<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/NCT01734252</url>
  </required_header>
  <id_info>
    <org_study_id>ArgHeR</org_study_id>
    <nct_id>NCT01734252</nct_id>
  </id_info>
  <brief_title>Argatroban in Critically Ill Patients With Heparin Resistance</brief_title>
  <official_title>A Pilot Trial to Assess the Efficacy of Argatroban (Argatra®) in Critically Ill Patients With Heparin Resistance</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University Innsbruck</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University Innsbruck</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Critically ill patients with high risk for thrombosis or tromboembolic events with the&#xD;
      presence of heparin resistance, treated at the Department for General and Surgical Critical&#xD;
      Care Medicine of the Medical University Innsbruck, Austria will be enrolled in the study when&#xD;
      meeting the inclusion- and exclusion criteria. If a patient meets the inclusion criteria and&#xD;
      is recruited for the study, the patient will be randomized either to Group A or Group H.&#xD;
&#xD;
      All patients have to achieve a prophylactic aPTT-target range of an aPTT-level of 45 - 60 sec&#xD;
      (Pathromtin® SL) within 6 to 8 hours.&#xD;
&#xD;
      Randomisation Group A:&#xD;
&#xD;
      If a Heparin resistance appears and the patient meets the inclusion and exclu-sion criteria,&#xD;
      he/she will be enrolled. The Heparin administration will be stopped and Argatroban will be&#xD;
      given and adjusted until the target aPTT-range is achieved.&#xD;
&#xD;
      Randomisation Group H - Standard therapy:&#xD;
&#xD;
      If a Heparin resistance appears and the patient meets the inclusion and exclu-sion criteria,&#xD;
      he/she will be enrolled. The Heparin administration will be contin-ued and, if necessary&#xD;
      increased. Hereby the maximum heparin dose is 1.500 IU per hour.&#xD;
&#xD;
      Therapy failure Group H:&#xD;
&#xD;
      Primary target failure at Visit 3 (6-8 hours):&#xD;
&#xD;
      If a patient of Group H does not achieve the target-aPTT within 6-8 hours, he/she will switch&#xD;
      to Group A and will start with T1 (Baseline) and will follow the visits according to Group A&#xD;
      until the final Visit 9 (T1 / day 30).&#xD;
&#xD;
      Maintenance failure after Visit 3:&#xD;
&#xD;
      Maintenance failure after 6-8 hours is defined as non-maintenance of the tar-get-aPTT until&#xD;
      day 7 with a max. heparin dosage of 1.500 IU per hour. In this case, heparin therapy has to&#xD;
      be changed to Argatroban.&#xD;
&#xD;
      The patient will start with T1 (Baseline) and will follow the visits according to Group A&#xD;
      until the final Visit 9 (day 30) counting from the Baseline of Group A.&#xD;
&#xD;
      Therapy failure Group A:&#xD;
&#xD;
      If a patient of Group A does not achieve the target-aPTT within 6-8 hours or cannot maintain&#xD;
      the target-aPTT in spite of reaching the maximum dosage of 10µg/kg/min during the further&#xD;
      study period, the patient automatically drops out of the study.&#xD;
&#xD;
      The same is effective for patients who switched to the Group A after a therapy failure in&#xD;
      Group H.&#xD;
&#xD;
      General:&#xD;
&#xD;
      Two hours after starting the Baseline investigations, patient's parameters in-cluding blood&#xD;
      collections will be measured for the second time (T2). Additional measurements will be made&#xD;
      at 6-8 hours (T3), 24 hours (T4), 48 hours (T5), 5 days (T6) after start of study drug and on&#xD;
      day 7 before (T7) stop of study medication and 6h (T8) after stop of study medication. 30&#xD;
      days after inclusion in the study, a final investigation is planned (T9).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 29, 2012</start_date>
  <completion_date type="Actual">April 1, 2016</completion_date>
  <primary_completion_date type="Actual">April 1, 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of patients who achieved the prophylactic aPTT-range within 6 - 8 hours (Visit 3).</measure>
    <time_frame>The average period for the measurement (aPTT) of the primary outcome is 7 hours. Timepoints of measurements are at Baseline (hour 0) and after 6-8 hours.</time_frame>
