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  3. Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data
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Research

Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data

BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1844 (Published 14 May 2020) Cite this as: BMJ 2020;369:m1844

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Lack of efficacy of hydroxychloroquine in covid-19

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  1. Matthieu Mahévas, professor1,
  2. Viet-Thi Tran, associate professor2,
  3. Mathilde Roumier, doctor3,
  4. Amélie Chabrol, doctor4,
  5. Romain Paule, doctor3,
  6. Constance Guillaud, doctor1,
  7. Elena Fois, doctor1,
  8. Raphael Lepeule, doctor5,
  9. Tali-Anne Szwebel, doctor6,
  10. François-Xavier Lescure, professor7,
  11. Frédéric Schlemmer, associate professor8,
  12. Marie Matignon, doctor9,
  13. Mehdi Khellaf, professor1,
  14. Etienne Crickx, doctor1,
  15. Benjamin Terrier, professor6,
  16. Caroline Morbieu, doctor6,
  17. Paul Legendre, doctor6,
  18. Julien Dang, fellow2,
  19. Yoland Schoindre, doctor3,
  20. Jean-Michel Pawlotsky, professor10,
  21. Marc Michel, professor1,
  22. Elodie Perrodeau, biostatistician2,
  23. Nicolas Carlier, doctor11,
  24. Nicolas Roche, professor11,
  25. Victoire de Lastours, professor12,
  26. Clément Ourghanlian, pharmacist13,
  27. Solen Kerneis, doctor14,
  28. Philippe Ménager, doctor15,
  29. Luc Mouthon, professor6,
  30. Etienne Audureau, professor16,
  31. Philippe Ravaud, professor2,
  32. Bertrand Godeau, professor1,
  33. Sébastien Gallien, professor17,
  34. Nathalie Costedoat-Chalumeau, professor2 6
  1. 1Department of Internal Medicine, Henri-Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Est Créteil University, 51 avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France
  2. 2Centre for Clinical Epidemiology, Hôtel-Dieu Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris, Centre of Research in Epidemiology and Statistics, Paris, France
  3. 3Department of Internal Medicine, Foch Hospital, Suresnes, France
  4. 4Department of Infectious Diseases, Sud Francilien Hospital, Corbeil-Essonnes, France
  5. 5Transversal Infections Treatment Unit, Henri-Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Est Créteil University, Créteil, France
  6. 6Department of Internal Medicine, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris, Paris, France
  7. 7Department of Infectious Diseases, Hôpital Bichat Hospital, Paris, France
  8. 8Pulmonology Unit, Henri-Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Est Créteil University, Créteil, France
  9. 9Department of Nephrology, Henri-Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Est Créteil University, Créteil, France
  10. 10Department of Virology, Bacteriology-Hygiene, and Mycology-Parasitology Centre, Henri-Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
  11. 11Department of Pulmonology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris, Paris, France
  12. 12Department of Internal Medicine, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris, Paris, France
  13. 13Pharmacy, Henri-Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Est Créteil University, Créteil, France
  14. 14Mobile Infectious Disease Team, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris, Paris, France
  15. 15Pulmonology Unit, Sud Francilien Hospital, Corbeil-Essonnes, France
  16. 16Clinical Epidemiology and Aging Team, Mondor Institute for Biomedical Research (INSERM U955), Public Health Services, Henri-Mondor Hosptial, Assistance Publique-Hôpitaux de Paris, Paris-Est Créteil University, Créteil, France
  17. 17Department of Infectious Diseases, Henri-Mondor Hospital, Assistance Publique-Hôpitaux de Pari, Paris-Est Créteil University, Créteil, France
  1. Correspondence to: M Mahévas matthieu.mahevas{at}gmail.com
  • Accepted 5 May 2020

Abstract

Objective To assess the effectiveness of hydroxychloroquine in patients admitted to hospital with coronavirus disease 2019 (covid-19) pneumonia who require oxygen.

Design Comparative observational study using data collected from routine care.

Setting Four French tertiary care centres providing care to patients with covid-19 pneumonia between 12 March and 31 March 2020.

Participants 181 patients aged 18-80 years with documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who required oxygen but not intensive care.

Interventions Hydroxychloroquine at a dose of 600 mg/day within 48 hours of admission to hospital (treatment group) versus standard care without hydroxychloroquine (control group).

Main outcome measures The primary outcome was survival without transfer to the intensive care unit at day 21. Secondary outcomes were overall survival, survival without acute respiratory distress syndrome, weaning from oxygen, and discharge from hospital to home or rehabilitation (all at day 21). Analyses were adjusted for confounding factors by inverse probability of treatment weighting.

Results In the main analysis, 84 patients who received hydroxychloroquine within 48 hours of admission to hospital (treatment group) were compared with 89 patients who did not receive hydroxychloroquine (control group). Eight additional patients received hydroxychloroquine more than 48 hours after admission. In the weighted analyses, the survival rate without transfer to the intensive care unit at day 21 was 76% in the treatment group and 75% in the control group (weighted hazard ratio 0.9, 95% confidence interval 0.4 to 2.1). Overall survival at day 21 was 89% in the treatment group and 91% in the control group (1.2, 0.4 to 3.3). Survival without acute respiratory distress syndrome at day 21 was 69% in the treatment group compared with 74% in the control group (1.3, 0.7 to 2.6). At day 21, 82% of patients in the treatment group had been weaned from oxygen compared with 76% in the control group (weighted risk ratio 1.1, 95% confidence interval 0.9 to 1.3). Eight patients in the treatment group (10%) experienced electrocardiographic modifications that required discontinuation of treatment.

