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).
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).
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)
(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
Instituto de Investigaciones Clínicas - Rosario
Rosario, Santa Fe, Argentina
Rafael Diaz, MD, Principal Investigator
ECLA- Estudios Clínicos Latino América