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

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

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).

Study Overview

• Status: Terminated
• Conditions: Cardiovascular Diseases; Covid19; Atherosclerosis; Upper Respiratory Tract Infections
• Intervention / Treatment: Drug: Icosapent ethyl

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 39600
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Oakland, California, United States, 94612
      • Division of Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Usual Care
Active Comparator: Intervention	Drug: Icosapent ethyl; 2 g by mouth twice daily for at least 6 months; Other Names: Vascepa

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants who die due to any cause		0-12 months
Percentage of participants experiencing a major adverse cardiovascular event	Death due to any cause, hospitalization for myocardial infarction, or hospitalization for ischemic stroke	0-12 months
Percentage of participants experiencing an expanded major adverse cardiovascular event	Major adverse cardiovascular events, hospitalization for acute coronary syndrome, and coronary revascularization (i.e., percutaneous coronary intervention and/or coronary artery bypass graft)	0-12 months
Percentage of participants who are hospitalized for heart failure		0-12 months
Percentage of participants who are hospitalized for any reason		0-12 months
Percentage of participants who have an emergency department visit for any reason		0-12 months

Collaborators and Investigators

• Sponsor: Kaiser Permanente
• Collaborators: Amarin Corporation
• Investigators: Principal Investigator: Andrew Ambrosy, M.D., Kaiser Permanente; Principal Investigator: Alan S Go, M.D., Kaiser Permanente

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2020
• Primary Completion (Actual): December 15, 2022
• Study Completion (Actual): December 15, 2022

Study Registration Dates

• First Submitted: August 5, 2020
• First Submitted That Met QC Criteria: August 7, 2020
• First Posted (Actual): August 10, 2020

Study Record Updates

• Last Update Posted (Actual): July 18, 2023
• Last Update Submitted That Met QC Criteria: July 14, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Infections; Respiratory Tract Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Cardiovascular Diseases; Atherosclerosis; Respiratory Tract Infections; Platelet Aggregation Inhibitors; Lipid Regulating Agents; Eicosapentaenoic acid ethyl ester
• Other Study ID Numbers: 1597940

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: No