Rationale and design of the pragmatic randomized trial of icosapent ethyl for high cardiovascular risk adults (MITIGATE)

• Published in: The American heart journal 2021-05, Vol.235, p.54-64
• Main Authors: Ambrosy, Andrew P., Malik, Umar I., Thomas, Rachel C., Parikh, Rishi V., Tan, Thida C., Goh, Choon H., Selby, Van N., Solomon, Matthew D., Avula, Harshith R., Fitzpatrick, Jesse K., Skarbinski, Jacek, Philip, Sephy, Granowitz, Craig, Bhatt, Deepak L., Go, Alan S.
• Format: Article
• Language: English
• Subjects: Adults; Aged; Anti-inflammatory agents; Antiviral activity; Arteriosclerosis; Atherosclerosis; Atherosclerosis - complications; Atherosclerotic cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - complications; Cardiovascular Diseases - prevention & control; Complications; coronavirus disease 2019; Coronaviruses; COVID-19; COVID-19 - complications; Drug dosages; Eicosapentaenoic Acid - analogs & derivatives; Eicosapentaenoic Acid - therapeutic use; Electronic health records; Electronic medical records; Fatty acids; Female; Health care; Health risks; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; icosapent ethyl; Inflammation; Influenza; Intention to Treat Analysis; Male; Meals; Middle Aged; Morbidity; Mortality; Multicenter Studies as Topic; Omega-3 fatty acids; Platelet Aggregation Inhibitors - therapeutic use; Pragmatic Clinical Trials as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Respiratory Tract Infections - complications; Respiratory Tract Infections - virology; Risk management; seasonal flu; Trial Designs; Triglycerides; Viral diseases; viral upper respiratory infection
• ISSN: 0002-8703; 1097-6744; 1097-6744
• DOI: 10.1016/j.ahj.2021.01.018

The MITIGATE study aims to evaluate the real-world clinical effectiveness of pre-treatment with icosapent ethyl (IPE), compared with usual care, on laboratory-confirmed viral upper respiratory infection (URI)-related morbidity and mortality in adults with established atherosclerotic cardiovascular disease (ASCVD). IPE is a highly purified and stable omega-3 fatty acid prescription medication that is approved for cardiovascular risk reduction in high-risk adults on statin therapy with elevated triglycerides. Preclinical data and clinical observations suggest that IPE may have pleiotropic effects including antiviral and anti-inflammatory properties that may prevent or reduce the downstream sequelae and cardiopulmonary consequences of viral URIs. MITIGATE is a virtual, electronic health record-based, open-label, randomized, pragmatic clinical trial enrolling ∼16,500 participants within Kaiser Permanente Northern California – a fully integrated and learning health care delivery system with 21 hospitals and >255 ambulatory clinics serving ∼4.5 million members. Adults ≥50 years with established ASCVD and no prior history of coronavirus disease 2019 (COVID-19) will be prospectively identified and pre-randomized in a 1:10 allocation ratio (∼ 1,500 IPE: ∼15,000 usual care) stratified by age and previous respiratory health status to the intervention (IPE 2 grams by mouth twice daily with meals) vs the control group (usual care) for a minimum follow-up duration of 6 months. The co-primary endpoints are moderate-to-severe laboratory-confirmed viral URI and worst clinical status due to a viral URI at any point in time. The MITIGATE study will inform clinical practice by providing evidence on the real-world clinical effectiveness of pretreatment with IPE to prevent and/or reduce the sequelae of laboratory-confirmed viral URIs in a high-risk cohort of patients with established ASCVD.