<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/NCT04400799</url>
  </required_header>
  <id_info>
    <org_study_id>OVID Trial</org_study_id>
    <nct_id>NCT04400799</nct_id>
  </id_info>
  <brief_title>Enoxaparin for Primary Thromboprophylaxis in Ambulatory Patients With COVID-19</brief_title>
  <official_title>Enoxaparin for Primary Thromboprophylaxis in Ambulatory Patients With Coronavirus: The Multicenter Randomized Controlled Ovid Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Zurich</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Insel Gruppe AG, University Hospital Bern</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Geneva</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Centre Hospitalier Universitaire Vaudois</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Basel, Switzerland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oncology Institute of Southern Switzerland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Clinica Luganese Moncucco</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Freiburg</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mainz University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Zurich</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The OVID study will show whether prophylactic-dose enoxaparin improves survival and reduces&#xD;
      unplanned hospitalizations in ambulatory patients aged 50 or older diagnosed with COVID-19, a&#xD;
      novel viral disease characterized by severe systemic, pulmonary, and vessel inflammation and&#xD;
      coagulation activation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The following points represent, in summary, the rationale for studying the use of&#xD;
      thromboprophylaxis in ambulatory patients with COVID-19:&#xD;
&#xD;
        1. The risk of thromboembolic events in patients with COVID-19 during anticoagulant&#xD;
           prophylaxis exceeds that observed in medical patients, usually &lt;3%, even in the presence&#xD;
           of seasonal viral infections&#xD;
&#xD;
        2. The cumulative risk of VTE in hospitalized COVID-19 patients is at least 20%, but&#xD;
           possibly higher, as described in several publications&#xD;
&#xD;
        3. The absolute VTE risk in COVID-19 patients requiring intensive care is 69% if screening&#xD;
           strategies are implemented&#xD;
&#xD;
        4. Half of the VTE events, mostly PE, were diagnosed at hospital admission, suggesting that&#xD;
           these events developed during the quarantine period.&#xD;
&#xD;
      Our hypothesis is that early thromboprophylaxis may prevent or limit coagulopathy, and reduce&#xD;
      thromboembolic complications leading to hospitalization or death, in the presence of a mild&#xD;
      COVID disease among outpatients.&#xD;
&#xD;
      The study will be conducted as a multicentre randomized open-label controlled trial. In the&#xD;
      study, a total of 1,000 adult patients aged 50 or older with COVID-19 and candidates to&#xD;
      ambulatory treatment will be randomized to receive enoxaparin 40 mg sc qD or no treatment for&#xD;
      a total of 14 days. The primary outcome will be assessed within 30 days of enrolment.&#xD;
&#xD;
      We implemented two logistical solutions to integrate the process of SARS-CoV2 testing,&#xD;
      pre-screening, screening (hot-line and flyers), in-hospital recruitment, enrolment and&#xD;
      randomization/allocation. A nationwide OVID Hot-Line telephone number will be made available&#xD;
      in 3 languages (German, French, Italian) for interested patients or test centers to contact&#xD;
      the Hot-Line. Standard hygiene precautions will be met at the study centers to avoid&#xD;
      spreading of SARS-CoV2 among other patients or health care workers. Principles of patient and&#xD;
      investigator safety will be applied. Standard procedures concerning privacy, discussion with&#xD;
      patients on details of the study, collection of informed consent, and instruction on how to&#xD;
      administer the study medication will be maintained in conformity with GCP recommendations.&#xD;
      This will also include outcome measurements to be conducted by telephone with standardized&#xD;
      questionnaire.&#xD;
&#xD;
      Enoxaparin (Clexane®) will be given at the recommended dose of 4,000 IU antiXa activity (40&#xD;
      mg/0.4 ml) once daily by SC injection for 14 days.&#xD;
&#xD;
      A single interim analysis is planned at time when the outcomes of 50% of the patients (n=460&#xD;
      plus drop-outs) have been observed (anticipated in February 2022).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    due to results from interim analysis&#xD;
  </why_stopped>
  <start_date type="Actual">June 15, 2020</start_date>
  <completion_date type="Actual">April 12, 2022</completion_date>
  <primary_completion_date type="Actual">February 7, 2022</primary_completion_date>
  <phase>Phase 3</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>hospitalizations</measure>
    <time_frame>30 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>all-cause death</measure>
    <time_frame>30 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of cardiovascular events</measure>
    <time_frame>within 14 days, 30 days, and 90 days of randomization</time_frame>
    <description>including deep vein thrombosis (including catheter-associated), pulmonary embolism, myocardial infarction/myocarditis, arterial ischemia including mesenteric and extremities, acute splanchnic vein thrombosis, or ischemic stroke</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>any hospitalizations</measure>
    <time_frame>within 14 days, 30 days, and 90 days of randomization</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>all-cause death</measure>
    <time_frame>within 14 days, 30 days, and 90 days of randomization</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Net clinical benefit</measure>
    <time_frame>within 14 days, 30 days, and 90 days of enrolment.</time_frame>
    <description>measured by number of cardiovascular events, and major bleeding</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disseminated intravascular coagulation</measure>
    <time_frame>within 14 days, 30 days, and 90 days of enrolment</time_frame>
    <description>ISTH criteria, in-hospital diagnosis</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">475</enrollment>
  <condition>COVID-19</condition>
  <condition>Pulmonary Embolism, Deep Vein Thrombosis</condition>
  <arm_group>
