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NCT Number: NCT04273607

Anticoagulation-free VV ECMO for Acute Respiratory Failure

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).

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Key information

Conditions

Extracorporeal Membrane Oxygenation Complication Cardiovascular Diseases Embolism and Thrombosis Hemorrhage Pathologic Processes Pathological Conditions, Signs and Symptoms Thrombosis Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location status: Recruiting

Location contact

Eddy Fan, MD-PhD

CONTACT

[email protected]

+ 1 416 340 3601

Manuel Tisminestky, MD

SUB_INVESTIGATOR

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Subcutaneous Heparin

Drug

The intervention group will receive prophylactic heparin instead of standard of care therapeutic intravenous heparin

Other names: Enoxaparin or unfractionated heparin

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

Other outcomes

  1. 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).

  2. 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

  3. 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)

  4. 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

Study contacts

Contact information is provided by the study sponsor or research team.

Damian Ratano, MD

CONTACT

[email protected]

+1 416-340-3601

Eddy Fan, MD, PhD

CONTACT

[email protected]

+1 416-340-3601

Sponsors and collaborators

Lead sponsor

Damian Ratano

Other

Collaborators

  • The Physicians' Services Incorporated Foundation

Registry information

Official study title

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

Acronym: A-FREE ECMO

Important dates

Study start
2022
Primary completion
2026
Study completion
2027
First posted
Feb 18, 2020
Registry last updated
Jan 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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