Amantadine for COVID-19 treatment (ACT) study: a randomized, double-blinded, placebo-controlled clinical trial
Nina Weis, Signe Bollerup, Jon Dissing Sund, Jakob Borg Glamann, Caroline Vinten, Louise Riger Jensen, Christoffer Sejling, Thomas Nitschke Kledal, Mette Marie Rosenkilde
Clinical Microbiology and Infection, doi:10.1016/j.cmi.2023.06.023
Objectives: The COVID-19 pandemic has revealed a severe need for effective antiviral treatment. The objectives of this study were to assess if pre-emptive treatment with amantadine for COVID-19 in nonhospitalized persons !40 years or adults with comorbidities was able to prevent disease progression and hospitalization. Primary outcomes were clinical status on day 14. Methods: Between 9 June 2021 and 27 January 2022, this randomized, double-blinded, placebocontrolled, single-centre clinical trial included 242 subjects with a follow-up period of 90 days. Subjects were randomly assigned 1:1 to either amantadine 100 mg or placebo twice daily for 5 days. The inclusion criteria were confirmed SARS-CoV-2 infection and at least one of (a) age !40 years, age !18 years and (b) at least one comorbidity, or (c) body mass index !30. The study protocol was published at www. clinicaltrials.gov (unique protocol #02032021) and at www.clinicaltrialregister.eu (EudraCT-number 2021-001177-22). Results: With 121 participants in each arm, we found no difference in the primary endpoint with 82 participants in the amantadine arm, and 92 participants in the placebo arm with no limitations to activities, respectively, and 25 and 37 with limitations to activities in the amantadine arm and the placebo arm, respectively. No participants in either group were admitted to hospital or died. The OR of having state severity increased by 1 in the amantadine group versus placebo was 1.8 (CI 1.0e3.3, [p 0.051]). On day 7, one participant was hospitalized in each group; throughout the study, this increased to five and three participants for amantadine versus placebo treatment (p 0.72). Similarly, on day 7, there was no difference in the status of oropharyngeal swabs. Most participants (108 in each group) were SARS-CoV-2 RNA positive (p 0.84).
Conclusion: We found no effect of amantadine on disease progression of SARS-CoV-2 infection.
Author contributions MMR and TNK conceptualized the idea for this study and obtained the necessary funding. NW administered the clinical project and participated in the investigation of study participants together with SB, JDS, JBG, CV, and LRJ. NW wrote the first draft of the report with input from SB and MMR. CS did the statistical analysis. All authors had full access to all the data in the study, read the manuscript critically, and had final responsibility for the decision to submit for publication. NW, SB, and LRJ have directly accessed and verified the underlying data reported in the manuscript.
Transparency declaration
Conflict of interest NW has been a Clinical Investigator for Abbvie and MSD, and has received unrestricted grants for research from Abbvie and Gilead; all payments made to her institution. TK is the founder, CEO, and a minority shareholder of Synklino A/S. MMR is the founder and a minority shareholder of Synklino A/S. SB, JDS, JBG, CV, LRJ, and CS have no competing interests. The Bio Innovation Institute (BII), Copenhagen, Denmark, supported the study financially and had no role in study design, patient recruitment, in the collection, analysis, or interpretation of data, in the writing of the report, in the decision to submit the paper for publication or any aspect pertaining to the study. None of the Median number of adverse events per person (range) 9 (6e13) 10 (7e15) Median number of serious adverse events per person 0 0 a A total of 108 study..
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