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Hydroxychloroquine as Prophylaxis for COVID-19: A Review

The impact of the COVID-19 pandemic worldwide has led to a desperate search for effective drugs and vaccines. There are still no approved agents for disease prophylaxis. We thus decided to use a drug repositioning strategy to perform a state-of-the-art review of a promising but controversial drug, h...

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Autores principales: Monti, Manuela, Vertogen, Bernadette, Masini, Carla, Donati, Caterina, Lilli, Claudia, Zingaretti, Chiara, Musuraca, Gerardo, De Giorgi, Ugo, Cerchione, Claudio, Farolfi, Alberto, Cortesi, Pietro, Viale, Pierluigi, Martinelli, Giovanni, Nanni, Oriana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744418/
https://www.ncbi.nlm.nih.gov/pubmed/33343376
http://dx.doi.org/10.3389/fphar.2020.605185
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author Monti, Manuela
Vertogen, Bernadette
Masini, Carla
Donati, Caterina
Lilli, Claudia
Zingaretti, Chiara
Musuraca, Gerardo
De Giorgi, Ugo
Cerchione, Claudio
Farolfi, Alberto
Cortesi, Pietro
Viale, Pierluigi
Martinelli, Giovanni
Nanni, Oriana
author_facet Monti, Manuela
Vertogen, Bernadette
Masini, Carla
Donati, Caterina
Lilli, Claudia
Zingaretti, Chiara
Musuraca, Gerardo
De Giorgi, Ugo
Cerchione, Claudio
Farolfi, Alberto
Cortesi, Pietro
Viale, Pierluigi
Martinelli, Giovanni
Nanni, Oriana
author_sort Monti, Manuela
collection PubMed
description The impact of the COVID-19 pandemic worldwide has led to a desperate search for effective drugs and vaccines. There are still no approved agents for disease prophylaxis. We thus decided to use a drug repositioning strategy to perform a state-of-the-art review of a promising but controversial drug, hydroxychloroquine (HCQ), in an effort to provide an objective, scientific and methodologically correct overview of its potential prophylactic role. The advantage of using known drugs is that their toxicity profile is well known and there are fewer commercial interests (e.g., expired patents), thus allowing the scientific community to be freer of constraints. The main disadvantage is that the economic resources are almost always insufficient to promote large multinational clinical trials. In the present study, we reviewed the literature and available data on the prophylactic use of HCQ. We also took an in-depth look at all the published clinical data on the drug and examined ongoing clinical trials (CTs) from the most important CT repositories to identify a supporting rationale for HCQ prophylactic use. Our search revealed a substantial amount of preclinical data but a lack of clinical data, highlighting the need to further assess the translational impact of in vitro data in a clinical setting. We identified 77 CTs using a multiplicity of HCQ schedules, which clearly indicates that we are still far from reaching a standard of care. The majority of the CTs (92%) are randomized and 53% are being conducted in a phase 3 or 2/3 setting. The comparator is placebo or control in 55 (77%) of the randomized studies. Forty-eight (62%) CTs expect to enroll up to 1,000 subjects and 50 (71%) plan to recruit healthcare workers (HCW). With regard to drug schedules, 45 (58.5%) CTs have planned a loading dose, while 18 (23.4%) have not; the loading dose is 800 mg in 19 trials (42.2%), 400 mg in 19 (42.2%), 600 mg in 4 (8.9%) and 1,200 mg in 1 (2.2%). Forty trials include at least one daily schedule, while 19 have at least one weekly schedule. Forty-one (53.2%) will have a treatment duration of more than 30 days. Awaiting further developments that can only derive from the results of these prospective randomized CTs, the take-home message of our review is that a correct methodological approach is the key to understanding whether prophylactic HCQ can really represent an effective strategy in preventing COVID-19.
