Monitoring Anticoagulation in Patients on ECMO for Severe Lung Failure

• ClinicalTrials.gov Identifier: NCT06038682
• Recruitment Status: Completed
• First Posted: September 15, 2023
• Last Update Posted: March 1, 2024
• Sponsor: University Hospital Ostrava
• Information provided by (Responsible Party): University Hospital Ostrava

Tracking Information

• First Submitted Date: September 8, 2023
• First Posted Date: September 15, 2023
• Last Update Posted Date: March 1, 2024
• Actual Study Start Date: April 1, 2020
• Actual Primary Completion Date: July 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 8, 2023)

• Comparison of aPTT values with anti-IIa and Argatroban dose in patients on VV ECMO [ Time Frame: up to 2 weeks ]
  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
• Comparison of apt and anti-Xa values and heparin dose in patients on VV ECMO [ Time Frame: up to 2 weeks ]
  Comparison of correlation of aPTT and anti-Xa with dynamics of D dimer, FDP and acute phase reactants of ferritin, CRP

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 18, 2023)

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

Original Secondary Outcome Measures (submitted: September 8, 2023)

• Frequency and severity of bleeding complications [ Time Frame: up to 2 weeks ]
  Comparison of frequency and severity of bleeding complications in patients on anticoagulation with Argatroban and heparin
• Frequency and severity of thrombotic complications [ Time Frame: up to 2 weeks ]
  Comparison of frequency and severity of thrombotic complications in patients anticoagulated with Argatroban and heparin
• Consumption of blood products [ Time Frame: up to 2 weeks ]
  Consumption of blood products in patients on Argatroban and heparin

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Monitoring Anticoagulation in Patients on ECMO for Severe Lung Failure
• 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.
• Brief 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.

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
• Study Design: Observational Model: Case-Only; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

Blood samples will be obtained from patients in course of the routine care.

• Sampling Method: Non-Probability Sample
• Study Population: Patients on VV (veno-venous) ECMO on anticoagulation with Argatroban or heparin.

Condition

• ARDS
• COVID-19

Intervention

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

Study Groups/Cohorts

• Argatroban anticoagulation
  Study subjects in this group will receive Argatroban anticoagulation.
  Intervention: Drug: Argatroban Injection
• Heparin anticoagulation
  Study subjects in this group will receive Heparin anticoagulation.
  Intervention: Drug: Heparin

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 8, 2023): 100
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 31, 2023
• Actual Primary Completion Date: July 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Not Provided
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Czechia

Administrative Information

• NCT Number: NCT06038682
• Other Study ID Numbers: FNO-KARIM-Argatroban
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University Hospital Ostrava
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital Ostrava
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: University Hospital Ostrava
• Verification Date: February 2024