Antithrombin Supplementation during Extracorporeal Membrane Oxygenation: Study Protocol for a Pilot Randomized Clinical Trial

Abstract Background: Normal levels of plasma antithrombin (AT) activity might decrease heparin requirements to achieve anticoagulation target during treatment with extracorporeal membrane oxygenation (ECMO), possibly reducing the risk of bleeding. Acquired AT deficiency during ECMO is common, but formal recommendation on target, timing, and rate of AT supplementation is lacking. Thus, we conceived a pilot trial to evaluate the feasibility and safety of prolonged AT supplementation in patients requiring veno-venous ECMO for respiratory failure. Methods: GATRA is a phase 3, prospective, randomized, single blinded multicenter controlled two-arm trial. Patients undergoing veno-venous ECMO will be randomized to either receive AT supplementation to maintain a functional AT level between 80%-120% (AT supplementation group) or not (control group) for the entire ECMO course. In both study groups anticoagulation will be provided with unfractionated heparin following a standardized protocol. The primary endpoint will be the dose of heparin required to maintain ratio of activated partial thromboplastin time between 1.5-2. Secondary endpoints will be the adequacy of anticoagulation and the incidence of hemorrhagic and thrombotic complications. Discussion: GATRA is a pilot trial that will test the efficacy of a protocol of AT supplementation in decreasing the heparin dose and improving anticoagulation adequacy during ECMO. If positive, it might provide the basis for a future larger trial aimed at verifying the impact of AT supplementation on a composite outcome endpoint including hemorrhagic events, transfusion requirements and mortality. Trial registration: ClinicalTrials.gov, NCT03208270. Registered on 5 July 2017.