Safety and Feasibility of Argatroban as Anticoagulant in Adults With ECMO

A Prospective Randomized Pilot Trial on Safety and Feasibility of Argatroban as Anticoagulant in Patients With Extracorporeal Membrane Oxygenation (ECMO)

This prospective, randomized, controlled pilot trial aims to assess the safety and feasibility of Argatroban as an alternative anticoagulant to unfractionated heparin in patients receiving extracorporeal membrane oxygenation.

Continuous infusion of 0,3μg/kg/min to target an aPTT of 50-70sec and/or Hemoclot of 0,60 - 0,80 µg/mL

Continuous infusion of Unfractionated Heparin to target an aPTT of 50-60 seconds and/or Anti-Xa level between 0.20 and 0.30 IU/ml and/or thrombin time >20sec.

Argatroban is a synthetic, univalent DTI, that directly binds to the catalytic thrombin binding site exerting its effects

Unfractionated heparin produces its major anticoagulant effect by inactivating thrombin and activated factor X (factor Xa) through an antithrombin (AT)-dependent mechanism.

Bleeding will be assessed continuously by the investigators according to the BARC bleeding classification, where bleeding type 2 or higher will be considered as clinically significant bleeding; outcome measures will be the incidence of clinically significant bleeding per ECMO day and time to first bleeding; thrombosis is defined as any occurence of thromboembolism including membrane lung exchange due to suspected thrombosis, pulmonary embolism or deep vein thrombosis; outcome measures will be the incidence of thromboembolism per ECMO day and the time to first thromboembolism

From date of randomization until the date of ECMO discontinuation, or death, whichever came first, assessed up to 120 days

study enrollment, study completion and ability to achieve target values of Argatroban as anticoagulant in ECMO

ratio of screened to included patients, proportion of patients who completed the study according to the protocol, proportion of coagulation tests within range and total number of dose adjustments

From date of randomization until the date of ECMO discontinuation, or death, whichever came first, assessed up to 120 days

Assessment of the total amount of units (250-300ml each) packed red blood cells transfused per ECMO day following a transfusion threshold of Hb<8g/dl

From date of randomization until the date of ECMO discontinuation, or death, whichever came first, assessed up to 120 days

According to the Bleeding Academic Research Consortium type 1 - 5 (Type 1: Bleeding that is not actionable; Type 2: Any clinically overt sign of hemorrhage that "is actionable" and requires diagnostic studies, hospitalization, or treatment by a health care professional; Type 3a. Overt bleeding plus hemoglobin drop of 3 to < 5 g/dL (provided hemoglobin drop is related to bleed); transfusion with overt bleeding; Type 3b. Overt bleeding plus hemoglobin drop < 5 g/dL (provided hemoglobin drop is related to bleed); cardiac tamponade; bleeding requiring surgical intervention for control; bleeding requiring IV vasoactive agents; type 3c. Intracranial hemorrhage confirmed by autopsy, imaging, or lumbar puncture; intraocular bleed compromising vision; Type 4: CABG-related bleeding within 48 hours; Type 5a. Probable fatal bleeding; Type 5b. Definite fatal bleeding (overt or autopsy or imaging confirmation)

From date of randomization until the date of ECMO discontinuation, or death, whichever came first, assessed up to 120 days

Inclusion Criteria: Minimum Age 18 years VV- or VA-ECMO therapy Minimum of 24h planned ECMO-therapy Exclusion Criteria: History of Heparin-induced thrombocytopenia (HIT) High risk of bleeding, contraindication for anticoagulation (eg. active GI-bleeding, Intracerebral bleeding; Platelet count <50G/l, congenital bleeding disorder) Pregnancy Severe Liver disease (SOFA score liver domain 4 points = Bilirubin >12mg/dl) Postoperative admission Strong lupus anticoagulant or acquired intrinsic clotting factor deficiency at admission (APTT >50 sec without anticoagulation).