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ENDOvascular Interventions With AngioMAX: The ENDOMAX Trial

Phase 3
Terminated
Conditions
Peripheral Endovascular Interventions
Bleeding
Interventions
Registration Number
NCT01913483
Lead Sponsor
The Medicines Company
Brief Summary

The primary objective of the study is to test whether anticoagulation with bivalirudin results in fewer major bleeding complications compared with unfractionated heparin (UFH) in participants undergoing peripheral endovascular interventions (PEI). The secondary objective is to test whether there were potential benefits from bivalirudin therapy on other clinically important events such as death, myocardial infarction (MI), stroke and/or transient ischemic attack (TIA), amputation, unplanned repeat revascularization (URV), and minor bleeding, as well as potential economic benefits that may result from improved clinical outcomes.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
732
Inclusion Criteria
  • Participants ≥ 18 years of age

  • Must be undergoing one of the following PEI procedures:

    • Carotid artery stenting
    • Lower Extremity Interventions (LEI) for Critical Limb Ischemia
    • LEI for claudication
  • Provide written informed consent prior to any study-specific procedure being performed

Exclusion Criteria
  • Any known contra-indication to the use of bivalirudin or UFH
  • Acute limb ischemia
  • Planned amputation regardless of the outcome of the PEI
  • Dialysis dependent
  • Weight less than 38 kg or more than 202 kg
  • History of any bleeding diathesis or severe hematological disease
  • History of intra-cranial: mass, aneurysm, arteriovenous malformation or hemorrhage
  • Gastrointestinal or genitourinary bleeding within the 30 days prior to randomization
  • Any surgery (excluding punch or shave skin biopsy) within the 30 days prior to randomization
  • Concomitant percutaneous coronary intervention
  • Any percutaneous coronary, endovascular, or structural heart disease procedure within 30 days prior to randomization
  • International normalized ratio >1.7 within 24 h prior to the index procedure
  • Administration of therapeutic doses of UFH within 30 min prior to the index procedure (a low dose [≤2000 U] of heparin is permitted during the diagnostic angiogram prior to the intervention)
  • Administration of enoxaparin within 8 h; other low molecular weight heparins or fondaparinux within 24 h; any oral anti-Xa or antithrombin agent within 48 h; or thrombolytics, glycoprotein inhibitors, or warfarin within 72 h prior to the index procedure
  • Severe contrast allergy that cannot be pre-medicated
  • Procedures performed by radial access when they are intended as the primary access site for the index procedure
  • Known or suspected pregnant women or nursing mothers
  • Previous enrollment in this study (MDCO-BIV-12-03)
  • Participation in other investigational drug or device trials within 30 days prior to randomization
  • Participants who, for any reason, are deemed by the investigator to be inappropriate for this study

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
BivalirudinBivalirudinBivalirudin was administered as an intravenous (IV) bolus and infusion for the duration of the procedure (mean duration of 48.6 minutes). The bolus (0.75 milligrams (mg)/kilogram \[kg\]) was administered via systemic IV administration. Immediately after the bolus, an IV infusion of bivalirudin was initiated at a dose of 1.75 mg/kg/hour (h) (or 1 mg/kg/h for participants with an estimated glomerular filtration rate \[eGFR\] \<30 milliliters/minute \[mL/min\]).
Unfractionated HeparinUnfractionated HeparinUFH was administered as an IV bolus for the duration of the procedure (mean duration of 48.6 minutes). UFH was administered via weight-based IV bolus at a dose of 50 units (U)/kg to 70 U/kg. Additional bolus doses were administered per standard-of-care use.
Primary Outcome Measures
NameTimeMethod
Participants With Bleeding Academic Research Consortium Type 3 or Greater (BARC ≥3) Events Up to 48 h or at Hospital Discharge, As Adjudicated by the Independent Clinical Events Committee (CEC)Study drug administration (Day 1) up to 48 h post study drug initiation or at hospital discharge, whichever occurs first

BARC ≥3 includes:

Type 3a-3c: clinical, laboratory, and/or imaging evidence of bleeding, which includes any transfusion with overt bleeding, bleeds that result in surgical intervention or administration of IV vasoactive drugs, overt bleeds with a hemoglobin drop greater than or equal to 3 grams (g)/deciliters (dL) to greater than or equal to 5 g/dL, cardiac tamponade caused by bleeding, intracranial hemorrhage, and intraocular bleeds that compromise vision.

Type 4: (Coronary Artery Bypass Grafting-related Bleeding) includes perioperative intracranial bleeding within 48 h, bleeds that result in reoperation following closure of sternotomy for the purpose of controlling bleeding, bleeds that result in treatment with transfusion of ≥5 U of whole blood or packed red blood cells within a 48-h period; and chest tube output ≥2 liters within a 24-h period.

