Anticoagulation-free VV ECMO for Acute Respiratory Failure (A-FREE ECMO)

Damian Ratano

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Extracorporeal Membrane Oxygenation Complication

Treatments: Drug: Subcutaneous Heparin

Study type: Interventional

Funder types: Other

Identifiers

NCT04273607

19-5692.0

Details and patient eligibility

About

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).

Full 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

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

40 participants in 2 patient groups

No anticoagulation

Experimental group

Description:

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

Treatment:

Drug: Subcutaneous Heparin

Anticoagulation, ECMO standard of care

No Intervention group

Description:

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