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spelling pubmed-77444182020-12-18 Hydroxychloroquine as Prophylaxis for COVID-19: A Review Monti, Manuela Vertogen, Bernadette Masini, Carla Donati, Caterina Lilli, Claudia Zingaretti, Chiara Musuraca, Gerardo De Giorgi, Ugo Cerchione, Claudio Farolfi, Alberto Cortesi, Pietro Viale, Pierluigi Martinelli, Giovanni Nanni, Oriana Front Pharmacol Pharmacology The impact of the COVID-19 pandemic worldwide has led to a desperate search for effective drugs and vaccines. There are still no approved agents for disease prophylaxis. We thus decided to use a drug repositioning strategy to perform a state-of-the-art review of a promising but controversial drug, hydroxychloroquine (HCQ), in an effort to provide an objective, scientific and methodologically correct overview of its potential prophylactic role. The advantage of using known drugs is that their toxicity profile is well known and there are fewer commercial interests (e.g., expired patents), thus allowing the scientific community to be freer of constraints. The main disadvantage is that the economic resources are almost always insufficient to promote large multinational clinical trials. In the present study, we reviewed the literature and available data on the prophylactic use of HCQ. We also took an in-depth look at all the published clinical data on the drug and examined ongoing clinical trials (CTs) from the most important CT repositories to identify a supporting rationale for HCQ prophylactic use. Our search revealed a substantial amount of preclinical data but a lack of clinical data, highlighting the need to further assess the translational impact of in vitro data in a clinical setting. We identified 77 CTs using a multiplicity of HCQ schedules, which clearly indicates that we are still far from reaching a standard of care. The majority of the CTs (92%) are randomized and 53% are being conducted in a phase 3 or 2/3 setting. The comparator is placebo or control in 55 (77%) of the randomized studies. Forty-eight (62%) CTs expect to enroll up to 1,000 subjects and 50 (71%) plan to recruit healthcare workers (HCW). With regard to drug schedules, 45 (58.5%) CTs have planned a loading dose, while 18 (23.4%) have not; the loading dose is 800 mg in 19 trials (42.2%), 400 mg in 19 (42.2%), 600 mg in 4 (8.9%) and 1,200 mg in 1 (2.2%). Forty trials include at least one daily schedule, while 19 have at least one weekly schedule. Forty-one (53.2%) will have a treatment duration of more than 30 days. Awaiting further developments that can only derive from the results of these prospective randomized CTs, the take-home message of our review is that a correct methodological approach is the key to understanding whether prophylactic HCQ can really represent an effective strategy in preventing COVID-19. Frontiers Media S.A. 2020-12-03 /pmc/articles/PMC7744418/ /pubmed/33343376 http://dx.doi.org/10.3389/fphar.2020.605185 Text en Copyright © 2020 Monti, Vertogen, Masini, Donati, Lilli, Zingaretti, Musuraca, De Giorgi, Cerchione, Farolfi, Cortesi, Viale, Martinelli and Nanni http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Monti, Manuela
Vertogen, Bernadette
Masini, Carla
Donati, Caterina
Lilli, Claudia
Zingaretti, Chiara
Musuraca, Gerardo
De Giorgi, Ugo
Cerchione, Claudio
Farolfi, Alberto
Cortesi, Pietro
Viale, Pierluigi
Martinelli, Giovanni
Nanni, Oriana
Hydroxychloroquine as Prophylaxis for COVID-19: A Review
title Hydroxychloroquine as Prophylaxis for COVID-19: A Review
title_full Hydroxychloroquine as Prophylaxis for COVID-19: A Review
title_fullStr Hydroxychloroquine as Prophylaxis for COVID-19: A Review
title_full_unstemmed Hydroxychloroquine as Prophylaxis for COVID-19: A Review
title_short Hydroxychloroquine as Prophylaxis for COVID-19: A Review
title_sort hydroxychloroquine as prophylaxis for covid-19: a review
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744418/
https://www.ncbi.nlm.nih.gov/pubmed/33343376
http://dx.doi.org/10.3389/fphar.2020.605185
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