Conclusions Hydroxychloroquine has received worldwide attention as a potential treatment for covid-19 because of positive results from small studies. However, the results of this study do not support its use in patients admitted to hospital with covid-19 who require oxygen.

Footnotes

  • Contributors: VTT and MR contributed equally to the work. MMah conceptualised the paper. MMah, MR, AC, RP, CG, SG, RL, TAS, FS, MMat, MK, EC, BT, CM, PL, YS, MMic, EP, NC, NR, VdL, LM, FXL, EA, PM, EF, CO, SK, and NCC collected data. VTT, JD, EP, and PR analysed data. JMP performed SARS-Cov2 RT-PCR. MMah, VTT, PR, BG, and NCC interpreted the results and wrote the article. All authors contributed to revision of the final version of the manuscript, approved the final version submitted, and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. MMah acts as guarantor for the work. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding: No funding received for the present study.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; EA reports personal fees from GBT, personal fees from Hemanext, outside the submitted work; NC reports non-financial support from Novartis, non-financial support from Mylan, non-financial support from Therakos, outside the submitted work; AC reports non-financial support from Sanofi, non-financial support from Janssen, outside the submitted work; NCC reports grants from GlaxoSmithKline (GSK), grants from UCB, outside the submitted work; EC has nothing to disclose; JD has nothing to disclose; SG reports personal fees and non-financial support from Gilead Sciences, personal fees and non-financial support from ViiV Healthcare SAS, other from Sanofi Aventis France, personal fees, non-financial support and other from Pfizer SAS, personal fees from Icomed, other from OVERCOME, personal fees and non-financial support from MSD France, non-financial support from Mylan Medical SAS, non-financial support from CSL Behring SA, personal fees and non-financial support from Janssen-Cilag, non-financial support from Longueur D’Ondes, non-financial support from Octapharma France, outside the submitted work; VdL reports non-financial support from Eumedica, non-financial support from Fresenuis Kabi, outside the submitted work; EF reports personal fees from Novartis, outside the submitted work; BG reports grants and personal fees from Amgen, personal fees from Novartis, grants and personal fees from Roche, personal fees from Grifols, personal fees from LFB, outside the submitted work; CG has nothing to disclose; SK reports personal fees from Accelerate Diagnostics, other from Astellas, grants, personal fees and other from bioMérieux, personal fees and other from MSD, other from Pfizer, personal fees from Menarini, outside the submitted work; MK has nothing to disclose; PL has nothing to disclose; FXL has received personal fees from Gilead and MSD; RL reports non-financial support from Eumedica SA, non-financial support from Gilead Sciences, non-financial support from MSD France, non-financial support from Pfizer PFE France, non-financial support from Sanofi Aventis France, non-financial support from Astellas Pharma, non-financial support from CSL Behring SA, non-financial support from Ipsen Pharma, outside the submitted work; MMah reports grants from GSK, other from GSK, other from Morphosys, personal fees from LFB, personal fees from Amgen, personal fees from Grifols, outside the submitted work; MMat reports personal fees from A+A, personal fees from CSL Behring, personal fees from ELIVIE, personal fees from Genzyme, personal fees from Vivactis, outside the submitted work; PM has nothing to disclose; MMic reports personal fees from Alexion, personal fees from Amgen, personal fees from Novartis, personal fees from Argenx, personal fees from Sanofi-Bioverativ, outside the submitted work; CM reports non-financial support from Novartis, outside the submitted work; LM reports personal fees from Janssen Cilag, non-financial support from Swedish orphan biovitrum, non-financial support from LFB, non-financial support from Shire, non-financial support from Grifols, outside the submitted work; CO reports non-financial support from MSD, non-financial support from Janssen, non-financial support from CSL Behring, non-financial support from Gilead, outside the submitted work; RP has nothing to disclose; JMP reports personal fees from Abbvie, personal fees from Gilead, personal fees from Merck, personal fees from Siemens Healthcare, outside the submitted work; EP has nothing to disclose; PR reports personal fees from Inato, outside the submitted work; NR reports grants and personal fees from Boehringer Ingelheim, grants and personal fees from Novartis, personal fees from Teva, personal fees from GSK, personal fees from AstraZeneca, personal fees from Chiesi, grants and personal fees from Pfizer, personal fees from Sanofi, personal fees from Zambon, outside the submitted work; MR reports personal fees from Novartis Pharma SAS, personal fees from Bristol Myers Squibb, personal fees from Swedish Orphan Biovitrum, outside the submitted work; FS reports personal fees from Gilead Sciences, outside the submitted work; YS reports non-financial support from AstraZeneca, non-financial support from Novartis Pharma, non-financial support from Bristol Myers Squibb, non-financial support from Sanofi Aventis France, non-financial support from Shire France, non-financial support from Chugai Pharma France, non-financial support from Pfizer SAS, non-financial support from Swedish Orphan Biovitrum, non-financial support from CSL Behring SA, outside the submitted work; TAS reports personal fees from Bayer, non-financial support from LFB, non-financial support from Medexact, non-financial support from Mundipharma, outside the submitted work; BT reports personal fees from AstraZeneca, personal fees from Roche Chugai, personal fees from GSK, grants from Bristol Myers Squibb, grants from Lilly, grants from Vifor Pharma, outside the submitted work; VTT has nothing to disclose; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the ethics committee of Henri-Mondor Hospital, AP-HP (No 2020_060). Patients were informed by letter of the use of their data.

  • Data sharing: The data are available on request.

  • Dissemination to related patient and public communities: We plan to issue a press release on official publication of this manuscript and disseminate our findings through social media outlets, to ensure the results of the study have a broad public outreach.

  • The lead author (MMah) affirms that the 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 have been explained.

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