    <arm_group_label>Test Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enoxaparin (Clexane®) will be given at the recommended dose of 4,000 IU antiXa activity (40 mg/0.4 ml) once daily by SC injection for 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No study drug</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enoxaparin 40Mg/0.4Ml Inj Syringe 0.4Ml</intervention_name>
    <description>daily incetion s.c. for 14 days</description>
    <arm_group_label>Test Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients aged 50 years or older with a positive test for SARS-CoV2 in the past 5 days&#xD;
             and eligible for ambulatory treatment.&#xD;
&#xD;
          2. Presence of respiratory symptoms (i.e. cough, sore throat, or shortness of breath) or&#xD;
             body temperature &gt;37.5° C.&#xD;
&#xD;
          3. Ability of the patient to travel to the study center by private transportation,&#xD;
             performed either by accompanying person from same household or by the patient&#xD;
             him/herself&#xD;
&#xD;
          4. Ability to comply with standard hygiene requirements at the time of in-hospital visit,&#xD;
             including a face mask and hand disinfectant.&#xD;
&#xD;
          5. Ability to walk from car to study center or reach it using a wheel chair transport&#xD;
             with the help of an accompanying person from the same household also complying with&#xD;
             standard hygiene requirements.&#xD;
&#xD;
          6. Ability to self-administer prefilled enoxaparin injections after instructions received&#xD;
             at the study center or availability of a person living with the patient to administer&#xD;
             enoxaparin.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any acute or chronic condition posing an indication for anticoagulant treatment, e.g.&#xD;
             atrial fibrillation, prior VTE, acute confirmed symptomatic VTE, acute coronary&#xD;
             syndrome.&#xD;
&#xD;
          2. Anticoagulant thromboprophylaxis deemed necessary in view of the patient's history,&#xD;
             comorbidity or predisposing strong risk factors for thrombosis:&#xD;
&#xD;
               1. Any of the following events occurring in the prior 30 days: fracture of lower&#xD;
                  limb, hospitalization for heart failure, hip/knee replacement, major trauma,&#xD;
                  spinal cord injury, stroke,&#xD;
&#xD;
               2. previous VTE,&#xD;
&#xD;
               3. histologically confirmed malignancy, which was diagnosed or treated (surgery,&#xD;
                  chemotherapy, radiotherapy) in the past 6 months, or recurrent, or metastatic, or&#xD;
                  inoperable.&#xD;
&#xD;
          3. Any clinically relevant bleeding (defined as bleeding requiring hospitalization,&#xD;
             transfusion, surgical intervention, invasive procedures, occurring in a critical&#xD;
             anatomical site, or causing disability) within 30 days prior to randomization or sign&#xD;
             of acute bleeding.&#xD;
&#xD;
          4. Intracerebral bleeding at any time in the past or signs/symptoms consistent with acute&#xD;
             intracranial hemorrhage.&#xD;
&#xD;
          5. Hemoglobin &lt;8 g/dL and platelet count &lt;50 x 109 cells/L confirmed by recent laboratory&#xD;
             test (&lt;90 days).&#xD;
&#xD;
          6. Subjects with any known coagulopathy or bleeding diathesis, including known&#xD;
             significant liver disease associated with coagulopathy.&#xD;
&#xD;
          7. Severe renal insufficiency (baseline creatinine clearance &lt;30 mL/min calculated using&#xD;
             the Cockcroft-Gault formula) confirmed by recent laboratory test (&lt;90 days).&#xD;
&#xD;
          8. Contraindications to enoxaparin therapy, including prior heparin-induced&#xD;
             thrombocytopenia and known hypersensitivity.&#xD;
&#xD;
          9. Current use of dual antiplatelet therapy.&#xD;
&#xD;
         10. Participation in other interventional studies over the past 30 days.&#xD;
&#xD;
         11. Non-compliance or inability to adhere to treatment or lack of a family environment or&#xD;
             support system for home treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nils Kucher, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Zurich</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universitätsklinikum Freiburg</name>
      <address>
        <city>Freiburg</city>
        <zip>79106</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johannes Gutenberg-Universität Mainz</name>
      <address>
        <city>Mainz</city>
        <zip>55122</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Basel</name>
      <address>
        <city>Basel</city>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinic of Hematology, Oncology Institute of Southern Switzerland</name>
      <address>
        <city>Bellinzona</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Bern</name>
      <address>
        <city>Bern</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpitaux Universitaires Genève</name>
      <address>
        <city>Geneva</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Luganese Moncucco</name>
      <address>
        <city>Lugano</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Zurich</name>
      <address>
        <city>Zürich</city>
        <zip>8091</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>May 15, 2020</study_first_submitted>
  <study_first_submitted_qc>May 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <last_update_submitted>May 17, 2022</last_update_submitted>
  <last_update_submitted_qc>May 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Zurich</investigator_affiliation>
    <investigator_full_name>Nils Kucher</investigator_full_name>
    <investigator_title>Prof. Dr. med.</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Pulmonary Embolism</mesh_term>
    <mesh_term>Thrombosis</mesh_term>
    <mesh_term>Embolism</mesh_term>
    <mesh_term>Venous Thrombosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Enoxaparin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04400799
org study id: OVID Trial
nct id: NCT04400799
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The OVID study will show whether prophylactic-dose enoxaparin improves survival and reduces
      unplanned hospitalizations in ambulatory patients aged 50 or older diagnosed with COVID-19, a
      novel viral disease characterized by severe systemic, pulmonary, and vessel inflammation and
      coagulation activation.
The following points represent, in summary, the rationale for studying the use of
      thromboprophylaxis in ambulatory patients with COVID-19:

