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All Studies   Meta Analysis    Recent:   

Outcomes of Persons With COVID-19 in Hospitals With and Without Standard Treatment With (Hydroxy)chloroquine

Peters et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.10.004 (date from preprint)
Aug 2020  
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Mortality -9% Improvement Relative Risk HCQ for COVID-19  Peters et al.  LATE TREATMENT Is late treatment with HCQ beneficial for COVID-19? Retrospective 1,949 patients in Netherlands No significant difference in mortality c19hcq.org Peters et al., Clinical Microbiology a.., Aug 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 411 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19hcq.org
Retrospective study of HCQ use in 9 hospitals in the Netherlands, showing no significant difference in mortality with HCQ/CQ or dexamethasone. Late stage (admitted to hospital with positive test or CT scan abnormalities). 4 of 7 hospitals started treatment only after further deterioration. Short cutoff (21 days) - other studies have shown treated patient cases resolved faster and more control patients remaining in hospital at this time.
In the preprint, 58 of 341 control patients died. In the journal version, 53 of 353 control patients died.
Significant differences between hospitals - HCQ hospitals had significantly older patients with significantly more comorbidities. Non-HCQ hospitals were "tertiary academic centres" whereas HCQ hospitals were "secondary care hospitals". Residual confounding likely. This study compares overcrowded regular hospitals with undercrowded academic hospitals.
A subset of patients were excluded due to transfer to other hospitals. This introduces bias because patients in critical condition are not transferred. For examples, patients benefiting from HCQ treatment may have been transferred to the tertiary centres and excluded from analysis, increasing the percentage of critical cases in the secondary hospitals.
Among the seven (H)CQ-hospitals, the timing of start of (H)CQ treatment differed; three hospitals started at the moment of COVID-19 diagnosis, four started after diagnosis but only when patients clinically deteriorated e.g., when there was an increase in respiratory rate or increase in use of supplemental oxygen.
Most patients received CQ instead of the safer HCQ, receiving late treatment with CQ. Patients were given an initial dose of 600mg CQ then every 12 hours, for 5 days a dose of 300 mg, for a total of 3600mg CQ. This dose is likely to be toxic, see for example1.
Authors mention a subset of hospitals started treatment relatively earlier, which seems like the most important area to analyze, but no results are provided.
This study is excluded in the after exclusion results of meta analysis: excessive unadjusted differences between groups.
risk of death, 9.0% higher, HR 1.09, p = 0.57, treatment 419 of 1,596 (26.3%), control 53 of 353 (15.0%), adjusted per study.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Peters et al., 15 Aug 2020, retrospective, Netherlands, peer-reviewed, 21 authors.
This PaperHCQAll
Outcomes of persons with coronavirus disease 2019 in hospitals with and without standard treatment with (hydroxy)chloroquine
Edgar Jg. Peters, Didier Collard, Sander Van Assen, Martijn Beudel, Marije K Bomers, Jacqueline Buijs, Lianne R De Haan, Wouter De Ruijter, Renée A Douma, Paul Wg. Elbers, Abraham Goorhuis, Niels C Gritters Van Den Oever, Lieve Ghh. Knarren, Hazra S Moeniralam, Remy Lm. Mostard, Marian Jr. Quanjel, Auke C Reidinga, Roos Renckens, Joop Pw. Van Den Bergh, Imro N Vlasveld, Jonne J Sikkens
Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.10.004
Objective: To compare survival of individuals with coronavirus disease 2019 (COVID-19) treated in hospitals that either did or did not routinely treat patients with hydroxychloroquine or chloroquine. Methods: We analysed data of COVID-19 patients treated in nine hospitals in the Netherlands. Inclusion dates ranged from 27 February to 15 May 2020, when the Dutch national guidelines no longer supported the use of (hydroxy)chloroquine. Seven hospitals routinely treated patients with (hydroxy)chloroquine, two hospitals did not. Primary outcome was 21-day all-cause mortality. We performed a survival analysis using log-rank test and Cox regression with adjustment for age, sex and covariates based on premorbid health, disease severity and the use of steroids for adult respiratory distress syndrome, including dexamethasone. Results: Among 1949 individuals, 21-day mortality was 21.5% in 1596 patients treated in hospitals that routinely prescribed (hydroxy)chloroquine, and 15.0% in 353 patients treated in hospitals that did not. In the adjusted Cox regression models this difference disappeared, with an adjusted hazard ratio of 1.09 (95% CI 0.81e1.47). When stratified by treatment actually received in individual patients, the use of (hydroxy)chloroquine was associated with an increased 21-day mortality (HR 1.58; 95% CI 1.24e2.02) in the full model.
Transparency declaration The authors declare that they have no conflicts of interest. Funding D. Collard is supported by a ZonMw grant (project no.: 10430022010002). Contribution of authors All authors have made substantial contributions to the following: the conception and design of the study, or acquisition of data, or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content; and final approval of the version to be submitted. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.cmi.2020.10.004.
References
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Late treatment
is less effective
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