    <description>The primary measure is to achieve a prophylactic anticoagulation level within 7(+/-1) hours after Baseline. The parameter to define the anticoagulation level is aPTT and will be measured at 7(+/-1) hours.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Achievement of a Sufficient Thrombosis Prohpylaxis in Clitically Ill Patients With Heparin Resistance</condition>
  <arm_group>
    <arm_group_label>Standard Treatment</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>If a Heparin resistance appears and the patient meets the inclusion and exclu-sion criteria, he/she will be enrolled. The Heparin administration will be contin-ued and, if necessary increased. Hereby the maximum heparin dose is 1.500 IU per hour.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment with Argatroban</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>If a Heparin resistance appears and the patient meets the inclusion and exclu-sion criteria, he/she will be enrolled. The Heparin administration will be stopped and Argatroban will be given and adjusted until the target aPTT-range is achieved.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Argatroban</intervention_name>
    <description>Start: Argatroban dose is 0.05 µg/kg/min (patients with hepatic impairment, after cardiac surgery) until maximum: 10 µg/kg/min</description>
    <arm_group_label>Treatment with Argatroban</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient at risk for thrombosis or thromboembolic complications with the need of&#xD;
             prophylactic antithrombotic therapy&#xD;
&#xD;
          -  Age: 18 - 85 years&#xD;
&#xD;
          -  Prohylactic anticoagulation (aPTT: 45 - 60 sec) is not achieved with a heparin dosage&#xD;
             of 1.200 IU per hour after two hours of infusion&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  If patient needs an aPTT-level &gt; 60 sec for any reason&#xD;
&#xD;
          -  Active bleeding&#xD;
&#xD;
          -  Risk for bleeding higher than risk of thromboembolic event as anticipated by the&#xD;
             physician&#xD;
&#xD;
          -  Surgical procedure with the need for interruption of antithrombotic therapy within the&#xD;
             next 24 hours&#xD;
&#xD;
          -  Inevitable lethal course&#xD;
&#xD;
          -  Severe Liver failure: Quick &lt; 30 %&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Planned peridural or spinal anaesthesia during the study&#xD;
&#xD;
          -  Patient with known refusal of a participation in this clinical trial&#xD;
&#xD;
          -  Active participation in another clinical trial&#xD;
&#xD;
          -  Any condition, including the presence of laboratory abnormalities, which would place&#xD;
             the subject at unacceptable risk if he/she were to participate in the study or&#xD;
             confound the ability to interpret data from the study&#xD;
&#xD;
          -  Any serious medical condition, laboratory abnormality, or psychiatric illness that&#xD;
             would prevent the subject from signing the informed consent form&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Medical University Innsbruck / Department for General and Surgical Intensive Care Medicine</name>
      <address>
        <city>Innsbruck</city>
        <zip>6020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>November 21, 2012</study_first_submitted>
  <study_first_submitted_qc>November 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <last_update_submitted>November 14, 2017</last_update_submitted>
  <last_update_submitted_qc>November 14, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 17, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University Innsbruck</investigator_affiliation>
    <investigator_full_name>Dietmar Fries, M.D.</investigator_full_name>
    <investigator_title>Coordinating and Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Argatroban</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT01734252
org study id: ArgHeR
nct id: NCT01734252
lead sponsor: 
has dmc: Yes
Critically ill patients with high risk for thrombosis or tromboembolic events with the
      presence of heparin resistance, treated at the Department for General and Surgical Critical
      Care Medicine of the Medical University Innsbruck, Austria will be enrolled in the study when
      meeting the inclusion- and exclusion criteria. If a patient meets the inclusion criteria and
      is recruited for the study, the patient will be randomized either to Group A or Group H.

