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Intravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trial
  1. Fang Liu,
  2. Yuan Zhu,
  3. Jing Zhang,
  4. Yiming Li,
  5. Zhiyong Peng
  1. Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
  1. Correspondence to Dr Zhiyong Peng; Pengzy5{at}


Introduction The rapid worldwide spread of COVID-19 has caused a global health crisis. To date, symptomatic supportive care has been the most common treatment. It has been reported that the mechanism of COVID-19 is related to cytokine storms and subsequent immunogenic damage, especially damage to the endothelium and alveolar membrane. Vitamin C (VC), also known as L-ascorbic acid, has been shown to have antimicrobial and immunomodulatory properties. A high dose of intravenous VC (HIVC) was proven to block several key components of cytokine storms, and HIVC showed safety and varying degrees of efficacy in clinical trials conducted on patients with bacterial-induced sepsis and acute respiratory distress syndrome (ARDS). Therefore, we hypothesise that HIVC could be added to the treatment of ARDS and multiorgan dysfunction related to COVID-19.

Methods and analysis The investigators designed a multicentre prospective randomised placebo-controlled trial that is planned to recruit 308 adults diagnosed with COVID-19 and transferred into the intensive care unit. Participants will randomly receive HIVC diluted in sterile water or placebo for 7 days once enrolled. Patients with a history of VC allergy, end-stage pulmonary disease, advanced malignancy or glucose-6-phosphate dehydrogenase deficiency will be excluded. The primary outcome is ventilation-free days within 28 observational days. This is one of the first clinical trials applying HIVC to treat COVID-19, and it will provide credible efficacy and safety data. We predict that HIVC could suppress cytokine storms caused by COVID-19, help improve pulmonary function and reduce the risk of ARDS of COVID-19.

Ethics and dissemination The study protocol was approved by the Ethics Committee of Zhongnan Hospital of Wuhan University (identifiers: Clinical Ethical Approval No. 2020001). Findings of the trial will be disseminated through peer-reviewed journals and scientific conferences.

Trial registration number NCT04264533.

  • infectious diseases
  • adult intensive & critical care
  • clinical trials
  • respiratory infections
  • adult intensive & critical care

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  • FL and YZ contributed equally.

  • Contributors FL, YZ, JZ, YL, and ZP designed this study; FL, YZ, and JZ designed the statistical analysis plan; JZ and YL wrote the bid for the research project and obtained permission from the ethics committees; FL, YZ, JZ, and YL carried out this trial; FL and YZ drafted this manuscript; ZP, YL, and JZ carefully reviewed the manuscript; and all authors read and approved the final manuscript.

  • Funding This work was supported by the Science and Technology Department of Hubei Province (grant number: 2020FCA024) and the Special Project for Significant New Drug Research and Development in the Major National Science and Technology Projects of China (grant number: 2020ZX09201007). The foundations have reviewed and approved this project. The primary investigator is supposed to report the progress of this trial to the departments regularly.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval This study follows the principles of the Helsinki Declaration 2013. The entire protocol was reviewed and approved by the Ethics Committee of Zhongnan Hospital of Wuhan University (identifier: Clinical Ethical Approval No. 2020001). Zhongnan Hospital of Wuhan University also took charge of the management of Leishenshan Hospital of Wuhan City, including affairs of clinical trials, so the above ethical approval document is also applicable to Leishenshan Hospital. Written informed consent will be obtained from all participants who will be informed about the purpose, intervention and possible risks/benefits of the study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Author note The trial was registered on (identifier: NCT04264533) on 4 February 2020. Of note, this manuscript is a revised version of the protocol that was reviewed and approved on 19 February 2020. The first version was approved on 31 January 2020. Compared with the first version, which was registered on, the sample size and secondary outcomes of this version have been revised, as there was insufficient information about COVID-19 at the early stage, and we have learned more about COVID-19 over time.