Please use this identifier to cite or link to this item:
http://hdl.handle.net/1942/35835
Title: | Itraconazole for COVID-19: preclinical studies and a proof-of-concept randomized clinical trial | Authors: | Liesenborghs , L Spriet, I Jochmans, D Belmans , A Gyselinck, I Teuwen, LA ter Horst, S Dreesen , E Geukens , T Engelen, MM Landeloos, E Geldhof, V Ceunen, H Debaveye, B Vandenberk , B van der Linden , L Jacobs, S Langendries , L Boudewijns, R Do, TND Chiu, W Wang , XY Zhang, X Weynand, B Vanassche, T Devos , T Meyfroidt, G Janssens , W Vos, R Vermeersch, P Wauters, J VERBEKE, Geert De Munter , P Kaptein, SJF Rocha-Pereira, J Delang , L Van Wijngaerden, E Neyts, J Verhamme, P |
Issue Date: | 2021 | Publisher: | ELSEVIER | Source: | EBioMedicine (Amsterdam), 66 (Art N° 103288) | Abstract: | Background: The antifungal drug itraconazole exerts in vitro activity against SARS-CoV-2 in Vero and human Caco-2 cells. Preclinical and clinical studies are required to investigate if itraconazole is effective for the treatment and/or prevention of COVID-19.Methods: Due to the initial absence of preclinical models, the effect of itraconazole was explored in a clinical, proof-of-concept, open-label, single-center study, in which hospitalized COVID-19 patients were randomly assigned to standard of care with or without itraconazole. Primary outcome was the cumulative score of the clinical status until day 15 based on the 7-point ordinal scale of the World Health Organization. In parallel, itraconazole was evaluated in a newly established hamster model of acute SARS-CoV-2 infection and transmission, as soon as the model was validated.Findings: In the hamster acute infection model, itraconazole did not reduce viral load in lungs, stools or ileum, despite adequate plasma and lung drug concentrations. In the transmission model, itraconazole failed to prevent viral transmission. The clinical trial was prematurely discontinued after evaluation of the preclinical studies and because an interim analysis showed no signal for a more favorable outcome with itraconazole: mean cumulative score of the clinical status 49 vs 47, ratio of geometric means 1.01 (95% CI 0.85 to 1.19) for itraconazole vs standard of care.Interpretation: Despite in vitro activity, itraconazole was not effective in a preclinical COVID-19 hamster model. This prompted the premature termination of the proof-of-concept clinical study. (C) 2021 The Authors. Published by Elsevier B.V. | Keywords: | COVID-19;SARS-CoV-2;itraconazole;drug repurposing;antivirals | Document URI: | http://hdl.handle.net/1942/35835 | ISSN: | 2352-3964 | e-ISSN: | 2352-3964 | DOI: | 10.1016/j.ebiom.2021.103288 | ISI #: | 000647447600003 | Rights: | 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2022 |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Itraconazole for COVID-19_ preclinical studies and a proof-of-concept randomized clinical trial.pdf | Published version | 2.56 MB | Adobe PDF | View/Open |
WEB OF SCIENCETM
Citations
18
checked on Oct 6, 2024
Page view(s)
24
checked on Sep 7, 2022
Download(s)
74
checked on Sep 7, 2022
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.