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All Studies   Meta Analysis    Recent:   

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial

Gautret et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.105949 (date from preprint)
Mar 2020  
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Virological cure at day 6 66% Improvement Relative Risk HCQ for COVID-19  Gautret et al.  EARLY TREATMENT Is early treatment with HCQ beneficial for COVID-19? Prospective study of 36 patients in France Improved viral clearance with HCQ (p=0.001) c19hcq.org Gautret et al., Int. J. Antimicrobial .., Mar 2020 FavorsHCQ Favorscontrol 0 0.5 1 1.5 2+
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
 
*, now with p < 0.00000000001 from 418 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
5,000+ studies for 104 treatments. c19hcq.org
HCQ was significantly associated with reduction / elimination of viral load, which was enhanced with AZ. Updated 8/13: responses to this paper have raised methodological issues1-3.
Despite the limitations, this early observational study was a milestone in the discovery process, including detailed daily evolution of PCR positivity. This study should be viewed in the context of the series of studies from this group.
An update to this paper, including originally excluded patients, confirms the effectiveness of HCQ+AZ on viral clearance and early discharge4. Also see5 and the response from the authors6.
This study is excluded in the after exclusion results of meta analysis: excessive unadjusted differences between groups; results only for PCR status which may be significantly different to symptoms.
risk of no virological cure at day 6, 66.0% lower, RR 0.34, p = 0.001, treatment 6 of 20 (30.0%), control 14 of 16 (87.5%), NNT 1.7.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Gautret et al., 17 Mar 2020, prospective, France, peer-reviewed, 18 authors, average treatment delay 4.1 days, dosage 200mg tid days 1-10.
This PaperHCQAll
Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial
Philippe Gautret, Jean-Christophe Lagier, Philippe Parola, Van Thuan Hoang, Line Meddeb, Morgane Mailhe, Barbara Doudier, Johan Courjon, Valérie Giordanengo, Vera Esteves Vieira, Hervé Tissot Dupont, Stéphane Honoré, Philippe Colson, Eric Chabrière, Bernard La Scola, Jean-Marc Rolain, Philippe Brouqui, Didier Raoult
International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.105949
Background: Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the effect of hydroxychloroquine on respiratory viral loads. Patients and methods: French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16 th , to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point. Results: Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported in the litterature for untreated patients. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination. Conclusion: Despite its small sample size, our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.
Declarations Supplementary material Supplementary material associated with this article can be found, in the online version, at doi: 10.1016/j.ijantimicag.2020. 105949 .
References
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Armstrong, Richez, Raoult, Chabriere, Simultaneous UHPLC-UV analysis of hydroxychloroquine, minocycline and doxycycline from serum samples for the therapeutic drug monitoring of Q fever and Whipple's disease, B Analyt. Technol. Biomed. Life Sci
Bacharier, Guilbert, Mauger, Boehmer, Beigelman et al., Early administration of azithromycin and prevention of severe lower respiratory tract illnesses in preschool children with a history of such illnesses: A randomized clinical trial, JAMA, doi:10.1001/jama.2015.13896
Biot, Daher, Chavain, Fandeur, Khalife et al., Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities, J Med Chem
Bosseboeuf, Aubry, Nhan, De Pina, Rolain et al., Azithromycin inhibits the replication of Zika virus, J Antivirals Antiretrovirals, doi:10.4172/1948-5964.1000173
Colson, Rolain, Lagier, Brouqui, Raoult, Chloroquine and hydroxychloroquine as available weapons to fight COVID-19, Int J Antimicrob Agents
Colson, Rolain, Raoult, Chloroquine for the 2019 novel coronavirus SARS-CoV-2, Int J Antimicrob Agents, doi:10.1016/j.ijantimicag.2020.105923
Gao, Tian, Yang, Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies, Biosci Trends, doi:10.5582/bst.2020.01047
Lagier, Raoult, Whipple's disease and Tropheryma whipplei infections: when to suspect them and how to diagnose and treat them, Zhonghua Jie He He Hu Xi Za Zhi, doi:10.1097/QCO.0000000000000489
Lai, Shih, Ko, Tang, Hsueh, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges, Int J Antimicrob Agents, doi:10.1016/j.ijantimicag.2020.105924
Madrid, Panchal, Warren, Shurtleff, Endsley et al., Evaluation of Ebola Virus Inhibitors for Drug Repurposing, ACS Infect Dis, doi:10.1021/acsinfecdis.5b00030
Marmor, Kellner, Lai, Melles, Mieler et al., Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision), Ophthalmology Jun, doi:10.1016/j.ophtha.2016.01.058
Raoult, Houpikian, Dupont, Riss, Arditi-Djiane et al., Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine, Arch Intern Med
Retallack, Lullo, Arias, Knopp, Laurie et al., Zika virus cell tropism in the developing human brain and inhibition by azithromycin, Proc Natl Acad Sci U S A
Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res
Wang, Wang, Ye, Liu, A review of the 2019 Novel Coronavirus (COVID-19) based on current evidence, Int J Antimicrob Agents
Wu, Mcgoogan, Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention, JAMA, doi:10.1001/jama.2020.2648
Yao, Ye, Zhang, Cui, Huang et al., Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Clin Infect Dis, doi:10.1093/cid/ciaa237
Zhou, Yu, Du, Fan, Liu et al., Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, Lancet, doi:10.1016/S0140-6736(20)30566-3
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