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

Am Heart J. 2021 May:235:54-64. doi: 10.1016/j.ahj.2021.01.018. Epub 2021 Jan 28.

Abstract

Objective: 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).

Background: 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.

Methods: 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.

Conclusion: 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.

Keywords: Atherosclerotic cardiovascular disease; coronavirus disease 2019; icosapent ethyl; seasonal flu; triglycerides; viral upper respiratory infection.

Publication types

  • Clinical Trial Protocol
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atherosclerosis* / complications
  • COVID-19* / complications
  • Cardiovascular Diseases* / complications
  • Cardiovascular Diseases* / prevention & control
  • Eicosapentaenoic Acid* / analogs & derivatives
  • Eicosapentaenoic Acid* / therapeutic use
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Intention to Treat Analysis
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • 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

Substances

  • Eicosapentaenoic Acid
  • eicosapentaenoic acid ethyl ester
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Platelet Aggregation Inhibitors