Antithrombin supplementation during extracorporeal membrane oxygenation: study protocol for a pilot randomized clinical trial

Mauro Panigada, Elena Spinelli, Alberto Cucino, Elisa Cipriani, Stefano De Falco, Giovanna Panarello, Giovanna Occhipinti, Antonio Arcadipane, Gabriele Sales, Vito Fanelli, Luca Brazzi, Cristina Novembrino, Dario Consonni, Antonio Pesenti, Giacomo Grasselli, Mauro Panigada, Elena Spinelli, Alberto Cucino, Elisa Cipriani, Stefano De Falco, Giovanna Panarello, Giovanna Occhipinti, Antonio Arcadipane, Gabriele Sales, Vito Fanelli, Luca Brazzi, Cristina Novembrino, Dario Consonni, Antonio Pesenti, Giacomo Grasselli

Abstract

Background: Normal levels of plasma antithrombin (AT) activity might decrease heparin requirements to achieve an adequate level of anticoagulation during treatment with extracorporeal membrane oxygenation (ECMO). Acquired AT deficiency during ECMO is common, but formal recommendations on target, timing, and rate of AT supplementation are 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: Grifols Antithrombin Research Awards (GATRA) is a 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 and 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 the ratio of activated partial thromboplastin time between 1.5 and 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.

Conflict of interest statement

MP was awarded GATRA Grifols Antithrombin Research Awards in 2016. He received payment and travel support for lectures from Shire® and Werfen® Instrumentation Laboratory. GG received payment for lectures from Pfizer, Getinge, Draeger, and Fisher & Paykel and support for travel/congress activities from Biotest and Getinge (all unrelated to the present manuscript). The other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Intervention and assessment schedule
Fig. 2
Fig. 2
CONSORT flow diagram
Fig. 3
Fig. 3
Protocol for anthithrombin supplementation
Fig. 4
Fig. 4
Anticoagulation protocol

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