<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/NCT04460651</url>
  </required_header>
  <id_info>
    <org_study_id>PREPARE-IT. Version 4.0</org_study_id>
    <nct_id>NCT04460651</nct_id>
  </id_info>
  <brief_title>PREPARE-IT. Prevention and Treatment of COVID19 With EPA in Subjects at Risk - Intervention Trial</brief_title>
  <acronym>PREPARE-IT</acronym>
  <official_title>PREPARE-IT. Prevention and Treatment of COVID19 With EPA in Subjects at Risk - Intervention Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Estudios Clínicos Latino América</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Amarin Pharma Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Estudios Clínicos Latino América</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The PREPARE-IT investigator-initiated trial program is a simple, pragmatic, therapeutic&#xD;
      strategy evaluating pure icosapent ethyl (IPE) at initially higher doses intended to reduce&#xD;
      infection rates and subsequent morbidity and mortality among subjects at high risk of&#xD;
      infection due to COVID-19 (prevention arm), and to reduce the hospitalization rate and&#xD;
      complications in patients with a positive diagnosis of COVID-19 (treatment arm).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Few vaccines have received emergency authorization providing relative immunity, reducing both&#xD;
      transmission and infection rates and subsequent associated morbidity and mortality. However,&#xD;
      broad access to vaccines is limited globally, and emergence of COVID-19 viral mutations and&#xD;
      vaccine breakthrough cases underscore the need for complementary effective therapies.&#xD;
&#xD;
      To date, there are limited systemic options available for effective treatment from&#xD;
      viral-inhibitors, polyclonal antibodies (immunomodulatory drugs) to mitigate the inflammatory&#xD;
      cascade and subsequent cytokine storm, and low-dose steroids such as dexamethasone in&#xD;
      high-risk patients, which was associated with a reduction in mortality.&#xD;
&#xD;
      Icosapent ethyl (IPE) is a safe, well-tolerated oral therapy proven to be effective in&#xD;
      improving outcomes in patients with established cardiovascular disease or diabetes with one&#xD;
      or more additional risk factors.&#xD;
&#xD;
      In the context of COVID-19, a recent pilot study on 50 patients on a loading dose of 8g/day&#xD;
      for three days, followed by 4g/daily showed a significant improvement in validated&#xD;
      patient-reported FLU-PRO score symptoms. A corresponding reduction in a key biomarker of&#xD;
      inflammation (hs-CRP) was also detected within the IPE arm at 14 days.&#xD;
&#xD;
      While this pilot study provides the first evidence of an early anti-inflammatory effect of&#xD;
      IPE, to confirm these findings, we designed a randomized, placebo-controlled study program&#xD;
      investigating IPE with a similar loading dose intended to reduce infection rates and&#xD;
      subsequent morbidity and mortality among subjects at high risk of infection from SARS-CoV-2&#xD;
      (prevention arm), and to reduce the hospitalization rate and complications in patients with a&#xD;
      positive diagnosis of COVID-19 (treatment arm).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 14, 2020</start_date>
  <completion_date type="Actual">August 30, 2021</completion_date>
  <primary_completion_date type="Actual">August 30, 2021</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>
    <intervention_model_description>Simple, pragmatic, double-blind, placebo-controlled trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>(A) Prevention Arm: SARS-CoV-2 positivity assesed up to day 60.</measure>
    <time_frame>60 days</time_frame>
    <description>SARS-CoV-2 positive subjects are defined as subjects with positive tests for SARS-CoV-2 RT-PCR or for SARS-CoV-2 lgG antibodies after developing COVID-19 disease at any stage within the follow-up period (including those subjects with or without symptomatic COVID-19 evaluated before the final visit) or those individuals who test positive for SARS-CoV-2 RT-PCR or for SARS-CoV-2 lgG antibodies at the final visit (day 60).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>(B) Treatment Arm: COVID 19 related hospitalization (indication for hospitalization per the blinded investigator or actual hospitalization) or death assessed up to 28 days</measure>
    <time_frame>28 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>(A) Prevention Arm: High-sensitivity C-reactive Protein (mg/dL) change from baseline to day 60 (key secondary outcome)</measure>
    <time_frame>baseline, 60 days</time_frame>
    <description>Mean change from baseline will be computed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(A) Prevention Arm: Triglycerides (mg/dL) change from baseline to day 60</measure>
    <time_frame>baseline, 60 days</time_frame>
    <description>Mean change from baseline will be computed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(A) Prevention Arm: FLU-PRO SCORE change from baseline to day 60 in a subset of subjects</measure>
    <time_frame>baseline, 60 days</time_frame>
