Safety and Feasibility of Argatroban as Anticoagulant in Adults With ECMO

Study Overview
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Brief Summary
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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.

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

Conditions
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Extracorporeal Membrane Oxygenation Complication, Anticoagulants and Bleeding Disorders

Intervention / Treatment
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* Drug: Argatroban
* Drug: Unfractionated heparin


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomization ratio of 1:1 for anticoagulation with Argatroban or Unfractionated Heparin
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Argatroban<br>Continuous infusion of 0,3μg/kg/min to target an aPTT of 50-70sec and/or Hemoclot of 0,60 - 0,80 µg/mL | Drug: Argatroban<br>* Argatroban is a synthetic, univalent DTI, that directly binds to the catalytic thrombin binding site exerting its effects<br>|
| Active Comparator: Unfractionated Heparin<br>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. | Drug: Unfractionated heparin<br>* Unfractionated heparin produces its major anticoagulant effect by inactivating thrombin and activated factor X (factor Xa) through an antithrombin (AT)-dependent mechanism.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding and thrombosis with Argatroban compared to unfractionated Heparin (UFH) | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |