Amantadine for COVID-19

Summary

Introduction: Corona virus disease 19 (COVID-19) is a devastating pandemic. By early February 2021, more than 102 million people were infected globally with more than 2.2 million reported deaths. Current treatments are approved for hospitalized patients with severe COVID-19 only. No treatment is approved to prevent progression to severe COVID-19 in the early stages of disease. Previous studies have indicated that amantadine is effective against severe acute respiratory syndrome corona virus 1 (SARS-CoV-1). Trials are needed to determine if this translates to a beneficial effect in patients with COVID-19. We hypothesize that preemptive therapy with amantadine of non-hospitalized high-risk adults with SARS-CoV-2 infection disease will prevent disease progression and hospitalization. Methods and analysis: The study is a randomized, double-blinded, placebo-controlled, single center study with two treatment arms; oral amantadine or placebo. Individuals with confirmed SARS-CoV-2 infection and one of following; i) age ≥ 40 years or ii) ≥ 18 years of age with at least one comorbidity or iii) ≥ 18 years of age with a body mass index (BMI) above 30 will be enrolled in the study. We plan to enroll 121 persons in each arm, with a total of 242 participants. Follow up period is 90 days. The primary outcome is disease severity on day 14 assessed by the 8-point COVID outcome scale proposed by the world health organization. Ethics and dissemination: Approvals by the Ethics Committee and National Competent Authorities will be obtained prior to study initiation. Results will be submitted for publication in a peer-reviewed journal and presented at international conferences. Impact: The results of the study will contribute with important knowledge on the efficacy and safety of oral amantadine in the treatment of non-hospitalized high-risk individuals with SARS-CoV-2 infection.

Timeline

Start

2021-06-01

Primary completion

2022-01

Completion

2022-04

Publications

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• Background Nicholson KG, Wiselka MJ. Amantadine for influenza A. BMJ. 1991 Feb 23;302(6774):425-6. doi: 10.1136/bmj.302.6774.425. No abstract available.
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• Background Haase N, Plovsing R, Christensen S, Poulsen LM, Brochner AC, Rasmussen BS, Helleberg M, Jensen JUS, Andersen LPK, Siegel H, Ibsen M, Jorgensen V, Winding R, Iversen S, Pedersen HP, Madsen J, Solling C, Garcia RS, Michelsen J, Mohr T, Mannering A, Espelund US, Bundgaard H, Kirkegaard L, Smitt M, Buck DL, Ribergaard NE, Pedersen HS, Christensen BV, Perner A. Characteristics, interventions, and longer term outcomes of COVID-19 ICU patients in Denmark-A nationwide, observational study. Acta Anaesthesiol Scand. 2021 Jan;65(1):68-75. doi: 10.1111/aas.13701. Epub 2020 Oct 3.
• Background Lendorf ME, Boisen MK, Kristensen PL, Lokkegaard ECL, Krog SM, Brandi L, Brinth LS, Nolsoe RLM, Ryrso C, Eiken P, Bestle MH, Jorgensen IM, Pedersen-Bjergaard U, Lindegaard B, Christensen TB, Fischer TK. Characteristics and early outcomes of patients hospitalised for COVID-19 in North Zealand, Denmark. Dan Med J. 2020 Aug 12;67(9):A06200428.
• Background Gudbjartsson DF, Helgason A, Jonsson H, Magnusson OT, Melsted P, Norddahl GL, Saemundsdottir J, Sigurdsson A, Sulem P, Agustsdottir AB, Eiriksdottir B, Fridriksdottir R, Gardarsdottir EE, Georgsson G, Gretarsdottir OS, Gudmundsson KR, Gunnarsdottir TR, Gylfason A, Holm H, Jensson BO, Jonasdottir A, Jonsson F, Josefsdottir KS, Kristjansson T, Magnusdottir DN, le Roux L, Sigmundsdottir G, Sveinbjornsson G, Sveinsdottir KE, Sveinsdottir M, Thorarensen EA, Thorbjornsson B, Love A, Masson G, Jonsdottir I, Moller AD, Gudnason T, Kristinsson KG, Thorsteinsdottir U, Stefansson K. Spread of SARS-CoV-2 in the Icelandic Population. N Engl J Med. 2020 Jun 11;382(24):2302-2315. doi: 10.1056/NEJMoa2006100. Epub 2020 Apr 14.
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• Background Rodriguez-Morales AJ, Cardona-Ospina JA, Gutierrez-Ocampo E, Villamizar-Pena R, Holguin-Rivera Y, Escalera-Antezana JP, Alvarado-Arnez LE, Bonilla-Aldana DK, Franco-Paredes C, Henao-Martinez AF, Paniz-Mondolfi A, Lagos-Grisales GJ, Ramirez-Vallejo E, Suarez JA, Zambrano LI, Villamil-Gomez WE, Balbin-Ramon GJ, Rabaan AA, Harapan H, Dhama K, Nishiura H, Kataoka H, Ahmad T, Sah R; Latin American Network of Coronavirus Disease 2019-COVID-19 Research (LANCOVID-19). Electronic address: https://www.lancovid.org. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med Infect Dis. 2020 Mar-Apr;34:101623. doi: 10.1016/j.tmaid.2020.101623. Epub 2020 Mar 13.
• Background Sundhedsministeriet. Lov om klage- og erstatningsadgang inden for sundhedsvæsenet 2017

Drugs

Indications