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.

Study Overview

• Status: Recruiting
• Conditions: Extracorporeal Membrane Oxygenation Complication; Anticoagulants and Bleeding Disorders
• Intervention / Treatment: Drug: Argatroban; Drug: Unfractionated heparin

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Nina Buchtele, MD, PhD; Phone Number: +431 40400 44900; Email: nina.buchtele@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Thomas Staudinger, Prof MD
    • Contact: Nina Buchtele, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Argatroban; 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; Argatroban is a synthetic, univalent DTI, that directly binds to the catalytic thrombin binding site exerting its effects
Active Comparator: Unfractionated Heparin; 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; Unfractionated heparin produces its major anticoagulant effect by inactivating thrombin and activated factor X (factor Xa) through an antithrombin (AT)-dependent mechanism.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transfusion rate of packed red blood cells assessed as total units/ECMO day	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
Grading of bleeding	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
Mortality rate at day 28/90	assessed by chart review or telephone call	Until 90 days after start of study drug administration

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Thomas Staudinger, MD, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: December 4, 2021
• First Submitted That Met QC Criteria: January 25, 2022
• First Posted (Actual): February 7, 2022

Study Record Updates

• Last Update Posted (Actual): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 14, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Blood Coagulation Disorders; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Heparin; Calcium heparin; Argatroban
• Other Study ID Numbers: Argatroban_ECMO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: upon reasonable request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No