A randomized trial of icosapent ethyl in ambulatory patients with COVID-19

Andrew Kosmopoulos; Deepak L Bhatt; Gus Meglis; Raj Verma; Yi Pan; Adrian Quan; Hwee Teoh; Maya Verma; Lixia Jiao; Robert Wang; Rebecca A Juliano; Mahesh Kajil; Mikhail N Kosiborod; Basel Bari; Abdullahi A Berih; Mallory Aguilar; Antonnette Escano; Andrew Leung; Idelta Coelho; Makoto Hibino; Rafael Díaz; R Preston Mason; Ph Gabriel Steg; Tabassome Simon; Alan S Go; Andrew P Ambrosy; Richard Choi; Arthur M Kushner; Lawrence A Leiter; Mohammed Al-Omran; Subodh Verma; C David Mazer

doi:10.1016/j.isci.2021.103040

A randomized trial of icosapent ethyl in ambulatory patients with COVID-19

iScience. 2021 Sep 24;24(9):103040. doi: 10.1016/j.isci.2021.103040. Epub 2021 Aug 26.

Authors

Andrew Kosmopoulos^{1

2

3}, Deepak L Bhatt⁴, Gus Meglis¹, Raj Verma¹, Yi Pan², Adrian Quan², Hwee Teoh^{2

5}, Maya Verma¹, Lixia Jiao⁶, Robert Wang⁶, Rebecca A Juliano⁶, Mahesh Kajil¹, Mikhail N Kosiborod^{7

8

9

10}, Basel Bari¹¹, Abdullahi A Berih¹², Mallory Aguilar¹, Antonnette Escano¹, Andrew Leung¹³, Idelta Coelho¹³, Makoto Hibino², Rafael Díaz¹⁴, R Preston Mason¹⁵, Ph Gabriel Steg^{16

17

18}, Tabassome Simon^{17

19}, Alan S Go^{20

21

22}, Andrew P Ambrosy^{20

23}, Richard Choi²⁴, Arthur M Kushner²⁵, Lawrence A Leiter^{5

26

27}, Mohammed Al-Omran^{28

29}, Subodh Verma^{1

2

3

29

30}, C David Mazer^{31

32

33}

Affiliations

¹ North York Diagnostic and Cardiac Centre, Toronto, ON, Canada.
² Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
³ Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada.
⁴ Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA.
⁵ Division of Endocrinology and Metabolism, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
⁶ Amarin Pharma Inc., Bridgewater, NJ, USA.
⁷ Department of Cardiology, Saint Luke's Mid America Heart Institute, Kansas City, MO, USA.
⁸ Department of Medicine, University of Missouri-Kansas City, Missouri, USA.
⁹ The George Institute for Global Health, Sydney, NSW, Australia.
¹⁰ University of New South Wales, Sydney, NSW, Australia.
¹¹ Markham Health+Plex Medical Centre, Markham, ON, Canada.
¹² Humber Centre for Family Health, Etobicoke, ON, Canada.
¹³ Alpha Laboratories Inc., Toronto, ON, Canada.
¹⁴ Estudios Clínicos Latino América, Instituto Cardiovascular de Rosario, Rosario, Argentina.
¹⁵ Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁶ Université de Paris, Assistance Publique-Hôpitaux de Paris, INSERM 1148, Paris, France.
¹⁷ French Alliance for Cardiovascular Trials (FACT), Paris, France.
¹⁸ National Heart & Lung Institute NHLI, Imperial College, Royal Brompton Hospital, London, UK.
¹⁹ Department of Clinical Pharmacology, Unité de Recherche Clinique (URCEST), Assistance Publique-Hôpitaux de Paris, Hôpital Saint Antoine, Sorbonne Université, site St Antoine, INSERM U-698, Paris, France.
²⁰ Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
²¹ Departments of Epidemiology, Biostatistics and Medicine, University of California at San Francisco, San Francisco, CA, USA.
²² Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
²³ Division of Cardiology, Kaiser Permanente San Francisco Medical Center, San Francisco, CA, USA.
²⁴ Riverside Cardiology and Diagnostic Imaging; Division of Cardiology, St. Joseph's Health Centre, Unity Health Toronto, Toronto, ON, Canada.
²⁵ Humber River Hospital, Toronto, ON, Canada.
²⁶ Department of Medicine, University of Toronto, Toronto, ON, Canada.
²⁷ Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.
²⁸ Division of Vascular Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
²⁹ Department of Surgery, University of Toronto, Toronto, ON, Canada.
³⁰ Canadian Medical and Surgical Knowledge Translation Research Group, Toronto, ON, Canada.
³¹ Department of Anesthesia, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
³² Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada.
³³ Department of Physiology, University of Toronto, Toronto, ON, Canada.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic remains a source of considerable morbidity and mortality throughout the world. Therapeutic options to reduce symptoms, inflammatory response, or disease progression are limited. This randomized open-label trial enrolled 100 ambulatory patients with symptomatic COVID-19 in Toronto, Canada. Results indicate that icosapent ethyl (8 g daily for 3 days followed by 4 g daily for 11 days) significantly reduced high-sensitivity C-reactive protein (hs-CRP) and improved symptomatology compared with patients assigned to usual care. Specifically, the primary biomarker endpoint, change in hs-CRP, was significantly reduced by 25% among treated patients (-0.5 mg/L, interquartile range [IQR] [-6.9,0.4], within-group p = 0.011). Conversely, a non-significant 5.6% reduction was observed among usual care patients (-0.1 mg/L, IQR [-3.2,1.7], within-group p = 0.51). An unadjusted between-group primary biomarker analysis was non-significant (p = 0.082). Overall, this report provides evidence of an early anti-inflammatory effect of icosapent ethyl in a modest sample, including an initial well-tolerated loading dose, in symptomatic outpatients with COVID-19. ClinicalTrials.gov Identifier: NCT04412018.

Keywords: Health sciences; Medicine.

Associated data

ClinicalTrials.gov/NCT04412018

Grants and funding

K23 HL150159/HL/NHLBI NIH HHS/United States