Type 5: fatal bleeding that directly results in death that is either clinically suspicious or is confirmed as the cause of death.

Secondary Outcome Measures
NameTimeMethod
Participants With Myocardial Infarction (MI), Stroke/Transient Ischemic Attack (TIA), Unplanned Repeat Revascularization (URV), Death, and Minor Bleeding Up to 48 h Post Study Drug AdministrationStudy drug administration (Day 1) up to 48 h post study drug initiation or at hospital discharge, whichever occurs first

Outcome assessments at 48 h post study drug initiation include bleeding events defined as BARC Type 2 or greater (BARC ≥2), bleeding events defined as thrombolysis in myocardial infarction (TIMI) major and TIMI minor, and net adverse clinical events (NACE) as adjudicated by the CEC (NACE=death, MI, stroke/TIA, amputations, URV, or bleeding events defined as BARC ≥3).

In addition to Type 3(a-c), 4, and 5, BARC ≥2 also includes Type 2 bleeding, which is any overt, actionable sign of hemorrhage (more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for Type 3, 4, or 5, but does meet at least one of the following criteria of: requiring nonsurgical, medical intervention by a health-care professional; leading to hospitalization or increased level of care; prompting evaluation.

Participants With MI, Stroke/TIA, URV, Death, or Minor Bleeding Up to Day 30Study drug initiation (Day 1) up to 30 days

Outcome assessments at Day 30 include NACE, Major Adverse Clinical Events (MACE=death, MI, stroke/TIA, amputation, or URV), and bleeding defined as BARC ≥2, as adjudicated by the CEC.

In addition to Type 3(a-c), 4, and 5, BARC ≥2 also includes Type 2 bleeding, which is any overt, actionable sign of hemorrhage (more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for Type 3, 4, or 5, but does meet at least one of the following criteria of: requiring nonsurgical, medical intervention by a health-care professional; leading to hospitalization or increased level of care; prompting evaluation.

Trial Locations

Locations (39)

Clearwater Cardiovascular and Interventional Consultants

🇺🇸

Clearwater, Florida, United States

Deborah Heart and Lung Center

🇺🇸

Browns Mills, New Jersey, United States

Stony Brook Medicine

🇺🇸

Stony Brook, New York, United States

Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

Icahn School of Medicine at Mount Sinai

🇺🇸

New York, New York, United States

University of Cincinnati

🇺🇸

Cincinnati, Ohio, United States

Peoria Radiology Research & Education Foundation

🇺🇸

Peoria, Illinois, United States

Michigan Heart

🇺🇸

Ypsilanti, Michigan, United States

Weill Cornell Medical College

🇺🇸

New York, New York, United States

Baptist Cardiac & Vascular Institute

🇺🇸

Miami, Florida, United States

Tri-Lakes Research

🇺🇸

Hot Springs, Arkansas, United States

Cleveland Clinic Foundation

🇺🇸

Cleveland, Ohio, United States

Beth Israel Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

Florida Research Network

🇺🇸

Gainesville, Florida, United States

Cape Cod Research Institute

🇺🇸

Hyannis, Massachusetts, United States

Stanford Hospital and Clinics

🇺🇸

Stanford, California, United States

Swedish Medical Center

🇺🇸

Seattle, Washington, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Integris - Baptist Medical Center

🇺🇸

Oklahoma City, Oklahoma, United States

Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

Alpine Research

🇺🇸

Ogden, Utah, United States

Florida Hospital

🇺🇸

Orlando, Florida, United States

The Cardiac and Vascular Institute

🇺🇸

Gainesville, Florida, United States

Midwest Cardiovascular Research Foundation

🇺🇸

Davenport, Iowa, United States

Kentucky Heart Foundation - King's Daughters Medical Center

🇺🇸

Ashland, Kentucky, United States

VA Boston Healthcare System

🇺🇸

Boston, Massachusetts, United States

New Mexico Heart Institute

🇺🇸

Albuquerque, New Mexico, United States

Columbia University Medical Center

🇺🇸

New York, New York, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

INOVA Alexandria Hospital

🇺🇸

Alexandria, Virginia, United States

LeBauer Cardiovascular Research Foundation

🇺🇸

Greensboro, North Carolina, United States

Holy Name Medical Center

🇺🇸

Teaneck, New Jersey, United States

Novant Health Heart and Vascular Institute

🇺🇸

Charlotte, North Carolina, United States

Scott and White Hospital

🇺🇸

Temple, Texas, United States

AnMed Health

🇺🇸

Anderson, South Carolina, United States

Jobst Vascular Institute

🇺🇸

Toledo, Ohio, United States

Texas Tech University Health Science Center

🇺🇸

Lubbock, Texas, United States

University of Virginia Health System

🇺🇸

Charlottesville, Virginia, United States

Rhode Island Hospital

🇺🇸

Providence, Rhode Island, United States

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