Monitoring Anticoagulation in Patients on ECMO for Severe Lung Failure

Monitoring Anticoagulation With Argatroban in Patients on Extracorporeal Membrane Oxygenation for Severe Lung Failure Using Anti-FIIa. Monitoring Anticoagulation With Unfractionated Heparin in Patients on Extracorporeal Membrane Oxygenation for Severe Lung Failure Using Anti-FXa.

A monocentric observational study evaluates the accuracy of anticoagulation monitoring in critically ill patients on ECLS (extracorporeal life support) using new markers of the effect of direct thrombin inhibitors and also the accuracy of anticoagulation monitoring in patients on unfractionated heparin using anti-Xa. A more accurate setting of anticoagulation may lead to a reduction in the number of serious bleeding and thrombotic complications in these patients.

Study Overview

• Status: Completed
• Conditions: COVID-19; ARDS
• Intervention / Treatment: Drug: Argatroban Injection; Drug: Heparin

Detailed Description

Anticoagulation using a direct thrombin inhibitor, argatroban, is one of the modern options for anticoagulation in patients on VV (veno-venous) ECMO (extracorporeal membrane oxygenation) support, and in 2021 the ECMO center of the University Hospital Ostrava changed the standard anticoagulation using UHF (unfractionated heparin) to anticoagulation using Argatroban as a new standard of routine care. Argatroban shows more stable levels and has a short half-life, and a number of foreign ECMO centers have been using Argatroban for a long time also as basic anticoagulation in all ECMO patients.

To monitor the effect of direct thrombin inhibitors, it is possible to use monitoring of anti-FIIa activity, which directly assesses the effect of the anticoagulant on thrombin activity. Anticoagulation with Argatroban may reduce the risk of serious bleeding complications. Target values of aPTT (Activated Partial Thromboplastin Time) and anti-FIIa can be determined according to ELSO (Extracorporeal Life Support Organization) guidelines.

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

• Study Contact: Name: Jiří Hynčica; Phone Number: 2587 0042059737; Email: jiri.hyncica@fno.cz

Study Locations

• Czechia
  • Moravian-Silesian Region
    • Ostrava, Moravian-Silesian Region, Czechia, 70852
      • University Hospital Ostrava

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients on VV (veno-venous) ECMO on anticoagulation with Argatroban or heparin.

Description

Inclusion Criteria:

• Patients with COVID-19
• ARDS according to the Berlin definition
• Veno-venous (VV) ECMO
• Full coagulation with Argatroban or heparin to an anti-FIIa value of 0.4-1.5 or aPTT 50-60

Exclusion Criteria:

- age under 18 years

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Argatroban anticoagulation; Study subjects in this group will receive Argatroban anticoagulation.	Drug: Argatroban Injection; Argatroban will be administered to the study subjects in this group in order to achieve anticoagulation.
Heparin anticoagulation; Study subjects in this group will receive Heparin anticoagulation.	Drug: Heparin; Heparin will be administered to the study subjects in this group in order to achieve anticoagulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of aPTT values with anti-IIa and Argatroban dose in patients on VV ECMO	Comparison of correlation of aPTT and anti-IIa with dynamics of D dimer, FDP (fibrin degradation product) and acute phase reactants of ferritin, CRP (C-reactive protein) Correlation of bleeding complications with aPTT, anti-IIa, platelets	up to 2 weeks
Comparison of apt and anti-Xa values and heparin dose in patients on VV ECMO	Comparison of correlation of aPTT and anti-Xa with dynamics of D dimer, FDP and acute phase reactants of ferritin, CRP	up to 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and severity of bleeding complications	Comparison of frequency and severity of bleeding complications in patients on anticoagulation with Argatroban and heparin	up to 2 weeks
Frequency and severity of thrombotic complications	Comparison of frequency and severity of thrombotic complications in patients anticoagulated with Argatroban and heparin	up to 2 weeks
Consumption of blood products (in ml)	The consumption of blood products (volume in ml) in patients on Argatroban and heparin	up to 2 weeks

Collaborators and Investigators

• Sponsor: University Hospital Ostrava
• Investigators: Principal Investigator: Filip Burša, MD, Ph.D., University Hospital Ostrava

Publications and helpful links

General Publications

• Al-Samkari H, Gupta S, Leaf RK, Wang W, Rosovsky RP, Brenner SK, Hayek SS, Berlin H, Kapoor R, Shaefi S, Melamed ML, Sutherland A, Radbel J, Green A, Garibaldi BT, Srivastava A, Leonberg-Yoo A, Shehata AM, Flythe JE, Rashidi A, Goyal N, Chan L, Mathews KS, Hedayati SS, Dy R, Toth-Manikowski SM, Zhang J, Mallappallil M, Redfern RE, Bansal AD, Short SAP, Vangel MG, Admon AJ, Semler MW, Bauer KA, Hernan MA, Leaf DE; STOP-COVID Investigators. Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19. Ann Intern Med. 2021 May;174(5):622-632. doi: 10.7326/M20-6739. Epub 2021 Jan 26. Erratum In: Ann Intern Med. 2021 Jun;174(6):888.
• Kowalewski M, Fina D, Slomka A, Raffa GM, Martucci G, Lo Coco V, De Piero ME, Ranucci M, Suwalski P, Lorusso R. COVID-19 and ECMO: the interplay between coagulation and inflammation-a narrative review. Crit Care. 2020 May 8;24(1):205. doi: 10.1186/s13054-020-02925-3.
• Godier A, Clausse D, Meslin S, Bazine M, Lang E, Huche F, Cholley B, Hamada SR. Major bleeding complications in critically ill patients with COVID-19 pneumonia. J Thromb Thrombolysis. 2021 Jul;52(1):18-21. doi: 10.1007/s11239-021-02403-9. Epub 2021 Mar 1.
• Gils C, Vinholt PJ, Nybo M. Falsely prolonged activated partial thromboplastin time - a pre- and post-analytical issue. Biochem Med (Zagreb). 2019 Feb 15;29(1):011001. doi: 10.11613/BM.2019.011001. Epub 2018 Dec 15.
• Seelhammer TG, Plack D, Lal A, Nabzdyk CGS. COVID-19 and ECMO: An Unhappy Marriage of Endothelial Dysfunction and Hemostatic Derangements. J Cardiothorac Vasc Anesth. 2020 Dec;34(12):3193-3196. doi: 10.1053/j.jvca.2020.09.132. Epub 2020 Oct 2. No abstract available.
• Alberio L, Angelillo-Scherrer A, Asmis L, Casini A, Fontana P, Graf L, Hegemann I, Kremer Hovinga JA, Korte W, Lecompte T, Martinez M, Nagler M, Studt JD, Tsakiris DA, Wuillemin W. Recommendations on the use of anticoagulants for the treatment of patients with heparin-induced thrombocytopenia in Switzerland. Swiss Med Wkly. 2020 Apr 24;150:w20210. doi: 10.4414/smw.2020.20210. eCollection 2020 Apr 20.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2020
• Primary Completion (Actual): July 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: September 8, 2023
• First Submitted That Met QC Criteria: September 8, 2023
• First Posted (Actual): September 15, 2023

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: ECMO; anticoagulation; Argatroban; ARDS (acute respiratory distress syndrome); thrombotic complications; LMWH (low-molecular-weight heparin)
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Heparin; Argatroban
• Other Study ID Numbers: FNO-KARIM-Argatroban

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No