Itraconazole for COVID-19: preclinical studies and a proof-of-concept randomized clinical trial

Laurens Liesenborghs, Isabel Spriet, Dirk Jochmans, Ann Belmans, Iwein Gyselinck, Laure-Anne Teuwen, Sebastiaan ter Horst, Erwin Dreesen, Tatjana Geukens, Matthias M. Engelen, Ewout Landeloos, Vincent Geldhof, Helga Ceunen, Barbara Debaveye, Bert Vandenberk, Lorenz van der Linden, Sofie Jacobs, Lana Langendries, Robbert Boudewijns, Thuc Nguyen Dan DoWinston Chiu, Xinyu Wang, Xin Zhang, Birgit Weynand, Thomas Vanassche, Timothy Devos, Geert Meyfroidt, Wim Janssens, Robin Vos, Pieter Vermeersch, Joost Wauters, Geert Verbeke, Paul De Munter, Suzanne J. F. Kaptein, Joana Rocha-Pereira, Leen Delang, Eric Van Wijngaerden, Johan Neyts, Peter Verhamme

Research output: Contribution to journalA1: Web of Science-articlepeer-review

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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.

FUNDING: KU Leuven, Research Foundation - Flanders (FWO), Horizon 2020, Bill and Melinda Gates Foundation.

Original languageEnglish
Article number103288
Number of pages11
Publication statusPublished - 2021


  • Animals
  • Antiviral Agents/administration & dosage
  • COVID-19/drug therapy
  • Chlorocebus aethiops
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Female
  • Humans
  • Itraconazole/administration & dosage
  • Male
  • Mesocricetus
  • Middle Aged
  • Pneumonia, Viral/drug therapy
  • Proof of Concept Study
  • SARS-CoV-2/drug effects
  • Treatment Outcome
  • Vero Cells


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