Anticoagulation-free VV ECMO for Acute Respiratory Failure

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Extracorporeal Membrane Oxygenation Complication

Intervention / Treatment
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* Drug: Subcutaneous Heparin


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: No anticoagulation<br>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<br>* The intervention group will receive prophylactic heparin instead of standard of care therapeutic intravenous heparin<br>* Other names: Enoxaparin or unfractionated heparin;|
| No Intervention: Anticoagulation, ECMO standard of care<br>Participants in this arm will receive the standard of care anticoagulation with unfractionated heparin during the course of ECMO. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | through ECMO completion, an average of 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | through ECMO completion, an average of 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thrombosis, Hemorrhage, Extracorporeal membrane oxygenation, Anticoagulation