Fixed Low-dose Heparin Versus Standard Adjusted-dose Heparin Infusion in Adults Receiving Venovenous ECMO With a Heparin Bonded Circuit.

Fixed Low-dose Heparin Versus Standard Adjusted-dose Heparin Infusion in Adults Receiving Venovenous Extracorporeal Membrane Oxygenation (ECMO) With a Heparin Bonded Circuit.

Heparin is a blood thinner used to prevent blood clots in patients on a form of life-support called ECMO. Heparin can cause bleeding - the most common complication of ECMO. New materials used in ECMO machines may help prevent clots - this could allow the use of lower doses of heparin which might reduce the risk of bleeding. Our study will compare low dose to high dose heparin in patients on ECMO. We think low dose heparin may be adequate to prevent clotting, but may cause less bleeding and be safer for patients.

Study Overview

• Status: Withdrawn
• Conditions: Bleeding; Acute Respiratory Failure; Extracorporeal Membrane Oxygenation Complication
• Intervention / Treatment: Drug: HEP-IV

Detailed Description

Intravenous heparin is considered standard therapy to prevent clotting complications in patients on ECMO, however the optimal method of heparin dosing has not yet been determined. International surveys have shown that most ECMO centers use adjusted dose heparin to achieve an activated clotting time of at least 180 seconds. However, heparin may contribute to the most common complication of ECMO - bleeding. Advances in material technology have potentially reduced the thrombogenicity of modern ECMO circuits. Our observational data suggest that fixed low dose heparin infusion may reduce the rate of bleeding complications from 75% to 50% compared to standard adjusted-dose heparin, without increasing clotting complications. We intend to perform a randomized controlled trial in adults receiving venovenous ECMO comparing these two heparin regimens. The main outcome measures are bleeding complications and oxygenator failure due to clotting. A safety committee will monitor the results of the study. Power calculations indicate a sample size of 110 patients is required, which we estimate will take us five years to achieve.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner - University Medical Center Phoenix

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:

• on ECMO for acute respiratory failure, achieving ECMO blood flow rate >3L/min,
• patient or surrogate able to speak/understand English or Spanish

Exclusion Criteria:

• History of heparin-induced thrombocytopenia, decision by clinicians to run ECMO off heparin due to high bleeding risk,
• pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Adjusted-dose heparin; Patients in this arm of the study will receive intravenous unfractionated heparin at a dose adjusted to achieve an activated clotting time of 180-200 seconds.	Drug: HEP-IV; Other Names: heparin
Other: Fixed low-dose heparin; Patients in this arm of the study will receive intravenous unfractionated heparin at 500 units/hour without activated clotting time monitoring.	Drug: HEP-IV; Other Names: heparin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
significant bleeding complications	requires surgery, >1 unit packed blood cell transfusion or is intracranial, pulmonary or retroperitoneal	intraoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxygenator failure	Requirement to replace oxygenator due to clotting	intraoperative
cerebral vascular event (stroke)		intraoperative

Collaborators and Investigators

• Sponsor: University of Arizona
• Investigators: Principal Investigator: Robert Raschke, MD, Banner University Medical Center

Publications and helpful links

General Publications

• Esper SA, Levy JH, Waters JH, Welsby IJ. Extracorporeal membrane oxygenation in the adult: a review of anticoagulation monitoring and transfusion. Anesth Analg. 2014 Apr;118(4):731-43. doi: 10.1213/ANE.0000000000000115.
• Poulos EM, Raschke R, Amabile O et al. A Nonrandomized comparison of three different heparin infusion strategies for patients receiving venovenous extracorporeal membrane oxygenation. Am J Respir Crit Care Med 2014;189: A4499.

Helpful Links

• ELSO anticoagulation guideline

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): February 1, 2021

Study Registration Dates

• First Submitted: November 15, 2016
• First Submitted That Met QC Criteria: November 16, 2016
• First Posted (Estimate): November 17, 2016

Study Record Updates

• Last Update Posted (Actual): August 21, 2017
• Last Update Submitted That Met QC Criteria: August 16, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: extracorporeal membrane oxygenation; intravenous heparin
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin
• Other Study ID Numbers: 1609884386

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO