xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06038682</url>
    </required_header>
    <id_info>
      <org_study_id>FNO-KARIM-Argatroban</org_study_id>
      <nct_id>NCT06038682</nct_id>
    </id_info>
    <brief_title>Monitoring Anticoagulation in Patients on ECMO for Severe Lung Failure</brief_title>
    <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.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Hospital Ostrava</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University Hospital Ostrava</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        A monocentric observational study evaluates the accuracy of anticoagulation monitoring in&#xD;
        critically ill patients on ECLS (extracorporeal life support) using new markers of the effect&#xD;
        of direct thrombin inhibitors and also the accuracy of anticoagulation monitoring in patients&#xD;
        on unfractionated heparin using anti-Xa. A more accurate setting of anticoagulation may lead&#xD;
        to a reduction in the number of serious bleeding and thrombotic complications in these&#xD;
        patients.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Anticoagulation using a direct thrombin inhibitor, argatroban, is one of the modern options&#xD;
        for anticoagulation in patients on VV (veno-venous) ECMO (extracorporeal membrane&#xD;
        oxygenation) support, and in 2021 the ECMO center of the University Hospital Ostrava changed&#xD;
        the standard anticoagulation using UHF (unfractionated heparin) to anticoagulation using&#xD;
        Argatroban as a new standard of routine care. Argatroban shows more stable levels and has a&#xD;
        short half-life, and a number of foreign ECMO centers have been using Argatroban for a long&#xD;
        time also as basic anticoagulation in all ECMO patients.&#xD;
  &#xD;
        To monitor the effect of direct thrombin inhibitors, it is possible to use monitoring of&#xD;
        anti-FIIa activity, which directly assesses the effect of the anticoagulant on thrombin&#xD;
        activity. Anticoagulation with Argatroban may reduce the risk of serious bleeding&#xD;
        complications. Target values of aPTT (Activated Partial Thromboplastin Time) and anti-FIIa&#xD;
        can be determined according to ELSO (Extracorporeal Life Support Organization) guidelines.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">June 1, 2021</start_date>
    <completion_date type="Anticipated">June 2024</completion_date>
    <primary_completion_date type="Anticipated">May 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Only</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Comparison of aPTT values with anti-IIa and Argatroban dose in patients on VV ECMO</measure>
      <time_frame>up to 2 weeks</time_frame>
      <description>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</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Comparison of apt and anti-Xa values and heparin dose in patients on VV ECMO</measure>
      <time_frame>up to 2 weeks</time_frame>
      <description>Comparison of correlation of aPTT and anti-Xa with dynamics of D dimer, FDP and acute phase reactants of ferritin, CRP</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Frequency and severity of bleeding complications</measure>
      <time_frame>up to 2 weeks</time_frame>
      <description>Comparison of frequency and severity of bleeding complications in patients on anticoagulation with Argatroban and heparin</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Frequency and severity of thrombotic complications</measure>
      <time_frame>up to 2 weeks</time_frame>
      <description>Comparison of frequency and severity of thrombotic complications in patients anticoagulated with Argatroban and heparin</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Consumption of blood products</measure>
      <time_frame>up to 2 weeks</time_frame>
      <description>Consumption of blood products in patients on Argatroban and heparin</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">100</enrollment>
    <condition>ARDS</condition>
    <condition>COVID-19</condition>
    <arm_group>
      <arm_group_label>Argatroban anticoagulation</arm_group_label>
      <description>Study subjects in this group will receive Argatroban anticoagulation.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Heparin anticoagulation</arm_group_label>
      <description>Study subjects in this group will receive Heparin anticoagulation.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Argatroban Injection</intervention_name>
      <description>Argatroban will be administered to the study subjects in this group in order to achieve anticoagulation.</description>
      <arm_group_label>Argatroban anticoagulation</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Heparin</intervention_name>
      <description>Heparin will be administered to the study subjects in this group in order to achieve anticoagulation.</description>
      <arm_group_label>Heparin anticoagulation</arm_group_label>
    </intervention>
    <biospec_retention>Samples Without DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Blood samples will be obtained from patients in course of the routine care.&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Patients on VV (veno-venous) ECMO on anticoagulation with Argatroban or heparin.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients with COVID-19&#xD;
