Comparing Anticoagulation Strategies Using UFH, Argatroban and LMWH for ECMO Support (CASUAL-ECMO)

A Three-arm Randomized Controlled Non-inferiority Pilot Study Comparing Anticoagulation Strategies Using Unfractionated Heparin, Argatroban and Low-molecular-weight Heparin for Extracorporeal Membrane Oxygenation Support

A three-arm randomized controlled non-inferiority pilot study comparing anticoagulation strategies using unfractionated heparin, argatroban and enoxaparin for extracorporeal membrane oxygenation support conducted as an investigator-initiated, prospective, parallel group, open-label, active comparator controlled, single center, phase IV study to evaluate the non-inferiority of enoxaparin or argatroban for anticoagulation during ECMO therapy in comparison to the current standard, unfractionated heparin, as measured by the incidence of thromboembolic events during the duration of ECMO therapy

Study Overview

• Status: Recruiting
• Conditions: Respiratory Insufficiency; Bleeding; Thromboembolism; Circulatory Failure
• Intervention / Treatment: Drug: Enoxaparin Injectable Solution; Drug: Argatroban, 1 Mg/mL Intravenous Solution; Drug: Unfractionated heparin

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Vincenz Scharner, MD; Phone Number: 4100 +43 1 40400; Email: vincenz.scharner@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Vincenz Scharner, Dr. med.; Email: vincenz.scharner@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• either

  • require ECMO support or
  • have been started on ECMO therapy within the last 12 hours

Exclusion Criteria:

• Patients exhibiting contraindications to anticoagulation in general or any of the three investigated substances
• Patients who are pregnant
• Patients suffering from a clinically relevant pre-existing coagulopathy
• Patients, for whom screening, randomization and implementation of study protocol cannot be initiated within 12 hours after cannulation
• Patients receiving ongoing therapeutic systemic anticoagulation prior to ECMO implantation, or exhibiting an indication for therapeutic anticoagulation (e.g., pulmonary embolism)
• Patients whose total duration of ECMO support lasts less than 24 hours
• Patients with start of ECMO support during CPR (eCPR)
• Patients with passive decarboxylation, without an active pumping system
• Patients, who have been weaned off ECMO support within the last 30 days
• Patients with central ECMO cannulation and/or after cardiopulmonary bypass

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enoxaparin group; Anticoagulation for the duration of the study will be conducted using subcutaneous Enoxaparin	Drug: Enoxaparin Injectable Solution; Subcutaneous Enoxaparin will be dosed at 0.5 mg/kg twice daily
Experimental: Argatroban group; Anticoagulation for the duration of the study will be conducted using intravenous Argatroban.	Drug: Argatroban, 1 Mg/mL Intravenous Solution; Intravenous Argatroban will be administered as a continuous infusion of 0.1-1 µg/kg/min with a target modified thrombin time measured using Hemoclot of 0,40 - 0,60 µg/mL.
Active Comparator: Unfractionated heparin group; Anticoagulation for the duration of the study will be conducted using intravenous unfractionated heparin	Drug: Unfractionated heparin; Unfractionated heparin will be administered as a continuous infusion of 7.5-20 units/kg/h with a target Anti FXa calibrated for UFH of 0.3-0.5 u/mL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of thromboembolic events during ECMO therapy	Clinically relevant thromboembolic events (Clinical suspicion; confirmation via imaging); Pulmonary embolism, deep vein thrombosis; Intracardiac thrombosis; Arterial thromboembolism including myocardial and cerebral infarction; Deep vein thrombosis (detected during daily routine sonography); Need to exchange ECMO circuit due to acute or incipient clotting	through duration of the ECMO run; an average of 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding events	Incidence of bleeding events classified according to BARC Criteria	through duration of the ECMO run; an average of 14 days

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Johannes Gratz, PD, MD, PhD, Medical Univeristy of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2024
• Primary Completion (Estimated): January 30, 2027
• Study Completion (Estimated): July 30, 2027

Study Registration Dates

• First Submitted: May 27, 2024
• First Submitted That Met QC Criteria: June 2, 2024
• First Posted (Actual): June 4, 2024

Study Record Updates

• Last Update Posted (Actual): October 29, 2024
• Last Update Submitted That Met QC Criteria: October 26, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Anticoagulation; anticoagulant; ECMO; Bleeding; heparin; extracorporeal life support; Thromboembolic Event
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Embolism and Thrombosis; Respiratory Insufficiency; Thromboembolism; Shock; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Fibrin Modulating Agents; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Anticoagulants; Antithrombins; Serine Proteinase Inhibitors; Enoxaparin; Pharmaceutical Solutions; Heparin; Calcium heparin; Argatroban
• Other Study ID Numbers: 1644/2022

Drug and device information, study documents

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