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

NCT ID: NCT04460651

Last Updated: 2021-09-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 4093 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-14
• Study Completion Date: 2021-08-30

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).

Conditions

COVID19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Active treatment

Participants in this arm will receive study medication icosapent ethyl (IPE) with a specific dose scheme.

Group Type: ACTIVE_COMPARATOR

Icosapent ethyl (IPE)

Intervention Type: DRUG

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)

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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)

Interventions

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)

Intervention Type: 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)

Intervention Type: DRUG

Other Intervention Names

Vascepa®

Eligibility Criteria

Inclusion Criteria

1. 18 years of age or older and

2. any subject that is circulating and exposed to the public

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. 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:

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Amarin Pharma Inc.

INDUSTRY

Sponsor Role: collaborator

Estudios Clínicos Latino América

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rafael Diaz, MD

Role: PRINCIPAL_INVESTIGATOR

ECLA- Estudios Clínicos Latino América

Locations

Instituto de Investigaciones Clínicas - Rosario

Rosario, Santa Fe Province, Argentina

Countries

Argentina

Other Identifiers

PREPARE-IT. Version 4.0

Identifier Type: -

Identifier Source: org_study_id