Clinical trial NCT04460651: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID19
Keywords: Icosapent ethyl
Vascepa
Eicosapentaenoic acid ethyl ester
Ethyl-EPA
AMR101
Lead sponsor: Estudios Clínicos Latino América
Sponsor class: OTHER
Collaborators: name: Amarin Pharma Inc.
First posted: 2020-07-07
Enrollment: 4093
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Simple, pragmatic, double-blind, placebo-controlled trial
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: (A) Prevention Arm: SARS-CoV-2 positivity assesed up to day 60.
timeFrame: 60 days
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
timeFrame: 28 days
Secondary outcomes:
measure: (A) Prevention Arm: High-sensitivity C-reactive Protein (mg/dL) change from baseline to day 60 (key secondary outcome)
timeFrame: baseline, 60 days
measure: (A) Prevention Arm: Triglycerides (mg/dL) change from baseline to day 60
timeFrame: baseline, 60 days
measure: (A) Prevention Arm: FLU-PRO SCORE change from baseline to day 60 in a subset of subjects
timeFrame: baseline, 60 days
measure: (B) Treatment Arm: COVID 19 related hospitalization or death assessed up to 28 days (key secondary outcome)
timeFrame: 28 days
measure: (B) Treatment Arm: Alive and out of the hospital at 28 days.
timeFrame: 28 days
measure: (B) Treatment Arm: In hospital length of stay assessed up to 28 days
timeFrame: 28 days
measure: (B) Treatment Arm: New requirement of mechanical ventilation assed up to 28 days.
timeFrame: 28 days
measure: (B) Treatment Arm: Total events: non-fatal myocardial infarction or non-fatal stroke or death (initial and subsequent), until day 28.
timeFrame: 28 days
measure: (B) Treatment Arm: Total mortality assessed up to 28 days
timeFrame: 28 days
measure: (B) Treatment Arm: FLU-PRO SCORE change from baseline at 28 days
timeFrame: (B) Treatment Arm:
Other outcomes:
Locations:
city: Rosario
country: Argentina
facility: Instituto de Investigaciones Clínicas - Rosario
state: Santa Fe
Study officials:
affiliation: ECLA- Estudios Clínicos Latino América
name: Rafael Diaz, MD
role: PRINCIPAL_INVESTIGATOR
References: