<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/NCT04435015</url>
  </required_header>
  <id_info>
    <org_study_id>2000028279</org_study_id>
    <nct_id>NCT04435015</nct_id>
  </id_info>
  <brief_title>The Utility of Camostat Mesylate in Patients With COVID-19 Associated Coagulopathy (CAC) and Cardiovascular Complications</brief_title>
  <official_title>The Utility of Camostat Mesylate in Patients With COVID-19 Associated Coagulopathy (CAC) and Cardiovascular Complications</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ono Pharmaceutical Co. Ltd</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Yale University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary aim of this study is to determine whether Camostat mesylate reduces SARS-COV-2&#xD;
      associated coagulopathy. Additional aims are to determine the effect of Camostat mesylate on&#xD;
      SARS-COV-2 associated myocardial injury, to assess duration of hypoxia or intubation, to&#xD;
      evaluate the length of intensive care unit and hospital stay, and assess mortality rates.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The trial is in-patient only. Participants are identified by the hospital physicians and&#xD;
      house staff, and contacted by research study personnel. Potential participants fulfilling&#xD;
      inclusion criteria and not fulfilling exclusion criteria who agree to participate and sign&#xD;
      the informed consent undergo the enrollment process. Ono Pharmaceutical, Japan, will provide&#xD;
      Camostat mesylate tablets. The Yale New Haven Hospital research pharmacy will receive and&#xD;
      store the drug within 15-25C range according to protocol storage requirements.&#xD;
&#xD;
      Microcrystalline Cellulose NF (PH-102) for placebo formulation will be acquired from Fagron.&#xD;
      Empty gelatin capsules Size 0, for over-encapsulation will be acquired from Fagron. Before&#xD;
      Ono Pharmaceutical can send the drug, an IND will be obtained from the FDA.&#xD;
&#xD;
      Principal Investigator and the Yale New Haven Hospital research pharmacy will keep&#xD;
      accountability records for all investigational products acquired, dispensed, used and&#xD;
      disposed. Drugs are administered by nurses. There will be no restriction on taking other&#xD;
      medications, activities or food intake. There are two arms to the study: (a)&#xD;
      pharmacy-formulated placebo 3 times a day (b) 200 mg Camostat mesylate to be taken three&#xD;
      times daily. Each arm will have 100 subjects. All patients will receive treatment until&#xD;
      discharged. Participants will be randomized equally to Camostat mesylate or identical&#xD;
      appearing placebo using a permuted-block design with variable block size. The actual&#xD;
      treatment assignment will be concealed from the investigators and the participants. The&#xD;
      randomization scheme will be generated by the statistical group.&#xD;
&#xD;
      Participants have the option of refusing study drug. If the participant decides to stop the&#xD;
      drug or blood drawing he or she would be dropped from the trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No funding&#xD;
  </why_stopped>
  <start_date type="Anticipated">November 2021</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</primary_completion_date>
  <phase>Phase 1/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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent change in plasma D-Dimer</measure>
    <time_frame>7 days</time_frame>
    <description>The sum percent change in D-Dimer over 7 days will be compared to day 1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Safety and adverse event</measure>
    <time_frame>3 months</time_frame>
    <description>The first assessment on mortality and complications will be carried out 3 months after the start of the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in plasma Fibrinogen levels</measure>
    <time_frame>7 days</time_frame>
    <description>Percent change in fibrinogen over 7 days compared to day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in plasma troponin</measure>
    <time_frame>7 days</time_frame>
    <description>Percent change in troponin over 7 days compared to day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>New onset cardiomyopathy</measure>
    <time_frame>7 days</time_frame>
    <description>New onset cardiomyopathy defined by a reduction of EF by greater than 10% or less than 45% will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of intubation</measure>
    <time_frame>7 days</time_frame>
    <description>Days with hypoxia (Room Air O2 Sat&lt;93%) or days intubated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of stay in the intensive care unit</measure>
    <time_frame>28 days</time_frame>
    <description>The number of days in the intensive care unit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to discharge from hospital</measure>
    <time_frame>30 days</time_frame>
    <description>The number of days since admission to discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of major adverse cardiovascular events</measure>
    <time_frame>7 days</time_frame>
    <description>The ocurrence of major adverse cardiovascular events (MACE): MI, stroke, CHF, PCI, death from cardiovascular disease will be studied.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Coagulopathy</condition>
  <condition>Cardiovascular Complication</condition>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Camostat mesylate 200 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be given Camostat mesylate three times daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Microcrystalline Cellulose</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will be given placebo three times daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Camostat Mesylate</intervention_name>
    <description>Participants will be given Camostat mesylate three times daily.</description>
    <arm_group_label>Camostat mesylate 200 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Microcrystalline Cellulose, NF</intervention_name>
    <description>Participants will be given Microcrystalline Cellulose (placebo) three times daily.</description>
    <arm_group_label>Microcrystalline Cellulose</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. . Positive COVID-19 test result.&#xD;
&#xD;
          2. Diagnosis of COVID-19 associated coagulopathy and cardiac complications based on&#xD;
             D-Dimer, fibrinogen, TnT, CTPE, ischemic EKG changes&#xD;
&#xD;
          3. Provision of informed consent. In patients with altered mental status consents can be&#xD;
             obtained from the power of attorney.&#xD;
&#xD;
          4. Stated willingness to comply with all study procedures and availability for the&#xD;
             duration of the study&#xD;
&#xD;
          5. Male or female, age 18 or older&#xD;
&#xD;
          6. Diagnosed with hypoxia requiring intubation or positive air pressure.&#xD;
&#xD;
          7. Diagnose with DVT/PE by ultrasound and CTPE and/or&#xD;
&#xD;
          8. Elevated D-Dimer and/or&#xD;
&#xD;
          9. Greater than 2-fold increase in TnT&#xD;
&#xD;
         10. Ischemic EKG changes with ST depression or elevation more than 1 mm in 2 consecutive&#xD;
             leads&#xD;
&#xD;
         11. Ability to administer oral medication.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. GFR&lt;30 mL/min&#xD;
&#xD;
          2. Severe bleeding requiring blood transfusion of drop of 5% in HCT.&#xD;
&#xD;
          3. Pregnancy or lactation&#xD;
&#xD;
          4. Known allergic reactions to components of Camostat mesylate.&#xD;
&#xD;
          5. Subjects under age 18&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Arya Mani, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>May 11, 2022</last_update_submitted>
  <last_update_submitted_qc>May 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Yale University</investigator_affiliation>
    <investigator_full_name>Arya Mani</investigator_full_name>
    <investigator_title>Professor of Medicine and of Genetics</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>Hemostatic Disorders</mesh_term>
    <mesh_term>Blood Coagulation Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Camostat</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Study protocol and clinical study report will be shared 1 year after completion of the study</ipd_time_frame>
  </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/NCT04435015
org study id: 2000028279
nct id: NCT04435015
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The primary aim of this study is to determine whether Camostat mesylate reduces SARS-COV-2
      associated coagulopathy. Additional aims are to determine the effect of Camostat mesylate on
      SARS-COV-2 associated myocardial injury, to assess duration of hypoxia or intubation, to
      evaluate the length of intensive care unit and hospital stay, and assess mortality rates.
The trial is in-patient only. Participants are identified by the hospital physicians and
      house staff, and contacted by research study personnel. Potential participants fulfilling
      inclusion criteria and not fulfilling exclusion criteria who agree to participate and sign
      the informed consent undergo the enrollment process. Ono Pharmaceutical, Japan, will provide
      Camostat mesylate tablets. The Yale New Haven Hospital research pharmacy will receive and
      store the drug within 15-25C range according to protocol storage requirements.

