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Extracorporeal Membrane Oxygenation ComplicationPhase 2/3A-FREE ECMONCT04273607

Anticoagulation-free VV ECMO for Acute Respiratory Failure

A Phase 2/3 study testing Subcutaneous Heparin in people with Extracorporeal Membrane Oxygenation Complication, run by Damian Ratano at 1 site in Canada.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Subcutaneous Heparin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteCanada
Study dates
1 Sep 2022to 30 Jan 2027
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult patient with ARDS on VV-ECMO

Who cannot join

  • 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)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Damian Ratano, MD contact

+1 416-340-3601

damian.ratano@chuv.ch

Eddy Fan, MD, PhD contact

+1 416-340-3601

eddy.fan@uhn.ca

Canada1 site, 1 recruiting

  • Toronto General Hospital

    Toronto, Ontario, M5G 2N2

    Eddy Fan, MD-PhD, + 1 416 340 3601, eddy.fan@uhn.ca

    Manuel Tisminestky, MD

    Recruiting

Other trials in Canada

About this study

Official title: 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).

Read the 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

Being tested
Subcutaneous Heparin
Keywords
Extracorporeal membrane oxygenation, Anticoagulation, Thrombosis, Hemorrhage
Medical subject headings
Thrombosis, Hemorrhage

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Subcutaneous HeparinDrug

    Also called Enoxaparin or unfractionated heparin

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

Study groups in NCT04273607
Study groupRoleWhat they receive
No anticoagulationExperimentalParticipants 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
Receives: Drug: Subcutaneous Heparin
Anticoagulation, ECMO standard of careNo interventionParticipants in this arm will receive the standard of care anticoagulation with unfractionated heparin during the course of ECMO.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. ECMO associated thrombotic complications

    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

    Measured: through ECMO completion, an average of 14 days

Secondary outcomes (1)

  1. Hemorrhagic complications

    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

    Measured: through ECMO completion, an average of 14 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Feb 2020
  2. Study start1 Sep 2022
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion30 Jan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04273607
Sponsor's protocol ID
19-5692.0
Acronym
A-FREE ECMO
Status last verified
Jan 2026
First submitted
11 Feb 2020
Last updated
16 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Krueger K, Schmutz A, Zieger B, Kalbhenn J. Venovenous Extracorporeal Membrane Oxygenation With Prophylactic Subcutaneous Anticoagulation Only: An Observational Study in More Than 60 Patients. Artif Organs. 2017 Feb;41(2):186-192. doi: 10.1111/aor.12737. Epub 2016 Jun 3.

    PubMed 27256966

  • Whittlesey GC, Drucker DE, Salley SO, Smith HG, Kundu SK, Palder SB, Klein MD. ECMO without heparin: laboratory and clinical experience. J Pediatr Surg. 1991 Mar;26(3):320-4; discussion 324-5. doi: 10.1016/0022-3468(91)90510-z.

    PubMed 2030479

  • Wen PH, Chan WH, Chen YC, Chen YL, Chan CP, Lin PY. Non-heparinized ECMO serves a rescue method in a multitrauma patient combining pulmonary contusion and nonoperative internal bleeding: a case report and literature review. World J Emerg Surg. 2015 Mar 12;10:15. doi: 10.1186/s13017-015-0006-9. eCollection 2015.

    PubMed 25774211

  • Dornia C, Philipp A, Bauer S, Stroszczynski C, Schreyer AG, Muller T, Koehl GE, Lehle K. D-dimers Are a Predictor of Clot Volume Inside Membrane Oxygenators During Extracorporeal Membrane Oxygenation. Artif Organs. 2015 Sep;39(9):782-7. doi: 10.1111/aor.12460. Epub 2015 Apr 7.

    PubMed 25845704

  • Lubnow M, Philipp A, Dornia C, Schroll S, Bein T, Creutzenberg M, Diez C, Schmid C, Pfeifer M, Riegger G, Muller T, Lehle K. D-dimers as an early marker for oxygenator exchange in extracorporeal membrane oxygenation. J Crit Care. 2014 Jun;29(3):473.e1-5. doi: 10.1016/j.jcrc.2013.12.008. Epub 2013 Dec 30.

    PubMed 24508200

  • Lehle K, Philipp A, Gleich O, Holzamer A, Muller T, Bein T, Schmid C. Efficiency in extracorporeal membrane oxygenation-cellular deposits on polymethylpentene membranes increase resistance to blood flow and reduce gas exchange capacity. ASAIO J. 2008 Nov-Dec;54(6):612-7. doi: 10.1097/MAT.0b013e318186a807.

    PubMed 19033775

  • Sidebotham D, Allen SJ, McGeorge A, Ibbott N, Willcox T. Venovenous extracorporeal membrane oxygenation in adults: practical aspects of circuits, cannulae, and procedures. J Cardiothorac Vasc Anesth. 2012 Oct;26(5):893-909. doi: 10.1053/j.jvca.2012.02.001. Epub 2012 Apr 13. No abstract available.

    PubMed 22503344

  • Lubnow M, Philipp A, Foltan M, Bull Enger T, Lunz D, Bein T, Haneya A, Schmid C, Riegger G, Muller T, Lehle K. Technical complications during veno-venous extracorporeal membrane oxygenation and their relevance predicting a system-exchange--retrospective analysis of 265 cases. PLoS One. 2014 Dec 2;9(12):e112316. doi: 10.1371/journal.pone.0112316. eCollection 2014.

    PubMed 25464516

  • Panigada M, E Iapichino G, Brioni M, Panarello G, Protti A, Grasselli G, Occhipinti G, Novembrino C, Consonni D, Arcadipane A, Gattinoni L, Pesenti A. Thromboelastography-based anticoagulation management during extracorporeal membrane oxygenation: a safety and feasibility pilot study. Ann Intensive Care. 2018 Jan 16;8(1):7. doi: 10.1186/s13613-017-0352-8.

    PubMed 29340875

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Subcutaneous Heparin in people with Extracorporeal Membrane Oxygenation Complication, run by Damian Ratano at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 16 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Damian Ratano, MD (+1 416-340-3601, damian.ratano@chuv.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ECMO associated thrombotic complications (time frame: through ECMO completion, an average of 14 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04273607, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2026.

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