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0 0.5 1 1.5 2+ Mortality -9% Improvement Relative Risk Ventilation -15% HCQ  RECOVERY  LATE TREATMENT  RCT Is late treatment with HCQ beneficial for COVID-19? RCT 4,716 patients in the United Kingdom (March - June 2020) No significant difference in outcomes seen RECOVERY Collaborative Group, NEJM, Jun 2020 Favors HCQ Favors control

Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial

RECOVERY Collaborative Group, NEJM, doi:10.1056/NEJMoa2022926 (press release 6/5), RECOVERY, NCT04381936
Jun 2020  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
*, now known with p < 0.00000000001 from 422 studies, recognized in 42 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,000+ studies for 60+ treatments.
RECOVERY trial finds no significant benefit for very late stage (9 days after symptom onset) very sick patients. Results may be due to the unusually high dosage used (9.2g total over 10 days), (B).
The overall dosage used is only 23% less than the high dosage that Borba et al. show greatly increases risk (OR 2.8) Borba.
Authors do not report results based on weight, BMI, or related conditions such as diabetes, which may provide additional evidence of toxic dosages. Authors do not adjust dosage based on patient weight, so toxicity may be higher in patients of lower weight.
KM curves show a spike in HCQ mortality days 5-8, corresponding to ~85% of the total excess seen at day 28 (a similar spike is seen in the SOLIDARITY trial).
Authors note: "we did not observe excess mortality in the first 2 days of treatment ... when early effects of dose-dependent toxicity might be expected", but they are ignoring the very long half-life of HCQ and the dosing regimen - much higher levels of HCQ will be reached later. Increased mortality in Borba et al. occurred after 2 days.
Patients were extremely sick (median 9 days post symptoms, 60% requiring oxygen and an additional 17% requiring ventilation/ECMO), with an unusually high mortality rate was seen in both arms. 1,561 HCQ patients, 3,155 SOC.
A secondary analysis has found several inconsistencies in the data: Hypoxia may inhibit HCQ entering cells (C), making it less effective for late stage use. For more on the dosing problems see, also noting that concentrations vary substantially in different tissues and lung concentration may be >30x plasma concentration.
This study is excluded in the after exclusion results of meta analysis: excessive dosage in late stage patients, results do not apply to typical dosages.
risk of death, 9.0% higher, RR 1.09, p = 0.15, treatment 421 of 1,561 (27.0%), control 790 of 3,155 (25.0%).
risk of mechanical ventilation, 15.0% higher, RR 1.15, p = 0.19, treatment 128 of 1,300 (9.8%), control 225 of 2,623 (8.6%).
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
RECOVERY Collaborative Group et al., 5 Jun 2020, Randomized Controlled Trial, United Kingdom, preprint, baseline oxygen required 76.8%, 29 authors, study period 25 March, 2020 - 5 June, 2020, average treatment delay 9.0 days, trial NCT04381936 (history) (RECOVERY).
This PaperHCQAll
Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19
Peter Horby, M.D Marion Mafham, Louise Linsell, D Phil, M.Sc Jennifer L Bell, Ph.D Natalie Staplin, Ph.D Jona- Than R Emberson, Ph.D Martin Wiselka, Ph.D Andrew Ustianowski, Einas Elmahi, M Phil, Benjamin Prudon, Tony Whitehouse, Ph.D Timothy Fel- Ton, John Williams, M.D Jakki Faccenda, Ph.D Jonathan Underwood, M.D J Kenneth Baillie, Ph.D Lucy C Chappell, Ph.D Saul N Faust, F.R.C.P.C.H Thomas Jaki, Ph.D Katie Jeffery, Ph.D Wei Shen Lim, Ph.D Alan Montgomery, Ph.D Kathryn Rowan, Ph.D Joel Tarning, James A Wat- Son, Nicholas J White, M.Sc Ed- Mund Juszczak, Richard Haynes, Ph.D Martin J Landray, Mafham Drs Horby, Prof Linsell Juszczak, Dr Haynes, Dr Landray
New England Journal of Medicine, doi:10.1056/nejmoa2022926
This is the New England Journal of Medicine version of record, which includes all Journal editing and enhancements. The Author Final Manuscript, which is the author's version after external peer review and before publication in the Journal, is available under a CC BY license at PMC7556338.
A data sharing statement provided by the authors is available with the full text of this article at We thank the thousands of patients who participated in this trial; the doctors, nurses, pharmacists, other allied health professionals, and research administrators at 176 NHS hospitals across the United Kingdom who were assisted by the NIHR Clinical Research Network, NHS DigiTrials, Public Health England, the Department of Health and Social Care, the Intensive Care National Audit and Research Centre, Public Health Scotland, National Records Service of Scotland, the Secure Anonymised Information Linkage at University of Swansea, and the NHS in England, Scotland, Wales, and Northern Ireland; and the members of the independent data monitoring committee: Peter Sandercock, Janet Darbyshire, David DeMets, Robert Fowler, David Lalloo, Ian Roberts, and Janet Wittes. Appendix The authors' full names and academic degrees are as follows: The RECOVERY Collaborative GroupPeter Horby, F.
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Late treatment
is less effective
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