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0 0.5 1 1.5 2+ Case 42% Improvement Relative Risk HCQ for COVID-19  Wiseman et al.  META ANALYSIS Favors HCQ Favors control

Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data

Wiseman et al., medRxiv, doi:10.1101/2020.11.29.20235218
Dec 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.
6th independent analysis showing efficacy from the Boulware PEP trial. This prospective analysis corrects an error in the NEJM paper where shipping delays are omitted (still not corrected).
42% reduction in COVID-19 (9.6% vs. 16.5%), RR 0.58 [0.35 - 0.97], p=0.044, for the original trial 3 day specification.
7 meta analyses show significant improvements with hydroxychloroquine for mortality Landsteiner de Sampaio Amêndola, Risch, Risch (B), Stricker, hospitalization Landsteiner de Sampaio Amêndola, recovery Prodromos, combined death/hospitalization/cases Ladapo, and cases García-Albéniz.
Currently there are 8 HCQ for COVID-19 post-exposure prophylaxis studies, showing 46% lower mortality [-80‑84%], 16% lower hospitalization [-69‑58%], and 25% fewer cases [-0‑43%].
risk of case, 42.0% lower, RR 0.58, p = 0.04, <= 3 days after exposure.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Wiseman et al., 2 Dec 2020, preprint, 4 authors.
This PaperHCQAll
Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data
PhD, MRPharmS David M Wiseman, MD Pierre Kory, PhD, MB Samir A Saidi, PhD. d Dan Mazzucco
BACKGROUND: A key trial (NCT04308668) of post-exposure prophylaxis found hydroxychloroquine-associated (HCQ) reductions of Covid-19 by 17% overall and 31% to 49% in subgroups. To understand these trends, we reanalyzed the dataset. METHODS: Our protocol conformed to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT). We compared the incidence of Covid-19 after HCQ or placebo, stratifying by intervention lag, age, and gender. RESULTS: Newly requested data missing from the dataset revealed that 52% and 19% of subjects received medication 1-2 days after intended and assumed overnight delivery or four-day intervention lag respectively. After re-analysis, we found reduced HCQ-associated incidence of Covid-19 with Early (up to 3 days post-exposure) (RR 0.58, 95%CI 0.35 -0.97; p=0.044; NNT 14.5) but not Late (RR 1.22, 95%CI 0.72 -2.04) prophylaxis. We found a significant HCQ-associated Covid-19 reduction in subjects 18 to 45 years old with Early (RR 0.54, 95%CI 0.29-0.97; p=0.0448, NNT 11.5) but not Late (RR 1.02, 95%CI 0.55-1.89) prophylaxis, attenuated in older subjects (RR 0.75, 95%CI 0-27-2.05) and by co-morbidities. Although, we did not detect effects of gender, folate, zinc, or ascorbate, confounding effects cannot be excluded. CONCLUSIONS: Using novel data and prospective re-analysis, hydroxychloroquine, in an age-dependent manner, was associated with reduced Covid-19 compatible illness when supplied for post-exposure prophylaxis between 1 and 3 days after high-or moderate-risk exposure, at higher loading and maintenance doses than in similar studies. The original study conclusions are controverted, and our finding warrants prospective confirmation.
Conflicts of Interest The sponsor is entirely responsible for its design and conduct. The sponsor and principal investigator have no financial or other conflicts of interest in the subject matter of this study. DMW is the president of Synechion, Inc. and KevMed, LLC, providing services for the medical industry and marketing medical products, respectively, outside of the area of this work. See ICMJE forms for further details. DM is the president of ZSX Medical, LLC. developing surgical devices and a Principal at Third Eye Associates, a technical consulting company. PK and SAS report no conflicts. Data Sharing Microsoft Excel files will be available on reasonable request up to one year after publication to qualified investigators subject to an agreed upon data sharing agreement. The source dataset is available from the original authors.
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