TY - JOUR
T1 - Antithrombin supplementation during extracorporeal membrane oxygenation
T2 - study protocol for a pilot randomized clinical trial
AU - Panigada, Mauro
AU - Spinelli, Elena
AU - Cucino, Alberto
AU - Cipriani, Elisa
AU - De Falco, Stefano
AU - Panarello, Giovanna
AU - Occhipinti, Giovanna
AU - Arcadipane, Antonio
AU - Sales, Gabriele
AU - Fanelli, Vito
AU - Brazzi, Luca
AU - Novembrino, Cristina
AU - Consonni, Dario
AU - Pesenti, Antonio
AU - Grasselli, Giacomo
PY - 2019/6/11
Y1 - 2019/6/11
N2 - 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.
AB - 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.
KW - Adult
KW - Antithrombins/administration & dosage
KW - Dietary Supplements
KW - Extracorporeal Membrane Oxygenation/methods
KW - Humans
KW - Pilot Projects
KW - Prospective Studies
KW - Randomized Controlled Trials as Topic
KW - Respiratory Insufficiency/therapy
KW - Single-Blind Method
U2 - 10.1186/s13063-019-3386-4
DO - 10.1186/s13063-019-3386-4
M3 - Article
C2 - 31186035
VL - 20
SP - 349
JO - Trials
JF - Trials
SN - 1745-6215
IS - 1
ER -