Monitoring Anticoagulation in Patients on ECMO for Severe Lung Failure

COVID-19 Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06038682
• Other study ID #: FNO-KARIM-Argatroban
• Status: Completed
• Start date: April 1, 2020
• Est. completion date: December 31, 2023

Study information

• Verified date: February 2024
• Source: University Hospital Ostrava
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: December 31, 2023
• Est. primary completion date: July 31, 2023
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• ARDS
• COVID-19

Intervention

Drug:
• Argatroban Injection
Argatroban will be administered to the study subjects in this group in order to achieve anticoagulation.
• Heparin
Heparin will be administered to the study subjects in this group in order to achieve anticoagulation.

Locations

Country	Name	City	State
Czechia	University Hospital Ostrava	Ostrava	Moravian-Silesian Region

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Ostrava

Country where clinical trial is conducted

Czechia, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	Consumption of blood products (in ml)	The consumption of blood products (volume in ml) in patients on Argatroban and heparin	up to 2 weeks