Hydroxychloroquine with or without azithromycin and in-hospital mortality or discharge in patients hospitalized for COVID-19 infection: a cohort study of 4,642 in-patients in France

Sbidian et al., medRxiv, doi:10.1101/2020.06.16.20132597

Jun 2020

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Retrospective of 4,642 hospitalized patients in France showing significantly faster discharge with HCQ and HCQ+AZ. No significant effect is seen on 28-day mortality, however many more control patients are still in hospital at 28 days. Other studies show faster resolution for HCQ, suggesting there will be a significant improvement when extending past 28 days. Hopefully authors will extend the analysis. Note that the median age is higher in the group not treated with HCQ or AZ.

For other issues with the adjustments see medrxiv.org. Also see the analysis here twitter.com.

This study is excluded in the after exclusion results of meta analysis: significant issues found with adjustments.

1. medrxiv.org, www.medrxiv.org/content/10.1101/2020.06.16.20132597v1#disqus_thread.www.medrxiv.org/content/10.1101/2020.06.16.20132597v1#disqus_thread.

2. twitter.com, twitter.com/Covid19Crusher/status/1274668697408471040.twitter.com/Covid19Crusher/status/1274668697408471040.

Important missing comments or errors? Let us know.

risk of death, 5.0% higher, RR 1.05, p = 0.74, treatment 111 of 623 (17.8%), control 830 of 3,792 (21.9%), adjusted per study, whole population HCQ AIPTW adjusted.

risk of no hospital discharge, 20.0% lower, RR 0.80, p = 0.002, treatment 623, control 3,792, adjusted per study, inverted to make RR<1 favor treatment, whole population HCQ AIPTW adjusted.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Sbidian et al., 19 Jun 2020, retrospective, database analysis, France, preprint, 21 authors.

All Studies Meta Analysis Submit Updates or Corrections

This Paper HCQ All

Hydroxychloroquine with or without azithromycin and in-hospital mortality or discharge in patients hospitalized for COVID-19 infection: a cohort study of 4,642 in-patients in France

Emilie Sbidian, Julie Josse, Guillaume Lemaitre, Imke Meyer, Mélodie Bernaux, Alexandre Gramfort, Nathanaël Lapidus, Nicolas Paris, Antoine Neuraz, Ivan Lerner, Nicolas Garcelon, Bastien Rance, Olivier Grisel, Thomas Moreau, Ali Bellamine, Pierre Wolkenstein, Gaël Varoquaux, Eric Caumes, Marc Lavielle, Armand Mekontso Dessap, Etienne Audureau

doi:10.1101/2020.06.16.20132597

Data sharing The data are available on request. Transparency The manuscript's guarantors (ES) affirm that this manuscript is an honest, accurate and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Abbreviations: SD, Standard deviation; HCQ:hydroxychloroquine, IQR : interquartile 25

References

Aluvaala, Collins, Maina, Competing risk survival analysis of time to inhospital death or discharge in a large urban neonatal unit in Kenya, Wellcome Open Res, doi:10.12688/wellcomeopenres.15302.1

Athey, Tibshirani, Wager, Generalized random forests, Ann Stat, doi:10.1214/18-AOS1709

Austin, An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies, Multivar Behav Res, doi:10.1080/00273171.2011.568786

Austin, Stuart, Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies, Stat Med, doi:10.1002/sim.6607

Beigel, Tomashek, Dodd, Remdesivir for the Treatment of Covid-19 -Preliminary Report, N Engl J Med, doi:10.1056/NEJMoa2007764

Benichou, Gail, Estimates of absolute cause-specific risk in cohort studies, Biometrics

Camprubí-Rimblas, Tantinyà, Bringué, Guillamat-Prats, Artigas, Anticoagulant therapy in acute respiratory distress syndrome, Ann Transl Med, doi:10.21037/atm.2018.01.08

Chen, Hu, Zhang, Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. medRxiv, doi:10.1101/2020.03.22.20040758

Delvecchio, Higa, Pezzuto, Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models, Viruses, doi:10.3390/v8120322

Dm, Drug-induced Prolongation of the QT Interval, The New England journal of medicine, doi:10.1056/NEJMra032426

Funk, Westreich, Wiesen, Stürmer, Brookhart et al., Doubly robust estimation of causal effects, Am J Epidemiol, doi:10.1093/aje/kwq439

Gautret, Lagier, Parola, Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study, Travel Med Infect Dis. Published online, doi:10.1016/j.tmaid.2020.101663

Gautret, Lagier, Parola, Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int J Antimicrob Agents, doi:10.1016/j.ijantimicag.2020.105949

Geleris, Sun, Platt, Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19, N Engl J Med. Published online, doi:10.1056/NEJMoa2012410

Goyal, Choi, Pinheiro, Clinical Characteristics of Covid-19 in New York City, N Engl J Med. Published online, doi:10.1056/NEJMc2010419

Guan, Ni, Hu, Clinical Characteristics of Coronavirus Disease 2019 in China, N Engl J Med. Published online, doi:10.1056/NEJMoa2002032

Hamon, Grabar, Linguistic approach for identification of medication names and related information in clinical narratives, J Am Med Inform Assoc JAMIA, doi:10.1136/jamia.2010.004036

Lacticodeshydrogenase, None, median

Magagnoli, Narendran, Pereira, Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. medRxiv, doi:10.1101/2020.04.16.20065920

Mahévas, Tran, Roumier, Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data, The BMJ, doi:10.1136/bmj.m1844

Mehra, Desai, Ruschitzka, Patel, Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis, The Lancet, doi:10.1016/S0140-6736(20)31180-6

Mercuro, Yen, Shim, Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19), JAMA Cardiol. Published online, doi:10.1001/jamacardio.2020.1834

Million, Lagier, Gautret, Full-length title: Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France, Travel Med Infect Dis. Published online, doi:10.1016/j.tmaid.2020.101738

Ozenne, Scheike, Staerk, Gerds, On the estimation of average treatment effects with right-censored time to event outcome and competing risks, Published online, doi:10.1002/bimj.201800298

Resche-Rigon, Azoulay, Chevret, Evaluating mortality in intensive care units: contribution of competing risks analyses, Crit Care, doi:10.1186/cc3921

Rosenbaum, Db, Reducing Bias in Observational Studies Using Subclassification on the Propensity Score, J Am Stat Assoc, doi:10.2307/2288398

Rosenbaum, Db, The Central Role of the Propensity Score in Observational Studies for Causal Effects, Biometrika, doi:10.2307/2335942

Rosenberg, Dufort, Udo, Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State, JAMA. Published online, doi:10.1001/jama.2020.8630

Textor, Hardt, Knüppel, DAGitty: a graphical tool for analyzing causal diagrams

Villar, Ferrando, Martínez, Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial, Lancet Respir Med, doi:10.1016/S2213-2600(19)30417-5

Wendling, Jung, Callahan, Schuler, Shah et al., Comparing methods for estimation of heterogeneous treatment effects using observational data from health care databases, Stat Med, doi:10.1002/sim.7820

Yao, Ye, Zhang, 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 Off Publ Infect Dis Soc Am, doi:10.1093/cid/ciaa237

Late treatment
is less effective

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