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Published February 1, 2022 | Version v1
Journal article Open

High-dose ivermectin for early treatment of COVID-19 (COVER study): a randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial

  • 1. Department of Infectious Tropical Diseases and Microbiology, IRCCS Sacro Cuore-Don Calabria Hospital, Negrar di Valpolicella, Verona, Italy
  • 2. Dipartimento ad attività integrata medico-generale, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy
  • 3. Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri-IRCCS, Milan, Italy
  • 4. Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri-IRCCS, Milan, Italy
  • 5. Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri-IRCCS, Milan, Italy
  • 6. Dipartimento di Scienze Biomediche e Cliniche 'Luigi Sacco', Università degli Studi di Milano, Milan, Italy
  • 7. Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri-IRCCS, Milan, Italy
  • 8. Infectious Disease Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
  • 9. Clinical Analysis Laboratory and Transfusional Medicine, IRCCS Sacro Cuore-Don Calabria Hospital, Negrar di Valpolicella, Verona, Italy
  • 10. Hospital Pharmacy, IRCCS Sacro Cuore-Don Calabria hospital, Negrar di Valpolicella, Verona, Italy
  • 11. Department of Infectious Tropical Diseases and Microbiology, IRCCS Sacro Cuore-Don Calabria Hospital, Negrar di Valpolicella, Verona, Italy; Department of Diagnostics and Public Health, University of Verona, Verona, Italy

Description

High concentrations of ivermectin demonstrated antiviral activity against SARS-CoV-2 in vitro. The aim of this study was to assess the safety and efficacy of high-dose ivermectin in reducing viral load in individuals with early SARS-CoV-2 infection. This was a randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial. Participants were adults recently diagnosed with asymptomatic/oligosymptomatic SARS-CoV-2 infection. Exclusion criteria were: pregnant or lactating women; CNS disease; dialysis; severe medical condition with prognosis <6 months; warfarin treatment; and antiviral/chloroquine phosphate/hydroxychloroquine treatment. Participants were assigned (ratio 1:1:1) according to a randomised permuted block procedure to one of the following arms: placebo (arm A); single-dose ivermectin 600 μg/kg plus placebo for 5 days (arm B); and single-dose ivermectin 1200 μg/kg for 5 days (arm C). Primary outcomes were serious adverse drug reactions (SADRs) and change in viral load at Day 7. From 31 July 2020 to 26 May 2021, 32 participants were randomised to arm A, 29 to arm B and 32 to arm C. Recruitment was stopped on 10 June because of a dramatic drop in cases. The safety analysis included 89 participants and the change in viral load was calculated in 87 participants. No SADRs were registered. Mean (S.D.) log10 viral load reduction was 2.9 (1.6) in arm C, 2.5 (2.2) in arm B and 2.0 (2.1) in arm A, with no significant differences (P = 0.099 and 0.122 for C vs. A and B vs. A, respectively). High-dose ivermectin was safe but did not show efficacy to reduce viral load.

For anonymization purpose, the dates of recruitment have been shifted of an unspecified number of days. However, timeframe between follow up visits remains fixed.

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COVER _ REDCap_CODEBOOK.pdf

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