  &#xD;
            -  ARDS according to the Berlin definition&#xD;
  &#xD;
            -  Veno-venous (VV) ECMO&#xD;
  &#xD;
            -  Full coagulation with Argatroban or heparin to an anti-FIIa value of 0.4-1.5 or aPTT&#xD;
               50-60&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          - age under 18 years&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
    </eligibility>
    <overall_official>
      <last_name>Filip Burša, MD, Ph.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>University Hospital Ostrava</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jiří Hynčica</last_name>
      <phone>0042059737</phone>
      <phone_ext>2587</phone_ext>
      <email>jiri.hyncica@fno.cz</email>
    </overall_contact>
    <location>
      <facility>
        <name>University Hospital Ostrava</name>
        <address>
          <city>Ostrava</city>
          <state>Moravian-Silesian Region</state>
          <zip>70852</zip>
          <country>Czechia</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Jiří Hynčica</last_name>
        <phone>0042059737</phone>
        <phone_ext>2587</phone_ext>
        <email>jiri.hyncica@fno.cz</email>
      </contact>
      <investigator>
        <last_name>Filip Burša, MD,PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Jan Máca, Assoc.Prof.,MD,PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Czechia</country>
    </location_countries>
    <reference>
      <citation>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.</citation>
      <PMID>33493012</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>32384917</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>33646501</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>30591818</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>33228917</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>32329806</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 8, 2023</study_first_submitted>
    <study_first_submitted_qc>September 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 15, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>ECMO</keyword>
    <keyword>ARDS (acute respiratory distress syndrome)</keyword>
    <keyword>anticoagulation</keyword>
    <keyword>thrombotic complications</keyword>
    <keyword>LMWH (low-molecular-weight heparin)</keyword>
    <keyword>Argatroban</keyword>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Heparin</mesh_term>
      <mesh_term>Argatroban</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06038682
  org study id: FNO-KARIM-Argatroban
  nct id: NCT06038682
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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.
  observational model: Case-Only
  time perspective: Prospective
  measure: Comparison of aPTT values with anti-IIa and Argatroban dose in patients on VV ECMO
  time frame: up to 2 weeks
  description: 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
  measure: Comparison of apt and anti-Xa values and heparin dose in patients on VV ECMO
  time frame: up to 2 weeks
  description: Comparison of correlation of aPTT and anti-Xa with dynamics of D dimer, FDP and acute phase reactants of ferritin, CRP
  measure: Frequency and severity of bleeding complications
  time frame: up to 2 weeks
  description: Comparison of frequency and severity of bleeding complications in patients on anticoagulation with Argatroban and heparin
  measure: Frequency and severity of thrombotic complications
  time frame: up to 2 weeks
  description: Comparison of frequency and severity of thrombotic complications in patients anticoagulated with Argatroban and heparin
  measure: Consumption of blood products
  time frame: up to 2 weeks
  description: Consumption of blood products in patients on Argatroban and heparin
  arm group label: Argatroban anticoagulation
  description: Study subjects in this group will receive Argatroban anticoagulation.
  arm group label: Heparin anticoagulation
  description: Study subjects in this group will receive Heparin anticoagulation.
  intervention type: Drug
  intervention name: Argatroban Injection
  description: Argatroban will be administered to the study subjects in this group in order to achieve anticoagulation.
  arm group label: Argatroban anticoagulation
  intervention type: Drug
  intervention name: Heparin
  description: Heparin will be administered to the study subjects in this group in order to achieve anticoagulation.
  arm group label: Heparin anticoagulation
  Blood samples will be obtained from patients in course of the routine care.
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  last name: Filip Burša, MD, Ph.D.
  role: Principal Investigator
  affiliation: University Hospital Ostrava
  last name: Jiří Hynčica
  phone: 0042059737
  phone ext: 2587
  email: jiri.hyncica@fno.cz
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  investigator: 
  country: Czechia
  citation: 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.
  PMID: 33493012
  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.
  PMID: 32384917
  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.
  PMID: 33646501
  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.
  PMID: 30591818
  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.
  PMID: 33228917
  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.
  PMID: 32329806
  responsible party type: Sponsor
  mesh term: Heparin
  mesh term: Argatroban