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All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ Mortality 50% Improvement Relative Risk Mortality (b) 80% Mortality (c) 50% Mortality (d) 70% Vitamin C  Zhang et al.  ICU PATIENTS  RCT Is very late treatment with vitamin C beneficial for COVID-19? RCT 56 patients in China (February - March 2020) Lower mortality with vitamin C (not stat. sig., p=0.2) c19early.org Zhang et al., Annals of Intensive Care, Aug 2020 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
Aug 2020  
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Vitamin C for COVID-19
6th treatment shown to reduce risk in September 2020
 
*, now known with p = 0.000000038 from 71 studies, recognized in 11 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,200+ studies for 70+ treatments. c19early.org
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 21 COVID-19 RCTs for vitamin C, which collectively show efficacy with p=0.0012.
This is the 2nd of 71 COVID-19 controlled studies for vitamin C, which collectively show efficacy with p=0.000000038 (1 in 26 million).
This study is excluded in the after exclusion results of meta analysis: very late stage, ICU patients.
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, study period 14 February, 2020 - 29 March, 2020, dosage 12000mg bid days 1-7.
This PaperVitamin CAll
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 ClinicalTrials.gov (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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' 'Arch Surg. 2000;135(3):326–31.', 'volume': '135', 'year': '2000'}, { 'DOI': '10.1186/s13054-018-2191-x', 'author': 'J Li', 'doi-asserted-by': 'publisher', 'first-page': '258', 'issue': '1', 'journal-title': 'Crit Care', 'key': '792_CR25', 'unstructured': 'Li J. Evidence is stronger than you think: a meta-analysis of vitamin C ' 'use in patients with sepsis. Crit Care. 2018;22(1):258.', 'volume': '22', 'year': '2018'}, { 'DOI': '10.1007/s40256-018-0274-3', 'author': 'Y Xu', 'doi-asserted-by': 'publisher', 'first-page': '373', 'issue': '5', 'journal-title': 'Am J Cardiovasc Drugs', 'key': '792_CR26', 'unstructured': 'Xu Y, Zheng X, Liang B, Gao J, Gu Z. Vitamins for prevention of ' 'contrast-induced acute kidney injury: a systematic review and trial ' 'sequential analysis. 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Intensive Care Med. 2020;46(5):846–8.', 'volume': '46', 'year': '2020'}, { 'DOI': '10.1016/j.jaut.2020.102452', 'author': 'B Liu', 'doi-asserted-by': 'publisher', 'first-page': '102452', 'journal-title': 'J Autoimmun', 'key': '792_CR38', 'unstructured': 'Liu B, Li M, Zhou Z, Guan X, Xiang Y. Can we use interleukin-6 (IL-6) ' 'blockade for coronavirus disease (COVID-19)-induced cytokine release ' 'syndrome (CRS). J Autoimmun. 2020;111:102452.', 'volume': '111', 'year': '2020'}, { 'DOI': '10.2217/imt-2016-0020', 'author': 'T Tanaka', 'doi-asserted-by': 'publisher', 'first-page': '959', 'issue': '8', 'journal-title': 'Immunotherapy', 'key': '792_CR39', 'unstructured': 'Tanaka T, Narazaki M, Kishimoto T. Immunotherapeutic implications of ' 'IL-6 blockade for cytokine storm. Immunotherapy. 2016;8(8):959–70.', 'volume': '8', 'year': '2016'}, { 'DOI': '10.1016/S0140-6736(03)15326-3', 'author': 'N Pathan', 'doi-asserted-by': 'publisher', 'first-page': '203', 'issue': '9404', 'journal-title': 'Lancet', 'key': '792_CR40', 'unstructured': 'Pathan N, Hemingway CA, Alizadeh AA, Stephens AC, Boldrick JC, Oragui ' 'EE, McCabe C, Welch SB, Whitney A, O’Gara P, et al. Role of interleukin ' '6 in myocardial dysfunction of meningococcal septic shock. Lancet. ' '2004;363(9404):203–9.', 'volume': '363', 'year': '2004'}, { 'DOI': '10.1073/pnas.2005615117', 'doi-asserted-by': 'crossref', 'key': '792_CR41', 'unstructured': 'Xu X, Han M, Li T, Sun W, Wang D, Fu B, Zhou Y, Zheng X, Yang Y, Li X et ' 'al: Effective treatment of severe COVID-19 patients with tocilizumab. ' 'Proc Natl Acad Sci U S A 2020.'}, { 'DOI': '10.1016/j.cyto.2004.02.004', 'author': 'C Hartel', 'doi-asserted-by': 'publisher', 'first-page': '101', 'issue': '4–5', 'journal-title': 'Cytokine', 'key': '792_CR42', 'unstructured': 'Hartel C, Strunk T, Bucsky P, Schultz C. Effects of vitamin C on ' 'intracytoplasmic cytokine production in human whole blood monocytes and ' 'lymphocytes. Cytokine. 2004;27(4–5):101–6.', 'volume': '27', 'year': '2004'}], 'reference-count': 42, 'references-count': 42, 'relation': {}, 'resource': { 'primary': { 'URL': 'https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00792-3'}}, 'score': 1, 'short-title': [], 'source': 'Crossref', 'subject': ['Critical Care and Intensive Care Medicine'], 'subtitle': [], 'title': 'Pilot trial of high-dose vitamin C in critically ill COVID-19 patients', 'type': 'journal-article', 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'volume': '11'}
Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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