Un-fractionated Heparin Versus Bivalirudin During Percutaneous Coronary Interventions (PCI) (ISAR-REACT-3)

March 12, 2010 updated by: Deutsches Herzzentrum Muenchen

Prospective, Randomized, Double-Blind, Active-Controlled, Multicenter Trial of Bivalirudin and Un-fractionated Heparin in Patients Undergoing Percutaneous Coronary Interventions. ISAR-REACT-3

The purpose of this study is to determine whether bivalirudin given during PCI is associated with better outcomes compared to un-fractionated heparin.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Thrombin plays a major role in acute coronary artery occlusions during percutaneous coronary interventions. Unfractionated heparin has been traditionally used during invasive coronary procedures to reduce the risk of thrombotic occlusion. Bivalirudin, a direct antithrombin inhibitor, has several advantages over unfractionated heparin: it acts independently of antithrombin and inhibits both free and clot-bound thrombin; it is not neutralized by circulating inhibitors; exhibits consistent dose-response characteristics, and does not cause thrombocytopenia. Previous studies have shown that use of bivalirudin among patients undergoing percutaneous coronary interventions is associated with better outcomes (death, myocardial infarction, urgent repeat revascularization or in-hospital major bleeding) as compared with unfractionated heparin and adjunctive use of glycoprotein IIb/IIIa platelet receptor inhibitors. However, previous studies have included patients treated with plain balloon angioplasty or stenting after inadequate pre-treatment with thienopyridines (ticlopidine or clopidogrel). Recent guidelines recommend that all patients undergoing percutaneous coronary interventions must receive a loading dose of 300 -600 mg of clopidogrel. A 600 mg loading dose of clopidogrel eliminates the need for glycoprotein IIb/IIIa platelet receptor inhibitors in adjunct to heparin. According to existing evidence antithrombotic regimens based on either bivalirudin or pre-treatment with 600 mg of clopidogrel in addition to UFH intraprocedurally, are effective strategies to reduce ischemic and hemorrhagic complications in patients with coronary artery disease undergoing PCI. At present, it is not known whether bivalirudin is superior to UHF in patients who have been optimally pre-treated with a loading dose of clopidogrel.

Study Type

Interventional

Enrollment (Actual)

4570

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Bad Krozingen, Germany, 79189
        • Herz-Zentrum
      • Bad Segeberg, Germany, 23795
        • Segeberger Kliniken
      • Munich, Germany, 80636
        • Deutsches Herzzentrum Muenchen
      • Munich, Germany, 81675
        • First Medizinische Klinik, Klinikum rechts der Isar

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients older than 18 years of age to undergo PCI
  • Clopidogrel loading at least 2 hrs prior to PCI according to the PCI guidelines
  • Informed, written consent

Exclusion Criteria:

  • Recent ST-elevation myocardial infarction within the last 48 hours
  • Cardiogenic shock
  • ACS and positive biomarkers (Troponin T > 0.03 µg/L)
  • Malignancies or other comorbid conditions (for example severe liver, renal and pancreatic disease) 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 within the last 6 weeks
  • Presence of diseases which have a high probability of vascular lesions and subsequent bleeding such as active gastric ulcer or active ulcerous colitis
  • Recent trauma or major surgery in the last month
  • Ophthalmic surgery or brain surgery in the last month
  • Retinopathies or vitreous body bleeding in the last month
  • History of intracranial bleeding or structural abnormalities (for example aneurysm of cerebral arteries)
  • Suspected aortic dissection; pericarditis and subacute bacterial endocarditis
  • Patient's refusal to blood transfusion
  • Oral anticoagulation therapy with coumarin derivative within the last 7 days
  • Treatment with UFH within 6 hours or low-molecular weight heparin within 8 hours before randomization
  • Treatment with bivalirudin within 24 hours before randomization
  • Severe uncontrolled hypertension >180/110 mmHg unresponsive to therapy
  • Planned staged PCI procedure within 30 days from index procedure or prior PCI within the last 30 days
  • Relevant hematologic deviations:hemoglobin < 100 g/L; platelet count < 100 x 109 /L
  • Glomerular filtration rate (GFR) < 30 ml/min or serum creatinine > 30 mg/L or dependence on renal dialysis
  • Known allergy to the study medications: aspirin, clopidogrel, UFH, bivalirudin; stainless steel; true anaphylaxis after prior exposure to contrast media
  • Known heparin-induced thrombocytopenia (Typ II)
  • Previous enrollment in this trial
  • Pregnancy (present, suspected or planned) or positive pregnancy test
  • Spinal, peridural and epidural anesthesia
  • Patient's inability to fully cooperate with the study protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A
bivalirudin is to be administered as an 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.
Drug: Bivalirudin
bivalirudin to be administered as an 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 Names:
  • ReoPro
Active Comparator: B
UFH given as an intravenous bolus of 140 units/kg. Double blinding will be maintained by using a double-dummy technique consisting of identical UFH and bivalirudin syringes and bivalirudin or placebo infusion bags.
Drug: Un-fractionated heparin
UFH is given as an intravenous bolus of 140 units/kg followed by infusion of placebo 1.75 mg/kg per hour for the duration of the procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Composite rate of death, myocardial infarction (MI),urgent target vessel revascularization (TVR) within 30 days or in-hospital major bleeding
Time Frame: 30 days
30 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Composite rate of death, MI or urgent TVR within 30 days
Time Frame: 30 days
30 days
Composite rate of death, MI or TVR at 1 year
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Deutsches Herzzentrum Muenchen

Investigators

  • Study Director: Franz-Josef Neumann, MD, Herz-Zentrum Bad Krozingen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2005

Primary Completion (Actual)

February 1, 2008

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

December 5, 2005

First Submitted That Met QC Criteria

December 5, 2005

First Posted (Estimate)

December 6, 2005

Study Record Updates

Last Update Posted (Estimate)

March 15, 2010

Last Update Submitted That Met QC Criteria

March 12, 2010

Last Verified

August 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GE IDE No. A01005
  • KKF 1.1-05

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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