Artery Disease
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms
Arteriosclerosis
Arterial Occlusive Diseases
Calcium heparin
Abciximab
Bivalirudin
Heparin
Hirudins
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014