      Microcrystalline Cellulose NF (PH-102) for placebo formulation will be acquired from Fagron.
      Empty gelatin capsules Size 0, for over-encapsulation will be acquired from Fagron. Before
      Ono Pharmaceutical can send the drug, an IND will be obtained from the FDA.

      Principal Investigator and the Yale New Haven Hospital research pharmacy will keep
      accountability records for all investigational products acquired, dispensed, used and
      disposed. Drugs are administered by nurses. There will be no restriction on taking other
      medications, activities or food intake. There are two arms to the study: (a)
      pharmacy-formulated placebo 3 times a day (b) 200 mg Camostat mesylate to be taken three
      times daily. Each arm will have 100 subjects. All patients will receive treatment until
      discharged. Participants will be randomized equally to Camostat mesylate or identical
      appearing placebo using a permuted-block design with variable block size. The actual
      treatment assignment will be concealed from the investigators and the participants. The
      randomization scheme will be generated by the statistical group.

      Participants have the option of refusing study drug. If the participant decides to stop the
      drug or blood drawing he or she would be dropped from the trial.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percent change in plasma D-Dimer
time frame: 7 days
description: The sum percent change in D-Dimer over 7 days will be compared to day 1
measure: Overall Safety and adverse event
time frame: 3 months
description: The first assessment on mortality and complications will be carried out 3 months after the start of the study.
measure: Change in plasma Fibrinogen levels
time frame: 7 days
description: Percent change in fibrinogen over 7 days compared to day 1
measure: Change in plasma troponin
time frame: 7 days
description: Percent change in troponin over 7 days compared to day 1
measure: New onset cardiomyopathy
time frame: 7 days
description: New onset cardiomyopathy defined by a reduction of EF by greater than 10% or less than 45% will be measured
measure: Duration of intubation
time frame: 7 days
description: Days with hypoxia (Room Air O2 Sat<93%) or days intubated
measure: Length of stay in the intensive care unit
time frame: 28 days
description: The number of days in the intensive care unit
measure: Time to discharge from hospital
time frame: 30 days
description: The number of days since admission to discharge
measure: Occurrence of major adverse cardiovascular events
time frame: 7 days
description: The ocurrence of major adverse cardiovascular events (MACE): MI, stroke, CHF, PCI, death from cardiovascular disease will be studied.
arm group label: Camostat mesylate 200 mg
arm group type: Experimental
description: Participants will be given Camostat mesylate three times daily.
arm group label: Microcrystalline Cellulose
arm group type: Placebo Comparator
description: Participants will be given placebo three times daily.
intervention type: Drug
intervention name: Camostat Mesylate
description: Participants will be given Camostat mesylate three times daily.
arm group label: Camostat mesylate 200 mg
intervention type: Drug
intervention name: Microcrystalline Cellulose, NF
description: Participants will be given Microcrystalline Cellulose (placebo) three times daily.
arm group label: Microcrystalline Cellulose
other name: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Arya Mani, MD
role: Principal Investigator
affiliation: Yale University
responsible party type: Principal Investigator
investigator affiliation: Yale University
investigator full name: Arya Mani
investigator title: Professor of Medicine and of Genetics
mesh term: COVID-19
mesh term: Hemostatic Disorders
mesh term: Blood Coagulation Disorders
mesh term: Camostat
sharing ipd: Yes
ipd info type: Study Protocol
ipd info type: Clinical Study Report (CSR)
ipd time frame: Study protocol and clinical study report will be shared 1 year after completion of the study