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...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-12-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.605185/full |
| _version_ | 1818352030876434432 |
|---|---|
| author | Manuela Monti Bernadette Vertogen Carla Masini Caterina Donati Claudia Lilli Chiara Zingaretti Gerardo Musuraca Ugo De Giorgi Claudio Cerchione Alberto Farolfi Pietro Cortesi Pierluigi Viale Giovanni Martinelli Oriana Nanni |
| author_facet | Manuela Monti Bernadette Vertogen Carla Masini Caterina Donati Claudia Lilli Chiara Zingaretti Gerardo Musuraca Ugo De Giorgi Claudio Cerchione Alberto Farolfi Pietro Cortesi Pierluigi Viale Giovanni Martinelli Oriana Nanni |
| author_sort | Manuela Monti |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T18:47:10Z |
| format | Article |
| id | doaj.art-5e5d2500b28a41b0b95df5b3db729663 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T18:47:10Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-5e5d2500b28a41b0b95df5b3db7296632022-12-21T23:35:02ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-12-011110.3389/fphar.2020.605185605185Hydroxychloroquine as Prophylaxis for COVID-19: A ReviewManuela Monti0Bernadette Vertogen1Carla Masini2Caterina Donati3Claudia Lilli4Chiara Zingaretti5Gerardo Musuraca6Ugo De Giorgi7Claudio Cerchione8Alberto Farolfi9Pietro Cortesi10Pierluigi Viale11Giovanni Martinelli12Oriana Nanni13Istituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori (IRST) IRCCS, Meldola, ItalyIstituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori (IRST) IRCCS, Meldola, ItalyIstituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori (IRST) IRCCS, Meldola, ItalyIstituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori (IRST) IRCCS, Meldola, ItalyIstituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori (IRST) IRCCS, Meldola, ItalyIstituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori (IRST) IRCCS, Meldola, ItalyIstituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori (IRST) IRCCS, Meldola, ItalyIstituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori (IRST) IRCCS, Meldola, ItalyIstituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori (IRST) IRCCS, Meldola, ItalyIstituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori (IRST) IRCCS, Meldola, ItalyIstituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori (IRST) IRCCS, Meldola, ItalyDipartimento di Scienze Mediche e Chirugiche, Università di Bologna, Bologna, ItalyIstituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori (IRST) IRCCS, Meldola, ItalyIstituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori (IRST) IRCCS, Meldola, ItalyThe 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.https://www.frontiersin.org/articles/10.3389/fphar.2020.605185/fullhydroxychloroquineprophylaxisCOVID-19reviewclinical trials |
| spellingShingle | Manuela Monti Bernadette Vertogen Carla Masini Caterina Donati Claudia Lilli Chiara Zingaretti Gerardo Musuraca Ugo De Giorgi Claudio Cerchione Alberto Farolfi Pietro Cortesi Pierluigi Viale Giovanni Martinelli Oriana Nanni Hydroxychloroquine as Prophylaxis for COVID-19: A Review Frontiers in Pharmacology hydroxychloroquine prophylaxis COVID-19 review clinical trials |
| 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 | hydroxychloroquine prophylaxis COVID-19 review clinical trials |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2020.605185/full |
| work_keys_str_mv | AT manuelamonti hydroxychloroquineasprophylaxisforcovid19areview AT bernadettevertogen hydroxychloroquineasprophylaxisforcovid19areview AT carlamasini hydroxychloroquineasprophylaxisforcovid19areview AT caterinadonati hydroxychloroquineasprophylaxisforcovid19areview AT claudialilli hydroxychloroquineasprophylaxisforcovid19areview AT chiarazingaretti hydroxychloroquineasprophylaxisforcovid19areview AT gerardomusuraca hydroxychloroquineasprophylaxisforcovid19areview AT ugodegiorgi hydroxychloroquineasprophylaxisforcovid19areview AT claudiocerchione hydroxychloroquineasprophylaxisforcovid19areview AT albertofarolfi hydroxychloroquineasprophylaxisforcovid19areview AT pietrocortesi hydroxychloroquineasprophylaxisforcovid19areview AT pierluigiviale hydroxychloroquineasprophylaxisforcovid19areview AT giovannimartinelli hydroxychloroquineasprophylaxisforcovid19areview AT orianananni hydroxychloroquineasprophylaxisforcovid19areview |