Anticoagulation-free VV ECMO for Acute Respiratory Failure

Phase 2

• Conditions: Extracorporeal Membrane Oxygenation Complication
• Interventions: Drug: Subcutaneous Heparin

• Registration Number: NCT04273607
• Lead Sponsor: Damian Ratano

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

Study Timeline

• Study First Submitted: 2020-02-11
• Study First Submitted QC: 2020-02-13
• Study First Posted: 2020-02-18
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-19
• Last Update Posted: 2022-08-24
• Study Start: 2022-09-01
• Primary Completion: 2023-12-31
• Study Completion: 2024-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
No anticoagulation	Subcutaneous Heparin	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

Primary Outcome Measures

Name	Time	Method
ECMO associated thrombotic complications	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 Outcome Measures

Name	Time	Method
Hemorrhagic complications	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

Trial Locations

Locations (1)

Toronto General Hospital; 🇨🇦 Toronto, Ontario, Canada