Anticoagulation-free VV ECMO for Acute Respiratory Failure

NCT ID: NCT04273607

Last Updated: 2026-01-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-01
• Study Completion Date: 2027-01-30

Brief 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. 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).

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

Conditions

Extracorporeal Membrane Oxygenation Complication

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Subcutaneous Heparin

Intervention Type: DRUG

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

Anticoagulation, ECMO standard of care

Participants in this arm will receive the standard of care anticoagulation with unfractionated heparin during the course of ECMO.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Subcutaneous Heparin

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

Intervention Type: DRUG

Other Intervention Names

Enoxaparin or unfractionated heparin

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Physicians' Services Incorporated Foundation

OTHER

Sponsor Role: collaborator

Damian Ratano

OTHER

Sponsor Role: lead

Responsible Party

Damian Ratano

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Damian Ratano, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Eddy Fan, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

Toronto General Hospital

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Damian Ratano, MD

Role: CONTACT

damian.ratano@chuv.ch

+1 416-340-3601

Eddy Fan, MD, PhD

Role: CONTACT

eddy.fan@uhn.ca

+1 416-340-3601

Facility Contacts

Eddy Fan, MD-PhD

Role: primary

eddy.fan@uhn.ca

+ 1 416 340 3601

References

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Reference Type: BACKGROUND

PMID: 27256966 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 2030479 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25774211 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 25845704 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24508200 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 19033775 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 22503344 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25464516 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29340875 (View on PubMed)

Other Identifiers

19-5692.0

Identifier Type: -

Identifier Source: org_study_id