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

Study Description

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4093 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
• Actual Primary Completion Date: August 30, 2021
• Actual Study Completion Date: August 30, 2021

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. (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).
2. (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 ]

Secondary Outcome Measures :

1. (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
2. (A) Prevention Arm: Triglycerides (mg/dL) change from baseline to day 60 [ Time Frame: baseline, 60 days ]
   Mean change from baseline will be computed
3. (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
4. (B) Treatment Arm: COVID 19 related hospitalization or death assessed up to 28 days (key secondary outcome) [ Time Frame: 28 days ]
5. (B) Treatment Arm: Alive and out of the hospital at 28 days. [ Time Frame: 28 days ]
6. (B) Treatment Arm: In hospital length of stay assessed up to 28 days [ Time Frame: 28 days ]
7. (B) Treatment Arm: New requirement of mechanical ventilation assed up to 28 days. [ Time Frame: 28 days ]
8. (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 ]
9. (B) Treatment Arm: Total mortality assessed up to 28 days [ Time Frame: 28 days ]
10. (B) Treatment Arm: FLU-PRO SCORE change from baseline at 28 days [ Time Frame: (B) Treatment Arm: ]

Eligibility Criteria

• 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

Contacts and Locations

Locations

Argentina

Instituto de Investigaciones Clínicas - Rosario

Rosario, Santa Fe, Argentina, 2000

Sponsors and Collaborators

Estudios Clínicos Latino América

Amarin Pharma Inc.

Investigators

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

More Information

• Responsible Party: Estudios Clínicos Latino América
• ClinicalTrials.gov Identifier: NCT04460651
• Other Study ID Numbers: PREPARE-IT. Version 4.0
• First Posted: July 7, 2020
• Last Update Posted: September 17, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Eicosapentaenoic acid ethyl ester; Platelet Aggregation Inhibitors; Lipid Regulating Agents