<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/NCT04445935</url>
  </required_header>
  <id_info>
    <org_study_id>MRC-05-082</org_study_id>
    <nct_id>NCT04445935</nct_id>
  </id_info>
  <brief_title>Anticoagulation in Patients Suffering From COVID-19 Disease The ANTI-CO Trial</brief_title>
  <official_title>Anticoagulation in Patients Suffering From COVID-19 Disease-The Anti-Co Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hamad Medical Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hamad Medical Corporation</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with COVID-19 associated ARDS and mechanical ventilation have a high mortality. Part&#xD;
      of the disease is an activation of the coagulation system which seems to contribute to&#xD;
      clotformation in the pulmonary bloodstream. Recently we implemented an algorithm applying&#xD;
      higher doses of heparins (LMWH). However, this approach could not inhibit clotformation&#xD;
      enough. Bivalirudin could prevent clotformation better and support dissolving existing clots.&#xD;
&#xD;
      Therefore, we want to compare 50 patients with the standard treatment with 50 patients under&#xD;
      bivalirudin treatment which we normally apply in patients with a HIT-syndrome.&#xD;
&#xD;
      Our primary outcome measure is oxygenation reflected as P/F ratio.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The pandemic of COVID-19, a newly upcoming viral disease caused by SARS-CoV-2, puts the whole&#xD;
      worlds health system under pressure.&#xD;
&#xD;
      Patients suffering from this disease mainly develop respiratory symptoms, which can lead to&#xD;
      severe acute respiratory distress syndrome (ARDS) necessitating ICU admission in 10-20% of&#xD;
      the cases admitted to hospital. In addition to these symptoms, patients show lymphopenia,&#xD;
      cardiac symptoms and altered coagulation profiles. Although those patients are treated in the&#xD;
      ICU the mortality there is more than 20% due to multiorgan failure.&#xD;
&#xD;
      One of the recent insights in this disease is its effect on the coagulation system. Meanwhile&#xD;
      we know that the coagulation system gets activated. Furthermore, it seems that clot formation&#xD;
      takes place in the pulmonary micro-vasculature which could contribute to the widely observed&#xD;
      gas-exchange impairment. Therefore, many centers apply empiric anticoagulation for their&#xD;
      COVID-patients. At the moment, we at HMC, also apply an empirical anticoagulation protocol as&#xD;
      our standard approach. However, this is a symptomatic treatment without good proof.&#xD;
&#xD;
      Bivalirudin is a well-known agent which is used in HMC for cases in which anticoagulation is&#xD;
      needed, but a contraindication for heparin exists (i.e. HIT syndrome). This drug has an&#xD;
      interesting pharmacologic profile. It acts independent of antithrombin (AT), the&#xD;
      physiological compound which enhances heparin effects under normal circumstances. This lack&#xD;
      of dependence on AT, makes Bivalirudin an attractive choice in light of the contradictory&#xD;
      reports on the levels of AT during COVID infection. If AT levels are decreased during the&#xD;
      infection, heparin (as well as LMWH) cannot work efficiently, which would render our&#xD;
      treatment less effective. Luckily, bivalirudin acts without the support of AT, so we could&#xD;
      bypass this problem. In addition, bivalirudin has some fibrinolytic activities. It inhibits&#xD;
      clot-bound thrombin which as a result destabilizes the clot rendering it more susceptible to&#xD;
      thrombolysis. This property partially supports the dissolving of clots and could support&#xD;
      re-opening the pulmonary microcirculation.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      To prove the positive effect of anticoagulation with bivalirudin intravenously on&#xD;
      gas-exchange in patients with COVID-19 and respiratory failure on invasive mechanical&#xD;
      ventilation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">June 28, 2020</start_date>
  <completion_date type="Anticipated">March 28, 2021</completion_date>
  <primary_completion_date type="Anticipated">September 28, 2020</primary_completion_date>
  <phase>Phase 4</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>
    <intervention_model_description>This is a randomized controlled trial.</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>This study will be blinded to the above mentioned group. The PI is not involved in active treatment. Patients are sedated and ventilated when treatment starts and finally the outcome assessors will not be knowing the patients treatment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>P/F ratio</measure>
    <time_frame>three days of intervention</time_frame>
    <description>the P/F ratio is a surrogate parameter for oxygenation in ARDS.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Kidney function</measure>
    <time_frame>three days of intervention</time_frame>
    <description>The kidney function frequently is deteriorated in COVID-19 patients</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Anticoagulation in COVID-19 ARDS</condition>
  <arm_group>
    <arm_group_label>Standard treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In this arm the patients will be treated according to our standard anticoagulation protocol.&#xD;
The patients will not be treated with Bivalirudin (the investigational drug).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Bivalirudin arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The patients will be anticoagulated according to the institutional HIT-protocol which uses Bivalirudin as anticoagulant.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bivalirudin Injection</intervention_name>
    <description>The patients will receive iv Bivalirudin according to the institutional HIT protocol.</description>
    <arm_group_label>Bivalirudin arm</arm_group_label>
    <other_name>anticoagulation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard treatment</intervention_name>
    <description>This group will receive standard anticoagulation with LMWH/UFH</description>
    <arm_group_label>Standard treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patient (≥ 18 years of age)&#xD;
&#xD;
          -  Positive COVID-test&#xD;
&#xD;
          -  Under mechanical ventilation&#xD;
&#xD;
          -  D-Dimers&gt;1.2 mg/L&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Allergy to the drug (bivalirudin)&#xD;
&#xD;
          -  Inherited coagulation abnormalities&#xD;
&#xD;
          -  No informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marcus Lance, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>HMC</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Marcus Lance, MD, PhD</last_name>
    <phone>00974</phone>
    <phone_ext>33530292</phone_ext>
    <email>mlance@hamad.qa</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Stefan Roehrig, MD, MBA</last_name>
    <phone>00974</phone>
    <phone_ext>66030924</phone_ext>
    <email>srohrig@hamad.qa</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hamad Medical Corporation</name>
      <address>
        <city>Doha</city>
        <country>Qatar</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nadir Kharma, MD</last_name>
      <phone>00974</phone>
      <phone_ext>55118621</phone_ext>
      <email>nkharma@hamad.qa</email>
    </contact>
  </location>
  <location_countries>
    <country>Qatar</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 24, 2020</study_first_posted>
  <last_update_submitted>June 23, 2020</last_update_submitted>
  <last_update_submitted_qc>June 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hamad Medical Corporation</investigator_affiliation>
    <investigator_full_name>Dr. Marcus Daniel Lance</investigator_full_name>
    <investigator_title>Professor Dr. Marcus Lance</investigator_title>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>ARDS</keyword>
  <keyword>Anticoagulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bivalirudin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>this will depend on IRB advice</ipd_description>
  </patient_data>
  <!-- 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/NCT04445935
org study id: MRC-05-082
nct id: NCT04445935
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Patients with COVID-19 associated ARDS and mechanical ventilation have a high mortality. Part
      of the disease is an activation of the coagulation system which seems to contribute to
      clotformation in the pulmonary bloodstream. Recently we implemented an algorithm applying
      higher doses of heparins (LMWH). However, this approach could not inhibit clotformation
      enough. Bivalirudin could prevent clotformation better and support dissolving existing clots.

