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0 0.5 1 1.5 2+ Mortality 50% Improvement Relative Risk Mortality (b) 80% Mortality (c) 50% Mortality (d) 70% Zhang et al. Vitamin C for COVID-19 RCT ICU PATIENTS Is very late treatment with vitamin C beneficial for COVID-19? RCT 56 patients in China Lower mortality with vitamin C (not stat. sig., p=0.2) Zhang et al., Annals of Intensive Care, doi:10.1186/s13613-020-00792-3 Favors vitamin C Favors control
Pilot Trial of High-dose vitamin C in critically ill COVID-19 patients (preprint 8/10/2020)
Zhang et al., Annals of Intensive Care, doi:10.1186/s13613-020-00792-3
Zhang et al., Pilot Trial of High-dose vitamin C in critically ill COVID-19 patients (preprint 8/10/2020), Annals of Intensive Care, doi:10.1186/s13613-020-00792-3
Aug 2020   Source   PDF  
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Small RCT for high dose vitamin C for ICU patients showing reduced (but not statistically significant) mortality. Dosage was 12g of vitamin C/50ml every 12 hours for 7 days at a rate of 12ml/hour.
This is the 1st of 15 COVID-19 RCTs for vitamin C, which collectively show efficacy with p=0.00013.
This is the 2nd of 61 COVID-19 controlled studies for vitamin C, which collectively show efficacy with p=0.00000098.
risk of death, 50.0% lower, RR 0.50, p = 0.20, treatment 6 of 27 (22.2%), control 11 of 29 (37.9%), NNT 6.4, adjusted per study, ICU mortality.
risk of death, 80.0% lower, RR 0.20, p = 0.04, treatment 5 of 27 (18.5%), control 11 of 29 (37.9%), NNT 5.2, adjusted per study, ICU mortality for SOFA>=3.
risk of death, 50.0% lower, RR 0.50, p = 0.31, treatment 6 of 27 (22.2%), control 10 of 29 (34.5%), NNT 8.2, adjusted per study, 28 day mortality.
risk of death, 70.0% lower, RR 0.30, p = 0.07, treatment 5 of 27 (18.5%), control 10 of 29 (34.5%), NNT 6.3, adjusted per study, 28 day mortality for SOFA>=3.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Zhang et al., 10 Aug 2020, Randomized Controlled Trial, China, peer-reviewed, 11 authors.
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Pilot trial of high-dose vitamin C in critically ill COVID-19 patients
Jing Zhang, Xin Rao, Yiming Li, Yuan Zhu, Fang Liu, Guangling Guo, Guoshi Luo, Zhongji Meng, Daniel De Backer, Hui Xiang, Zhiyong Peng
Annals of Intensive Care, doi:10.1186/s13613-020-00792-3
Background: Few specific medications have been proven effective for the treatment of patients with severe coronavirus disease 2019 . Here, we tested whether high-dose vitamin C infusion was effective for severe COVID-19. Methods: This randomized, controlled, clinical trial was performed at 3 hospitals in Hubei, China. Patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the ICU were randomly assigned in as 1:1 ratio to either the high-dose intravenous vitamin C (HDIVC) or the placebo. HDIVC group received 12 g of vitamin C/50 ml every 12 h for 7 days at a rate of 12 ml/hour, and the placebo group received bacteriostatic water for injection in the same way within 48 h of arrival to ICU. The primary outcome was invasive mechanical ventilation-free days in 28 days (IMVFD28). Secondary outcomes were 28-day mortality, organ failure (Sequential Organ Failure Assessment (SOFA) score), and inflammation progression (interleukin-6). Results: Only 56 critical COVID-19 patients were ultimately recruited due to the early control of the outbreak. There was no difference in IMVFD28 between two groups (26.0 [9.0-28.0] in HDIVC vs 22.0 [8.50-28.0] in control, p = 0.57). HDIVC failed to reduce 28-day mortality (P = 0.27). During the 7-day treatment period, patients in the HDIVC group had a steady rise in the PaO 2 /FiO 2 (day 7: 229 vs. 151 mmHg, 95% CI 33 to 122, P = 0.01), which was not observed in the control group. IL-6 in the HDIVC group was lower than that in the control group (19.42 vs. 158.00; 95% CI -301.72 to -29.79; P = 0.04) on day 7. Conclusion: This pilot trial showed that HDIVC failed to improve IMVFD28, but might show a potential signal of benefit in oxygenation for critically ill patients with COVID-19 improving PaO2/FiO2 even though.
Authors' contributions Concept and design: JZ, XR, YL. Acquisition, analysis, or interpretation of data: JZ, XR, YL, HX, GG, GL, ZM. Drafting of the manuscript: JZ, XR, YL, DB, ZP. Critical revision of the manuscript for important intellectual content: JZ, XR, YL, DB, ZP. Statistical analysis: JZ, YZ, FL. Obtained funding: HX, ZP. Administrative, technical, or material support: HX, XR, ZP. Supervision: HX, DB, ZP. All authors read and approved the final manuscript. Ethics approval and consent to participate This study is a multicenter, randomized trial, which was approved by the ethic committee of Zhongnan Hospital of Wuhan University (#2020001). It was registered on the website of (ID: NCT04264533) before patient recruitment. Informed consents were obtained from the patients or family members. Competing interests The authors declare no competing interests. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Late treatment
is less effective
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