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

This study has been completed.
Sponsor:
Information provided by:
Deutsches Herzzentrum Muenchen
ClinicalTrials.gov Identifier:
NCT00262054
First received: December 5, 2005
Last updated: March 12, 2010
Last verified: August 2008
  Purpose

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


Condition Intervention Phase
Coronary Disease
Angina Pectoris
Drug: Bivalirudin
Drug: Un-fractionated 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: Prospective, Randomized, Double-Blind, Active-Controlled, Multicenter Trial of Bivalirudin and Un-fractionated Heparin in Patients Undergoing Percutaneous Coronary Interventions. ISAR-REACT-3

Resource links provided by NLM:


Further study details as provided by Deutsches Herzzentrum Muenchen:

Primary Outcome Measures:
  • Composite rate of death, myocardial infarction (MI),urgent target vessel revascularization (TVR) within 30 days or in-hospital major bleeding [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Composite rate of death, MI or urgent TVR within 30 days [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Composite rate of death, MI or TVR at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 4570
Study Start Date: November 2005
Study Completion Date: May 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00262054

Locations
Germany
Herz-Zentrum
Bad Krozingen, Germany, 79189
Segeberger Kliniken
Bad Segeberg, Germany, 23795
Deutsches Herzzentrum Muenchen
Munich, Germany, 80636
First Medizinische Klinik, Klinikum rechts der Isar
Munich, Germany, 81675
Sponsors and Collaborators
Deutsches Herzzentrum Muenchen
Investigators
Study Chair: Albert Schomig, MD Deutsches Herzzentrum Muenchen
Principal Investigator: Adnan Kastrati, MD Deutsches Herzzentrum Muenchen
Study Director: Franz-Josef Neumann, MD Herz-Zentrum Bad Krozingen
  More Information

Publications:

Responsible Party: Prof. A. Schömig, Deutsches Herzzentrum Munich
ClinicalTrials.gov Identifier: NCT00262054     History of Changes
Other Study ID Numbers: GE IDE No. A01005, KKF 1.1-05
Study First Received: December 5, 2005
Last Updated: March 12, 2010
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Deutsches Herzzentrum Muenchen:
coronary disease

Additional relevant MeSH terms:
Angina Pectoris
Coronary Disease
Coronary Artery Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Arteriosclerosis
Arterial Occlusive Diseases
Calcium heparin
Bivalirudin
Heparin
Hirudins
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 22, 2014