      Therefore, we want to compare 50 patients with the standard treatment with 50 patients under
      bivalirudin treatment which we normally apply in patients with a HIT-syndrome.

      Our primary outcome measure is oxygenation reflected as P/F ratio.
The pandemic of COVID-19, a newly upcoming viral disease caused by SARS-CoV-2, puts the whole
      worlds health system under pressure.

      Patients suffering from this disease mainly develop respiratory symptoms, which can lead to
      severe acute respiratory distress syndrome (ARDS) necessitating ICU admission in 10-20% of
      the cases admitted to hospital. In addition to these symptoms, patients show lymphopenia,
      cardiac symptoms and altered coagulation profiles. Although those patients are treated in the
      ICU the mortality there is more than 20% due to multiorgan failure.

      One of the recent insights in this disease is its effect on the coagulation system. Meanwhile
      we know that the coagulation system gets activated. Furthermore, it seems that clot formation
      takes place in the pulmonary micro-vasculature which could contribute to the widely observed
      gas-exchange impairment. Therefore, many centers apply empiric anticoagulation for their
      COVID-patients. At the moment, we at HMC, also apply an empirical anticoagulation protocol as
      our standard approach. However, this is a symptomatic treatment without good proof.

      Bivalirudin is a well-known agent which is used in HMC for cases in which anticoagulation is
      needed, but a contraindication for heparin exists (i.e. HIT syndrome). This drug has an
      interesting pharmacologic profile. It acts independent of antithrombin (AT), the
      physiological compound which enhances heparin effects under normal circumstances. This lack
      of dependence on AT, makes Bivalirudin an attractive choice in light of the contradictory
      reports on the levels of AT during COVID infection. If AT levels are decreased during the
      infection, heparin (as well as LMWH) cannot work efficiently, which would render our
      treatment less effective. Luckily, bivalirudin acts without the support of AT, so we could
      bypass this problem. In addition, bivalirudin has some fibrinolytic activities. It inhibits
      clot-bound thrombin which as a result destabilizes the clot rendering it more susceptible to
      thrombolysis. This property partially supports the dissolving of clots and could support
      re-opening the pulmonary microcirculation.

      Objectives:

      To prove the positive effect of anticoagulation with bivalirudin intravenously on
      gas-exchange in patients with COVID-19 and respiratory failure on invasive mechanical
      ventilation.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a randomized controlled trial.
primary purpose: Supportive Care
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: This study will be blinded to the above mentioned group. The PI is not involved in active treatment. Patients are sedated and ventilated when treatment starts and finally the outcome assessors will not be knowing the patients treatment.
measure: P/F ratio
time frame: three days of intervention
description: the P/F ratio is a surrogate parameter for oxygenation in ARDS.
measure: Kidney function
time frame: three days of intervention
description: The kidney function frequently is deteriorated in COVID-19 patients
arm group label: Standard treatment
arm group type: Active Comparator
description: In this arm the patients will be treated according to our standard anticoagulation protocol.
The patients will not be treated with Bivalirudin (the investigational drug).
arm group label: Bivalirudin arm
arm group type: Experimental
description: The patients will be anticoagulated according to the institutional HIT-protocol which uses Bivalirudin as anticoagulant.
intervention type: Drug
intervention name: Bivalirudin Injection
description: The patients will receive iv Bivalirudin according to the institutional HIT protocol.
arm group label: Bivalirudin arm
other name: anticoagulation
intervention type: Drug
intervention name: Standard treatment
description: This group will receive standard anticoagulation with LMWH/UFH
arm group label: Standard treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Marcus Lance, MD, PhD
role: Principal Investigator
affiliation: HMC
last name: Marcus Lance, MD, PhD
phone: 00974
phone ext: 33530292
email: mlance@hamad.qa
last name: Stefan Roehrig, MD, MBA
phone: 00974
phone ext: 66030924
email: srohrig@hamad.qa
facility: 
status: Recruiting
contact: 
country: Qatar
responsible party type: Principal Investigator
investigator affiliation: Hamad Medical Corporation
investigator full name: Dr. Marcus Daniel Lance
investigator title: Professor Dr. Marcus Lance
mesh term: COVID-19
mesh term: Bivalirudin
sharing ipd: Undecided
ipd description: this will depend on IRB advice