Clinical trial NCT04273607: Anticoagulation-free VV ECMO for Acute Respiratory Failure
Official title: Anticoagulation-free VV ECMO for Acute Respiratory Failure: A Pilot Safety and Feasibility Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Extracorporeal Membrane Oxygenation Complication
Keywords: Extracorporeal membrane oxygenation
Anticoagulation
Thrombosis
Hemorrhage
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: PSI Foundation, Toronto, Ontario
First posted: 2020-02-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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)

Primary outcomes:
measure: ECMO associated thrombotic complications
timeFrame: through ECMO completion, an average of 14 days
Secondary outcomes:
measure: Hemorrhagic complications
timeFrame: through ECMO completion, an average of 14 days
Other outcomes:
measure: Increase in d-dimer levels
timeFrame: through ECMO completion, an average of 14 days
measure: Transfusion of blood and blood-derived products related or not to a bleeding event
timeFrame: through ECMO completion, an average of 14 days
measure: Coagulation parameters on ECMO
timeFrame: through ECMO completion, an average of 14 days
measure: Amount of clot and fibrin visualized in the pre- and post-membrane side
timeFrame: through ECMO completion, an average of 14 days
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Damian Ratano, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Health Network, Toronto
name: Eddy Fan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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