A Pragmatic Randomized Trial of Icosapent Ethyl for High-Cardiovascular Risk Adults

Study Overview
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Brief Summary
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MITIGATE is a prospective, open-label, parallel-group, randomized, pragmatic clinical trial. The MITIGATE Study has been designed to evaluate the real-world clinical effectiveness of pre-treatment with icosapent ethyl (IPE), also known as Vascepa®, compared to usual standard of care to prevent and reduce the sequelae of laboratory-confirmed viral upper respiratory infection (URI)-related (i.e., COVID-19, influenza, and other known viral respiratory pathogens) morbidity and mortality in a high-risk cohort of adults with established atherosclerotic cardiovascular disease (ASCVD).

Detailed Description
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For the MITIGATE study, eligible members receiving care within Kaiser Permanente Northern California (KPNC) will be identified and screened electronically in a 1:10 intervention to control allocation (i.e., IPE vs. usual care) stratified by age and pre-existing respiratory status. Patients randomly assigned and enrolled into the intervention arm will be asked to take IPE (2 grams by mouth twice daily) for a minimum of 6 months and until study completion. Patients assigned to the control arm (i.e., usual care) will be passively followed only electronically via the electronic health record (EHR).

Official Title
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A Pragmatic Randomized Trial of Icosapent Ethyl for High-Cardiovascular Risk Adults (MITIGATE)

Conditions
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Covid19, Atherosclerosis, Cardiovascular Diseases, Upper Respiratory Tract Infections

Intervention / Treatment
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* Drug: Icosapent ethyl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide informed consent (for the intervention arm only) No prior history of confirmed COVID-19 (i.e., based on a positive FDA-approved assay for SARS-CoV-2 and no documented FDA-approved serological test results for antibodies to SARS-CoV-2 found in health system databases) Established ASCVD (i.e., defined as prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass surgery, ischemic stroke, and/or peripheral artery disease) At least 12 months of continuous health plan membership and prescription drug benefit prior to enrollment A registered e-mail address with the health care delivery system in order to facilitate obtaining electronic consent for study participation Exclusion Criteria: Receipt of IPE on or within 12 months before the day of enrollment Known hypersensitivity to IPE, fish, and/or shellfish Documented use of any omega-3 fatty acid medications or dietary supplements containing omega-3 fatty acids in the EHR Women who are pregnant or planning to become pregnant Hospitalization for myocardial infarction and/or elective percutaneous coronary intervention within the past 1 month Currently receiving triple anti-thrombotic therapy Stage D heart failure Severe liver disease End-stage renal disease requiring chronic dialysis or estimated glomerular filtration rate <15 mL/min/1.73 m2 Metastatic cancer and/or receiving active systemic chemotherapy Institutionalized and/or receiving palliative care

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pragmatic randomized clinical trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention<br> | Drug: Icosapent ethyl<br>* 2 g by mouth twice daily for at least 6 months<br>* Other names: Vascepa;|
| No Intervention: Usual Care<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of confirmed viral URIs | Confirmed viral URIs (i.e., including recurrent events) (i.e., COVID-19, influenza, and other known viral respiratory pathogens) based on laboratory testing (i.e., FDA or locally-approved testing modalities) | 0-12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with moderate or severe confirmed viral URIs | Confirmed viral URIs (i.e., including recurrent events) (i.e., COVID-19, influenza, and other known viral respiratory pathogens) based on laboratory testing (i.e., FDA or locally-approved testing modalities) with an oxygen saturation <94% on room air and/or requiring any form of supplemental oxygen. | 0-12 months | 
| Worst clinical status due to a confirmed viral URI | At any point in time based on a 7-point ordinal scale (i.e., 1 = death, 2 = mechanically ventilated/extracorporeal membrane oxygenation, 3 = high flow supplemental oxygen, 4 = low flow supplemental oxygen, 5 = hospitalized with no supplemental oxygen requirements, 6 = urgent care or emergency department visit not leading to hospitalization, and 7 = no relevant clinical encounters) | 0-12 months |