A-FREE ECMO: Anticoagulation-free VV ECMO for Acute Respiratory Failure

Sponsor

Damian Ratano (Other)

Overall Status

Recruiting

CT.gov ID

NCT04273607

Collaborator

PSI Foundation, Toronto, Ontario (Other)

Enrollment

Location

Arms

21.9

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Extracorporeal Membrane Oxygenation Complication	Drug: Subcutaneous Heparin	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Jun 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Subcutaneous Heparin The intervention group will receive prophylactic heparin instead of standard of care therapeutic intravenous heparin Other Names: Enoxaparin or unfractionated heparin
No Intervention: Anticoagulation, ECMO standard of care Participants in this arm will receive the standard of care anticoagulation with unfractionated heparin during the course of ECMO.

Arm

Intervention/Treatment

Experimental: 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

Drug: Subcutaneous Heparin

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

Other Names:

Enoxaparin or unfractionated heparin

No Intervention: Anticoagulation, ECMO standard of care

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

Outcome Measures

Primary Outcome Measures

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

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

Other Outcome Measures

Increase in d-dimer levels [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).
Transfusion of blood and blood-derived products related or not to a bleeding event [through ECMO completion, an average of 14 days]
Amount of blood products transfused to patients in each groups during the course of ECMO
Coagulation parameters on ECMO [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)
Amount of clot and fibrin visualized in the pre- and post-membrane side [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)