Anticoagulation-free VV ECMO for Acute Respiratory Failure (A-FREE ECMO)

August 19, 2022 updated by: Damian Ratano

Anticoagulation-free VV ECMO for Acute Respiratory Failure: A Pilot Safety and Feasibility Randomized Clinical Trial

Currently international experts recommend therapeutic anticoagulation for veno-venous extracorporeal membrane oxygenation (VV-ECMO). Reports and case series suggest that the absence of therapeutic anticoagulation is safe for VV-ECMO. No randomized control trials have assessed this. The aim of this pilot study is to assess safety and feasibility of an "anticoagulation-free strategy" for veno-venous ECMO (VV-ECMO) in Acute respiratory distress syndrome (ARDS).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Although anticoagulation targets and monitoring strategies vary around the world, the current practice is still to anticoagulate patients on ECMO, mostly with UFH. However, the use of heparin coated circuits has changed their thrombogenicity. Preliminary data suggest that a low-dose unfractionated heparin (UFH) strategy is non-inferior to a therapeutic dose UFH. Indeed, in daily practice, when a patient on ECMO has severe bleeding complications, UFH is often stopped until the hemorrhagic issue is under control, sometimes for days. This has led some to hypothesize that anticoagulation might not be necessary for VV-ECMO, and a few case series report little to no increase in adverse events as a result. There are currently no randomized controlled trials comparing anticoagulation to no anticoagulation for patients supported with ECMO. Anticoagulation is, for physiological reasons, less necessary during VV-ECMO than VA-ECMO and this is the reason why our pilot study will focus on VV-ECMO only. Whereas the whole ECMO device is identical for both configurations, the risk of systemic embolization (e.g., stroke) and its severe complications is much higher in VA-ECMO where blood is reinjected directly into the systemic arterial system. Moreover, in the presence of severely decreased left ventricular function requiring VA-ECMO, the risk of left ventricular thrombus is very high and requires anticoagulation. During VV-ECMO, the risk of systemic embolization is low because the whole circuit is on the right side of the heart and relatively preserved biventricular function is needed to perform VV-ECMO

The hypothesis is that VV-ECMO is safe and feasible without therapeutic anticoagulation for adults with ARDS.

The objectives of this study is to assess, through a pilot study, the safety and feasibility of an "anticoagulation free strategy" for veno-venous ECMO (VV-ECMO) in acute respiratory failure

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Eddy Fan, MD, PhD
  • Phone Number: +1 416-340-3601
  • Email: eddy.fan@uhn.ca

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2N2
        • Recruiting
        • Toronto General Hospital
        • Contact:
        • Sub-Investigator:
          • Manuel Tisminestky, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult patient with ARDS on VV-ECMO

Exclusion Criteria:

  • Contraindication to anticoagulation with UFH (known heparin-induced thrombocytopenia, active hemorrhage, any surgery precluding the use of anticoagulation),
  • Indication for therapeutic anticoagulation (pulmonary embolism or deep vein thrombosis, chronic anticoagulation therapy before ECMO insertion)
  • Low-flow (<2 liters/min) VV-ECMO (ECCO2R)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: No anticoagulation
Participants in this arm will not receive unfractionated heparin during the course of ECMO. They will receive standard venous thromboembolism prophylaxis with subcutaneous enoxaparin or unfractionated heparin
Drug: Subcutaneous Heparin
The intervention group will receive prophylactic heparin instead of standard of care therapeutic intravenous heparin
Other Names:
  • Enoxaparin or unfractionated heparin
No Intervention: Anticoagulation, ECMO standard of care
Participants in this arm will receive the standard of care anticoagulation with unfractionated heparin during the course of ECMO.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ECMO associated thrombotic complications
Time Frame: through ECMO completion, an average of 14 days

Composite outcome of:

  • ECMO membrane oxygenator function assessed by trans-membrane pressure drop (> 10mmHg/l/min) and a membrane PaO2/FiO2 ratio (< 200mmHg)

    • Need to change ECMO circuit due to clotting or dysfunction
    • Platelets drop >50% in 24 hours and <50 /mm3
    • Development of a clinically significant thromboembolic event
  • Clinical deep vein thrombosis, clinically suspected and confirmed by ultrasound
  • Acute ischemic stroke, clinically suspected and confirmed by head-CT
through ECMO completion, an average of 14 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hemorrhagic complications
Time Frame: through ECMO completion, an average of 14 days

Hemorrhagic complications assessed and adapted as per Bleeding Academic Research Consortium (BARC)

  • Type 0: No bleeding
  • Type 1: Bleeding requiring transfusion of packed red blood cells (PRBC) or reduction of UFH
  • Type 2: Bleeding requiring transfusion of PRBC and reduction of UFH
  • Type 3: Life-threatening bleeding requiring, transfusion of PRBC, surgical intervention or discontinuation of ECMO
  • Type 4: Any fatal bleeding
through ECMO completion, an average of 14 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Increase in d-dimer levels
Time Frame: through ECMO completion, an average of 14 days

D-dimers level (>5000ng/ml or >50% increase in 24 h)

  • Need for transfusion of blood and blood-derived products related or not to a bleeding event
  • Coagulation parameters during the ECMO period
  • Amount of clot and fibrin visualized in the pre- and post-membrane side of the oxygenator daily (visual assessment) and after ECMO removal (assessed by a photographic quantification method).
through ECMO completion, an average of 14 days
Transfusion of blood and blood-derived products related or not to a bleeding event
Time Frame: through ECMO completion, an average of 14 days
Amount of blood products transfused to patients in each groups during the course of ECMO
through ECMO completion, an average of 14 days
Coagulation parameters on ECMO
Time Frame: through ECMO completion, an average of 14 days
Evaluation of fibrinogen (g/l), activated partial thromboplastin time (aPTT, seconds), prothrombin time (PT, seconds), thromboelastogram (if available), activated clotting time (ACT, seconds; if available)
through ECMO completion, an average of 14 days
Amount of clot and fibrin visualized in the pre- and post-membrane side
Time Frame: through ECMO completion, an average of 14 days
Pragmatic quantification of clot visualized on both sides of the oxygenator by direct evaluation and by a photographic quantification method
through ECMO completion, an average of 14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Damian Ratano

Collaborators

PSI Foundation, Toronto, Ontario

Investigators

  • Principal Investigator: Eddy Fan, MD, PhD, University Health Network, Toronto
  • Principal Investigator: Damian Ratano, MD, University Health Network, Toronto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

September 1, 2022

Primary Completion (Anticipated)

December 31, 2023

Study Completion (Anticipated)

June 30, 2024

Study Registration Dates

First Submitted

February 11, 2020

First Submitted That Met QC Criteria

February 13, 2020

First Posted (Actual)

February 18, 2020

Study Record Updates

Last Update Posted (Actual)

August 24, 2022

Last Update Submitted That Met QC Criteria

August 19, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19-5692.0

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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