        1. The risk of thromboembolic events in patients with COVID-19 during anticoagulant
           prophylaxis exceeds that observed in medical patients, usually <3%, even in the presence
           of seasonal viral infections

        2. The cumulative risk of VTE in hospitalized COVID-19 patients is at least 20%, but
           possibly higher, as described in several publications

        3. The absolute VTE risk in COVID-19 patients requiring intensive care is 69% if screening
           strategies are implemented

        4. Half of the VTE events, mostly PE, were diagnosed at hospital admission, suggesting that
           these events developed during the quarantine period.

      Our hypothesis is that early thromboprophylaxis may prevent or limit coagulopathy, and reduce
      thromboembolic complications leading to hospitalization or death, in the presence of a mild
      COVID disease among outpatients.

      The study will be conducted as a multicentre randomized open-label controlled trial. In the
      study, a total of 1,000 adult patients aged 50 or older with COVID-19 and candidates to
      ambulatory treatment will be randomized to receive enoxaparin 40 mg sc qD or no treatment for
      a total of 14 days. The primary outcome will be assessed within 30 days of enrolment.

      We implemented two logistical solutions to integrate the process of SARS-CoV2 testing,
      pre-screening, screening (hot-line and flyers), in-hospital recruitment, enrolment and
      randomization/allocation. A nationwide OVID Hot-Line telephone number will be made available
      in 3 languages (German, French, Italian) for interested patients or test centers to contact
      the Hot-Line. Standard hygiene precautions will be met at the study centers to avoid
      spreading of SARS-CoV2 among other patients or health care workers. Principles of patient and
      investigator safety will be applied. Standard procedures concerning privacy, discussion with
      patients on details of the study, collection of informed consent, and instruction on how to
      administer the study medication will be maintained in conformity with GCP recommendations.
      This will also include outcome measurements to be conducted by telephone with standardized
      questionnaire.

      Enoxaparin (Clexane®) will be given at the recommended dose of 4,000 IU antiXa activity (40
      mg/0.4 ml) once daily by SC injection for 14 days.

      A single interim analysis is planned at time when the outcomes of 50% of the patients (n=460
      plus drop-outs) have been observed (anticipated in February 2022).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: hospitalizations
time frame: 30 days
measure: all-cause death
time frame: 30 days
measure: Number of cardiovascular events
time frame: within 14 days, 30 days, and 90 days of randomization
description: including deep vein thrombosis (including catheter-associated), pulmonary embolism, myocardial infarction/myocarditis, arterial ischemia including mesenteric and extremities, acute splanchnic vein thrombosis, or ischemic stroke
measure: any hospitalizations
time frame: within 14 days, 30 days, and 90 days of randomization
measure: all-cause death
time frame: within 14 days, 30 days, and 90 days of randomization
measure: Net clinical benefit
time frame: within 14 days, 30 days, and 90 days of enrolment.
description: measured by number of cardiovascular events, and major bleeding
measure: Disseminated intravascular coagulation
time frame: within 14 days, 30 days, and 90 days of enrolment
description: ISTH criteria, in-hospital diagnosis
arm group label: Test Group
arm group type: Experimental
description: Enoxaparin (Clexane®) will be given at the recommended dose of 4,000 IU antiXa activity (40 mg/0.4 ml) once daily by SC injection for 14 days.
arm group label: Control Group
arm group type: No Intervention
description: No study drug
intervention type: Drug
intervention name: Enoxaparin 40Mg/0.4Ml Inj Syringe 0.4Ml
description: daily incetion s.c. for 14 days
arm group label: Test Group
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Nils Kucher, Prof.
role: Principal Investigator
affiliation: University of Zurich
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: Switzerland
responsible party type: Principal Investigator
investigator affiliation: University of Zurich
investigator full name: Nils Kucher
investigator title: Prof. Dr. med.
mesh term: COVID-19
mesh term: Pulmonary Embolism
mesh term: Thrombosis
mesh term: Embolism
mesh term: Venous Thrombosis
mesh term: Enoxaparin
sharing ipd: No