    <description>Mean change from baseline will be computed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(B) Treatment Arm: COVID 19 related hospitalization or death assessed up to 28 days (key secondary outcome)</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(B) Treatment Arm: Alive and out of the hospital at 28 days.</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(B) Treatment Arm: In hospital length of stay assessed up to 28 days</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(B) Treatment Arm: New requirement of mechanical ventilation assed up to 28 days.</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(B) Treatment Arm: Total events: non-fatal myocardial infarction or non-fatal stroke or death (initial and subsequent), until day 28.</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(B) Treatment Arm: Total mortality assessed up to 28 days</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(B) Treatment Arm: FLU-PRO SCORE change from baseline at 28 days</measure>
    <time_frame>(B) Treatment Arm:</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">4093</enrollment>
  <condition>COVID19</condition>
  <arm_group>
    <arm_group_label>Active treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in this arm will receive study medication icosapent ethyl (IPE) with a specific dose scheme.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants in this arm will receive Placebo with the same dose scheme as the active comparator:</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Icosapent ethyl (IPE)</intervention_name>
    <description>Participants in this arm will receive study medication IPE with the following dosage schedule:&#xD;
8 g of IPE (4 capsules every 12 hours - morning and evening, with food) for the first three days followed by 4 g of IPE (2 capsules every 12 hours - morning and evening, with food) thereafter (days 4-28 for treatment arm and 4-60 for prevention arm)</description>
    <arm_group_label>Active treatment</arm_group_label>
    <other_name>Vascepa®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants in this arm will receive placebo with the following dosage schedule: 8 g of placebo (4 capsules every 12 hours - morning and evening, with food) for the first three days followed by 4 g of placebo (2 capsules every 12 hours - morning and evening, with food) thereafter (days 4-28 for treatment arm and 4-60 for prevention arm)</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        (A) Prevention arm:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. 18 years of age or older and&#xD;
&#xD;
          2. any subject that is circulating and exposed to the public&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previously diagnosed with COVID-19&#xD;
&#xD;
          2. Positive pregnancy test at the time of study entry in potentially fertile women&#xD;
&#xD;
          3. Pregnant or breastfeeding women&#xD;
&#xD;
          4. Subject who has received one or more doses of any vaccine for Sars-Cov-2 or who is&#xD;
             scheduled to be vaccinated within the next 60 days&#xD;
&#xD;
          5. Unable to provide informed consent&#xD;
&#xD;
          6. Clear contraindication to EPA&#xD;
&#xD;
          7. Known hypersensitivity to the study drug&#xD;
&#xD;
          8. Administration of a drug with anticoagulant effects (antiplatelet agents are allowed)&#xD;
&#xD;
          9. Hemorrhagic Diathesis&#xD;
&#xD;
        (B) Treatment arm:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. 40 years of age or older and&#xD;
&#xD;
          2. Covid 19 diagnosis confirmed with SARS Cov-2 test (RT-PCR) and&#xD;
&#xD;
          3. No more than 7 days from the onset of symptoms and&#xD;
&#xD;
          4. Without clear indication for hospitalization (1-2 in the WHO COVID-19 Descriptive&#xD;
             Score).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hospitalized patient or with a clear indication of hospitalization for COVID-19&#xD;
&#xD;
          2. Pregnant or breastfeeding women&#xD;
&#xD;
          3. Lack of access to adequate means of communication via the web&#xD;
&#xD;
          4. Unable to provide informed consent&#xD;
&#xD;
          5. Clear contraindication to EPA&#xD;
&#xD;
          6. Known hypersensitivity to the study drug&#xD;
&#xD;
          7. Administration of a drug with anticoagulant effects (antiplatelet agents are allowed)&#xD;
&#xD;
          8. Hemorrhagic Diathesis&#xD;
&#xD;
        Subjects who fill out the pre-selection form will be evaluated and approved for admission&#xD;
        to the clinical trial after confirming their entry criteria&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rafael Diaz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>ECLA- Estudios Clínicos Latino América</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Instituto de Investigaciones Clínicas - Rosario</name>
      <address>
        <city>Rosario</city>
        <state>Santa Fe</state>
        <zip>2000</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>July 2, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>September 10, 2021</last_update_submitted>
  <last_update_submitted_qc>September 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 17, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Icosapent ethyl</keyword>
  <keyword>Vascepa</keyword>
  <keyword>Eicosapentaenoic acid ethyl ester</keyword>
  <keyword>Ethyl-EPA</keyword>
  <keyword>AMR101</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>Eicosapentaenoic acid ethyl ester</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/NCT04460651
org study id: PREPARE-IT. Version 4.0
nct id: NCT04460651
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The PREPARE-IT investigator-initiated trial program is a simple, pragmatic, therapeutic
      strategy evaluating pure icosapent ethyl (IPE) at initially higher doses intended to reduce
      infection rates and subsequent morbidity and mortality among subjects at high risk of
      infection due to COVID-19 (prevention arm), and to reduce the hospitalization rate and
      complications in patients with a positive diagnosis of COVID-19 (treatment arm).
