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PREPARE-IT. Prevention and Treatment of COVID19 With EPA in Subjects at Risk - Intervention Trial (PREPARE-IT)

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ClinicalTrials.gov Identifier: NCT04460651
Recruitment Status : Recruiting
First Posted : July 7, 2020
Last Update Posted : May 24, 2021
Sponsor:
Collaborator:
Amarin Pharma Inc.
Information provided by (Responsible Party):
Estudios Clínicos Latino América

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
COVID19 Drug: Icosapent ethyl (IPE) Drug: Placebo Phase 3

Detailed Description:

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 4000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Simple, pragmatic, double-blind, placebo-controlled trial
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: PREPARE-IT. Prevention and Treatment of COVID19 With EPA in Subjects at Risk - Intervention Trial
Actual Study Start Date : August 14, 2020
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Active treatment
Participants in this arm will receive study medication icosapent ethyl (IPE) with a specific dose scheme.
Drug: Icosapent ethyl (IPE)

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)

Other Name: Vascepa®

Placebo Comparator: Placebo
Participants in this arm will receive Placebo with the same dose scheme as the active comparator:
Drug: Placebo
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)




Primary Outcome Measures :
  1. (A) Prevention Arm: Percentage of SARS-CoV-2 positive subjects in the active treatment group compared to the placebo group. [ Time Frame: 60 days ]
    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).

  2. (A) Prevention Arm: Highest mean WHO descriptive score of COVID-19 in hospitalized patients in the active treatment group compared to the placebo group [ Time Frame: 60 days ]
  3. (B) Treatment Arm: Percentage of subjects who required hospitalization or died until day 28 in the active treatment group compared to the placebo group. [ Time Frame: 28 days ]
    Hospitalizations and deaths not related to COVID-19 will not be considered


Secondary Outcome Measures :
  1. (A) Prevention Arm: Highest mean WHO score up to day 60 for the active treatment group as compared to placebo among subjects with a positive test received at any moment during the study after the first visit [ Time Frame: 60 days ]
  2. (A) Prevention Arm: Total cholesterol, LDL, HDL, triglycerides (mg/dL) at baseline and at day 60 [ Time Frame: baseline, 60 days ]
    Mean change from baseline will be computed

  3. (A) Prevention Arm: High-sensitivity C-reactive Protein (mg/dL) at baseline and at day 60 [ Time Frame: baseline, 60 days ]
    Mean change from baseline will be computed

  4. (A) Prevention Arm: Difference in hospital length of stay between groups [ Time Frame: 60 days ]
  5. (A) Prevention Arm: Difference in mechanical ventilation duration between groups [ Time Frame: 60 days ]
  6. (A) Prevention Arm: Rate of hospital admissions due to SARS (Severe Acute Respiratory Syndrome) in patients who were negative for SARS CoV-2 upon admission [ Time Frame: 60 days ]
  7. (A) Prevention Arm: Mean highest WHO descriptive score in active treatment versus placebo groups up to day 60 among hospitalized patients (WHO grades 3 or more) without serum evidence / PCR detecting SARS-CoV-2 infection [ Time Frame: 60 days ]
  8. (A) Prevention Arm: Rate of total events (initial and subsequent): :non-fatal myocardial infarction or non-fatal stroke or death, up to day 60 [ Time Frame: 60 days ]
  9. (B) Treatment Arm: Highest mean WHO score up to day 28 for the active treatment group as compared to placebo [ Time Frame: 28 days ]
  10. (B) Treatment Arm: Difference in hospital length of stay between groups [ Time Frame: 28 days ]
  11. (B) Treatment Arm: Difference in mechanical ventilation incidence between groups [ Time Frame: 28 days ]
  12. (B) Treatment Arm: Rate of total events (initial and subsequent): non-fatal myocardial infarction or non-fatal stroke or death, up to day 28 [ Time Frame: 28 days ]
  13. (B) Treatment Arm: Total mortality in the active treatment group compared to the placebo group. [ Time Frame: 28 days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

(A) Prevention arm:

Inclusion Criteria:

  1. 18 years of age or older and
  2. any subject that is circulating and exposed to the public

Exclusion Criteria:

  1. Previously diagnosed with COVID-19
  2. Positive pregnancy test at the time of study entry in potentially fertile women
  3. Pregnant or breastfeeding women
  4. Subject who has received one or more doses of any vaccine for Sars-Cov-2 or who is scheduled to be vaccinated within the next 60 days
  5. Unable to provide informed consent
  6. Clear contraindication to EPA
  7. Known hypersensitivity to the study drug
  8. Administration of a drug with anticoagulant effects (antiplatelet agents are allowed)
  9. Hemorrhagic Diathesis

(B) Treatment arm:

Inclusion Criteria:

  1. 40 years of age or older and
  2. Covid 19 diagnosis confirmed with SARS Cov-2 test (RT-PCR) and
  3. No more than 7 days from the onset of symptoms and
  4. Without clear indication for hospitalization (1-2 in the WHO COVID-19 Descriptive Score).

Exclusion Criteria:

  1. Hospitalized patient or with a clear indication of hospitalization for COVID-19
  2. Pregnant or breastfeeding women
  3. Lack of access to adequate means of communication via the web
  4. Unable to provide informed consent
  5. Clear contraindication to EPA
  6. Known hypersensitivity to the study drug
  7. Administration of a drug with anticoagulant effects (antiplatelet agents are allowed)
  8. Hemorrhagic Diathesis

Subjects who fill out the pre-selection form will be evaluated and approved for admission to the clinical trial after confirming their entry criteria


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04460651


Contacts
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Contact: Andres Orlandini, MD + 54 341 4450210 aorlandinimd@eclainternational.org
Contact: Rafael Diaz, MD + 54 341 4450210 rdiazmd@eclainternational.org

Locations
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Argentina
Instituto de Investigaciones Clínicas - Rosario Recruiting
Rosario, Santa Fe, Argentina, 2000
Contact: Carolina Chacón, MD       cchacon@gmail.com   
Sponsors and Collaborators
Estudios Clínicos Latino América
Amarin Pharma Inc.
Investigators
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Principal Investigator: Rafael Diaz, MD ECLA- Estudios Clínicos Latino América
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Responsible Party: Estudios Clínicos Latino América
ClinicalTrials.gov Identifier: NCT04460651    
Other Study ID Numbers: PREPARE-IT. Version 3.0
First Posted: July 7, 2020    Key Record Dates
Last Update Posted: May 24, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Estudios Clínicos Latino América:
Icosapent ethyl
Vascepa
Eicosapentaenoic acid ethyl ester
Ethyl-EPA
AMR101
Additional relevant MeSH terms:
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Eicosapentaenoic acid ethyl ester
Platelet Aggregation Inhibitors