Bivalirudin vs Heparin in ECMO Patients

A Randomized Study Comparing Bivalirudin vs Heparin in Patients With Extracorporeal Membrane Oxygenator (ECMO) Support

This is an open label, randomized study comparing the clinical outcomes of unfractionated Heparin and Bivalirudin for anticoagulation in adult subjects requiring ECMO support.

Study Overview

• Status: Withdrawn
• Conditions: Extracorporeal Membrane Oxygenation Complication
• Intervention / Treatment: Drug: Bivalirudin Injection [Angiomax]; Drug: Heparin Sodium

Detailed Description

This open label randomized study will compare the clinical outcomes of patients on ECMO who are anticoagulated with Heparin and Bivalirudin. Patients will be anticoagulated with a heparin bolus at the commencement of ECMO per standard of care, as there will be insufficient time to randomize these frequently emergent patients. Consent for the study will be obtained from a legally authorized representative Prior to starting a continuous infusion of maintenance anticoagulation, patients will be randomized to bivalirudin or heparin. Outcome measures are bleeding, thrombosis, development of Heparin Induced thrombocytopenia, number of cross-overs between the two research arms, circuit failures, decannulation, deaths and discharges from hospital.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University

Participation Criteria

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:

• Adult patients on veno-arterial (VA) or veno-venous (VV)ECMO

Exclusion Criteria:

• Patient or surrogate decision makers cannot provide informed consent.
• Patients who have intolerance to either heparin or bivalirudin
• Patients who received any form of thrombolytic therapy within the past 30 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bivalirudin Injection (Angiomax); This arm will receive intravenous Bivalirudin for ECMO anticoagulation for the extent of ECMO support or 7 days whichever comes first	Drug: Bivalirudin Injection [Angiomax]; Intravenous Bivalirudin titrated to Activated Clotting Time (ACT) levels
Active Comparator: Heparin Sodium; This arm will receive intravenous Heparin Sodium for ECMO anticoagulation for the extent of ECMO support or 7 days whichever comes first	Drug: Heparin Sodium; Intravenous Heparin titrated to Partial ThromboplastinTime (PTT) levels

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of heparin-induced thrombocytopenia (HIT) events	This will be assessed by serum platelet factor 4 antibody level	30 days
Number of Cross-overs between arms	This will be assessed by number of cross over of patients from one arm to the other anti-coagulation arm for any particular clinical reason. Crossover patients will remain in the study and we will continue to collect protocol driven data. These patients will be analyzed separately from those with no cross-over.	30 days
Number of circuit failures requiring a circuit exchange	Will be determined by total number of circuit exchanges needed in ECMO circuit due to thrombosis. Circuit exchanges may be done due to lack of adequate gas exchange or increased resistance pre and post oxygenator >50mmHg, circuit thrombosis or failure requiring emergent decannulation	30 days
Thrombotic events	Collect number of thrombotic events, defined as any of the following events; embolic strokes, embolic end-organ ischemia, embolic ischemia to limbs, deep vein thrombosis or venous thromboembolism, Oxygenator effectiveness measured by resistance, Alveolar-arterial oxygen gradient and carbon dioxide elimination	30 days
Bleeding events	Will be assessed by the total number of one or more of the following: Chest tube output of blood, number of take-backs to operating room for bleeding, number of Hemorrhagic strokes, Gastrointestinal bleeding, Retroperitoneal hemorrhage, number of cessations of anticoagulation for refractory bleeding and any use of antifibrinolytics or factor VII	30 days
Renal failure	Defined as initiation of renal replacement therapy for kidney injury that develops on ECMO or increase in serum creatinine by more than 2 times its baseline or decrease in Glomerular Filtration Rate by more than 50% or urine output less than 0.3 mL/kg/hr. We will determine the number of patients with renal failure	30 days
Number of Transfusions	This will be assessed by any of the following: number of utilizations of packed red blood cells and utilization of fresh frozen plasma, utilization of platelets, utilization of cryoprecipitate, utilization of anti-thrombin III, utilization of factor VII, utilization of prothrombin complex concentrate	30 days
Number of emergent decannulations	This will be assessed by the number of times patient is separated from ECMO	30 days
Number of patients surviving to discharge	This will be assessed by the number of patients in each arm who survive to discharge	30 days

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Glenn Whitman, M.D., Johns Hopkins University

Publications and helpful links

General Publications

• Hasegawa D, Sato R, Prasitlumkum N, Nishida K, Keaton B, Acquah SO, Im Lee Y. Comparison of Bivalirudin Versus Heparin for Anticoagulation During Extracorporeal Membrane Oxygenation. ASAIO J. 2022 Oct 4. doi: 10.1097/MAT.0000000000001814. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2021
• Primary Completion (Anticipated): June 1, 2021
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: October 11, 2018
• First Submitted That Met QC Criteria: October 11, 2018
• First Posted (Actual): October 16, 2018

Study Record Updates

• Last Update Posted (Actual): January 19, 2021
• Last Update Submitted That Met QC Criteria: January 14, 2021
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Heparin; Bivalirudin; Calcium heparin
• Other Study ID Numbers: IRB00176475

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No