ENDOvascular Interventions With AngioMAX: The ENDOMAX Trial

NCT01913483 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: MDCO-BIV-12-03
• Study Type: interventional
• Target: 732
• Locations: 1 country
• Sites: 39

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.

Conditions

Peripheral Endovascular Interventions; Bleeding

Outcome Measures

Primary Outcomes (1)

• 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)

  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.

  Study drug administration (Day 1) up to 48 h post study drug initiation or at hospital discharge, whichever occurs first

Secondary Outcomes (2)

• 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 Administration

  Study drug administration (Day 1) up to 48 h post study drug initiation or at hospital discharge, whichever occurs first

• Participants With MI, Stroke/TIA, URV, Death, or Minor Bleeding Up to Day 30

  Study drug initiation (Day 1) up to 30 days

Study Arms (2)

Bivalirudin

EXPERIMENTAL

Bivalirudin 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 \[mL/min\]).

Drug: Bivalirudin

Unfractionated Heparin

ACTIVE COMPARATOR

UFH 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.

Drug: Unfractionated Heparin

Interventions

Bivalirudin DRUG

Bivalirudin is an anticoagulant that binds directly to thrombin in a bivalent and reversible fashion.

Also known as: AngioMAX, Angiox

Bivalirudin

Unfractionated Heparin DRUG

Unfractionated heparin is an anticoagulant.

Also known as: Heparin

Unfractionated Heparin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Medicines Company: lead

Study Sites (39)

Tri-Lakes Research

Hot Springs, Arkansas, 71901, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305-5407, United States

Location

Clearwater Cardiovascular and Interventional Consultants

Clearwater, Florida, 33756, United States

Location

Florida Research Network

Gainesville, Florida, 32605, United States

Location

The Cardiac and Vascular Institute

Gainesville, Florida, 32605, United States

Location

Baptist Cardiac & Vascular Institute

Miami, Florida, 33176, United States

Location

Florida Hospital

Orlando, Florida, 32803, United States

Location

Peoria Radiology Research & Education Foundation

Peoria, Illinois, 61637, United States

Location

Midwest Cardiovascular Research Foundation

Davenport, Iowa, 52803, United States

Location

Kentucky Heart Foundation - King's Daughters Medical Center

Ashland, Kentucky, 41101, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

VA Boston Healthcare System

Boston, Massachusetts, 02132, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Cape Cod Research Institute

Hyannis, Massachusetts, 02601, United States

Location

Michigan Heart

Ypsilanti, Michigan, 48197, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Deborah Heart and Lung Center

Browns Mills, New Jersey, 08015, United States

Location

Holy Name Medical Center

Teaneck, New Jersey, 07666, United States

Location

New Mexico Heart Institute

Albuquerque, New Mexico, 87102, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Stony Brook Medicine

Stony Brook, New York, 11794, United States

Location

Novant Health Heart and Vascular Institute

Charlotte, North Carolina, 28204, United States

Location

LeBauer Cardiovascular Research Foundation

Greensboro, North Carolina, 27401, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Jobst Vascular Institute

Toledo, Ohio, 43606, United States

Location

Integris - Baptist Medical Center

Oklahoma City, Oklahoma, 73112, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

AnMed Health

Anderson, South Carolina, 29621, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Texas Tech University Health Science Center

Lubbock, Texas, 79430, United States

Location

Scott and White Hospital

Temple, Texas, 76508, United States

Location

Alpine Research

Ogden, Utah, 84403, United States

Location

INOVA Alexandria Hospital

Alexandria, Virginia, 22304, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Hemorrhage

Interventions

bivalirudin; Heparin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Chief Medical Executive
• Organization: Miami Cardiac & Vascular Institute, Baptist Health South Florida

MCVI@BaptistHealth.net

800-273-2700

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2013
• First Posted: August 1, 2013
• Study Start: September 24, 2013
• Primary Completion: March 16, 2016
• Study Completion: March 16, 2016
• Last Updated: May 30, 2017
• Results First Posted: May 30, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (39)