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

• ClinicalTrials.gov Identifier: NCT04460651
• Recruitment Status: Completed
• First Posted: July 7, 2020
• Last Update Posted: September 17, 2021
• Sponsor: Estudios Clínicos Latino América
• Collaborator: Amarin Pharma Inc.
• Information provided by (Responsible Party): Estudios Clínicos Latino América

Tracking Information

• First Submitted Date: July 2, 2020
• First Posted Date: July 7, 2020
• Last Update Posted Date: September 17, 2021
• Actual Study Start Date: August 14, 2020
• Actual Primary Completion Date: August 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 20, 2021)

• (A) Prevention Arm: SARS-CoV-2 positivity assesed up to day 60. [ 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).
• (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 ]

Original Primary Outcome Measures (submitted: July 6, 2020)

• Percentage of SARS-CoV-2 positive subjects [ 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).
• Highest mean WHO descriptive score of COVID-19 in the active treatment group compared to the placebo group. [ Time Frame: 60 days ]

Current Secondary Outcome Measures (submitted: September 10, 2021)

• (A) Prevention Arm: High-sensitivity C-reactive Protein (mg/dL) change from baseline to day 60 (key secondary outcome) [ Time Frame: baseline, 60 days ]
  Mean change from baseline will be computed
• (A) Prevention Arm: Triglycerides (mg/dL) change from baseline to day 60 [ Time Frame: baseline, 60 days ]
  Mean change from baseline will be computed
• (A) Prevention Arm: FLU-PRO SCORE change from baseline to day 60 in a subset of subjects [ Time Frame: baseline, 60 days ]
  Mean change from baseline will be computed
• (B) Treatment Arm: COVID 19 related hospitalization or death assessed up to 28 days (key secondary outcome) [ Time Frame: 28 days ]
• (B) Treatment Arm: Alive and out of the hospital at 28 days. [ Time Frame: 28 days ]
• (B) Treatment Arm: In hospital length of stay assessed up to 28 days [ Time Frame: 28 days ]
• (B) Treatment Arm: New requirement of mechanical ventilation assed up to 28 days. [ Time Frame: 28 days ]
• (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 ]
• (B) Treatment Arm: Total mortality assessed up to 28 days [ Time Frame: 28 days ]
• (B) Treatment Arm: FLU-PRO SCORE change from baseline at 28 days [ Time Frame: (B) Treatment Arm: ]

Original Secondary Outcome Measures (submitted: July 6, 2020)

• 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 ]
• 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
• Ultrasensitive C-reactive Protein (mg/dL) at baseline and at day 60 [ Time Frame: baseline, 60 days ]
  Mean change from baseline will be computed
• Difference in hospital length of stay between groups [ Time Frame: 60 days ]
• Difference in duration of mechanical ventilation in both groups [ Time Frame: 60 days ]
• 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 ]
• 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 ]
• Rate of total events, non-fatal myocardial infarction or non-fatal stroke or death (initial and subsequent), up to day 60 [ Time Frame: 60 days ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PREPARE-IT. Prevention and Treatment of COVID19 With EPA in Subjects at Risk - Intervention Trial
• Official Title: PREPARE-IT. Prevention and Treatment of COVID19 With EPA in Subjects at Risk - Intervention Trial
• 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).

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).

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

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

• Condition: COVID19

Intervention

• 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®
• 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)

Study Arms

• Active Comparator: Active treatment
  Participants in this arm will receive study medication icosapent ethyl (IPE) with a specific dose scheme.
  Intervention: Drug: Icosapent ethyl (IPE)
• Placebo Comparator: Placebo
  Participants in this arm will receive Placebo with the same dose scheme as the active comparator:
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 10, 2021): 4093
• Original Estimated Enrollment (submitted: July 6, 2020): 1500
• Actual Study Completion Date: August 30, 2021
• Actual Primary Completion Date: August 30, 2021 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina

Administrative Information

• NCT Number: NCT04460651
• Other Study ID Numbers: PREPARE-IT. Version 4.0
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Estudios Clínicos Latino América
• Study Sponsor: Estudios Clínicos Latino América
• Collaborators: Amarin Pharma Inc.

Investigators

• Principal Investigator: Rafael Diaz, MD; ECLA- Estudios Clínicos Latino América

• PRS Account: Estudios Clínicos Latino América
• Verification Date: August 2021