Few vaccines have received emergency authorization providing relative immunity, reducing both
      transmission and infection rates and subsequent associated morbidity and mortality. However,
      broad access to vaccines is limited globally, and emergence of COVID-19 viral mutations and
      vaccine breakthrough cases underscore the need for complementary effective therapies.

      To date, there are limited systemic options available for effective treatment from
      viral-inhibitors, polyclonal antibodies (immunomodulatory drugs) to mitigate the inflammatory
      cascade and subsequent cytokine storm, and low-dose steroids such as dexamethasone in
      high-risk patients, which was associated with a reduction in mortality.

      Icosapent ethyl (IPE) is a safe, well-tolerated oral therapy proven to be effective in
      improving outcomes in patients with established cardiovascular disease or diabetes with one
      or more additional risk factors.

      In the context of COVID-19, a recent pilot study on 50 patients on a loading dose of 8g/day
      for three days, followed by 4g/daily showed a significant improvement in validated
      patient-reported FLU-PRO score symptoms. A corresponding reduction in a key biomarker of
      inflammation (hs-CRP) was also detected within the IPE arm at 14 days.

      While this pilot study provides the first evidence of an early anti-inflammatory effect of
      IPE, to confirm these findings, we designed a randomized, placebo-controlled study program
      investigating IPE with a similar loading dose intended to reduce infection rates and
      subsequent morbidity and mortality among subjects at high risk of infection from SARS-CoV-2
      (prevention arm), and to reduce the hospitalization rate and complications in patients with a
      positive diagnosis of COVID-19 (treatment arm).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Simple, pragmatic, double-blind, placebo-controlled trial
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: (A) Prevention Arm: SARS-CoV-2 positivity assesed up to day 60.
time frame: 60 days
description: SARS-CoV-2 positive subjects are defined as subjects with positive tests for SARS-CoV-2 RT-PCR or for SARS-CoV-2 lgG antibodies after developing COVID-19 disease at any stage within the follow-up period (including those subjects with or without symptomatic COVID-19 evaluated before the final visit) or those individuals who test positive for SARS-CoV-2 RT-PCR or for SARS-CoV-2 lgG antibodies at the final visit (day 60).
measure: (B) Treatment Arm: COVID 19 related hospitalization (indication for hospitalization per the blinded investigator or actual hospitalization) or death assessed up to 28 days
time frame: 28 days
measure: (A) Prevention Arm: High-sensitivity C-reactive Protein (mg/dL) change from baseline to day 60 (key secondary outcome)
time frame: baseline, 60 days
description: Mean change from baseline will be computed
measure: (A) Prevention Arm: Triglycerides (mg/dL) change from baseline to day 60
time frame: baseline, 60 days
description: Mean change from baseline will be computed
measure: (A) Prevention Arm: FLU-PRO SCORE change from baseline to day 60 in a subset of subjects
time frame: baseline, 60 days
description: Mean change from baseline will be computed
measure: (B) Treatment Arm: COVID 19 related hospitalization or death assessed up to 28 days (key secondary outcome)
time frame: 28 days
measure: (B) Treatment Arm: Alive and out of the hospital at 28 days.
time frame: 28 days
measure: (B) Treatment Arm: In hospital length of stay assessed up to 28 days
time frame: 28 days
measure: (B) Treatment Arm: New requirement of mechanical ventilation assed up to 28 days.
time frame: 28 days
measure: (B) Treatment Arm: Total events: non-fatal myocardial infarction or non-fatal stroke or death (initial and subsequent), until day 28.
time frame: 28 days
measure: (B) Treatment Arm: Total mortality assessed up to 28 days
time frame: 28 days
measure: (B) Treatment Arm: FLU-PRO SCORE change from baseline at 28 days
time frame: (B) Treatment Arm:
arm group label: Active treatment
arm group type: Active Comparator
description: Participants in this arm will receive study medication icosapent ethyl (IPE) with a specific dose scheme.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants in this arm will receive Placebo with the same dose scheme as the active comparator:
intervention type: Drug
intervention name: Icosapent ethyl (IPE)
description: Participants in this arm will receive study medication IPE with the following dosage schedule:
8 g of IPE (4 capsules every 12 hours - morning and evening, with food) for the first three days followed by 4 g of IPE (2 capsules every 12 hours - morning and evening, with food) thereafter (days 4-28 for treatment arm and 4-60 for prevention arm)
arm group label: Active treatment
other name: Vascepa®
intervention type: Drug
intervention name: Placebo
description: Participants in this arm will receive placebo with the following dosage schedule: 8 g of placebo (4 capsules every 12 hours - morning and evening, with food) for the first three days followed by 4 g of placebo (2 capsules every 12 hours - morning and evening, with food) thereafter (days 4-28 for treatment arm and 4-60 for prevention arm)
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Rafael Diaz, MD
role: Principal Investigator
affiliation: ECLA- Estudios Clínicos Latino América
facility: 
country: Argentina
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Eicosapentaenoic acid ethyl ester
sharing ipd: No