      All patients have to achieve a prophylactic aPTT-target range of an aPTT-level of 45 - 60 sec
      (Pathromtin® SL) within 6 to 8 hours.

      Randomisation Group A:

      If a Heparin resistance appears and the patient meets the inclusion and exclu-sion criteria,
      he/she will be enrolled. The Heparin administration will be stopped and Argatroban will be
      given and adjusted until the target aPTT-range is achieved.

      Randomisation Group H - Standard therapy:

      If a Heparin resistance appears and the patient meets the inclusion and exclu-sion criteria,
      he/she will be enrolled. The Heparin administration will be contin-ued and, if necessary
      increased. Hereby the maximum heparin dose is 1.500 IU per hour.

      Therapy failure Group H:

      Primary target failure at Visit 3 (6-8 hours):

      If a patient of Group H does not achieve the target-aPTT within 6-8 hours, he/she will switch
      to Group A and will start with T1 (Baseline) and will follow the visits according to Group A
      until the final Visit 9 (T1 / day 30).

      Maintenance failure after Visit 3:

      Maintenance failure after 6-8 hours is defined as non-maintenance of the tar-get-aPTT until
      day 7 with a max. heparin dosage of 1.500 IU per hour. In this case, heparin therapy has to
      be changed to Argatroban.

      The patient will start with T1 (Baseline) and will follow the visits according to Group A
      until the final Visit 9 (day 30) counting from the Baseline of Group A.

      Therapy failure Group A:

      If a patient of Group A does not achieve the target-aPTT within 6-8 hours or cannot maintain
      the target-aPTT in spite of reaching the maximum dosage of 10µg/kg/min during the further
      study period, the patient automatically drops out of the study.

      The same is effective for patients who switched to the Group A after a therapy failure in
      Group H.

      General:

      Two hours after starting the Baseline investigations, patient's parameters in-cluding blood
      collections will be measured for the second time (T2). Additional measurements will be made
      at 6-8 hours (T3), 24 hours (T4), 48 hours (T5), 5 days (T6) after start of study drug and on
      day 7 before (T7) stop of study medication and 6h (T8) after stop of study medication. 30
      days after inclusion in the study, a final investigation is planned (T9).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of patients who achieved the prophylactic aPTT-range within 6 - 8 hours (Visit 3).
time frame: The average period for the measurement (aPTT) of the primary outcome is 7 hours. Timepoints of measurements are at Baseline (hour 0) and after 6-8 hours.
description: The primary measure is to achieve a prophylactic anticoagulation level within 7(+/-1) hours after Baseline. The parameter to define the anticoagulation level is aPTT and will be measured at 7(+/-1) hours.
arm group label: Standard Treatment
arm group type: No Intervention
description: If a Heparin resistance appears and the patient meets the inclusion and exclu-sion criteria, he/she will be enrolled. The Heparin administration will be contin-ued and, if necessary increased. Hereby the maximum heparin dose is 1.500 IU per hour.
arm group label: Treatment with Argatroban
arm group type: Experimental
description: If a Heparin resistance appears and the patient meets the inclusion and exclu-sion criteria, he/she will be enrolled. The Heparin administration will be stopped and Argatroban will be given and adjusted until the target aPTT-range is achieved.
intervention type: Drug
intervention name: Argatroban
description: Start: Argatroban dose is 0.05 µg/kg/min (patients with hepatic impairment, after cardiac surgery) until maximum: 10 µg/kg/min
arm group label: Treatment with Argatroban
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
facility: 
country: Austria
responsible party type: Principal Investigator
investigator affiliation: Medical University Innsbruck
investigator full name: Dietmar Fries, M.D.
investigator title: Coordinating and Principal Investigator
mesh term: Thrombosis
mesh term: Argatroban