Administration of Intravenous Vitamin C in Novel Coronavirus Infection (COVID-19) and Decreased Oxygenation
Condition: COVID-19; Hypoxia
MeSH terms: COVID-19; Coronavirus Infections; Hypoxia
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Previous research has shown that high dose intravenous vitamin C (HDIVC) may benefit patients
      with sepsis, acute lung injury (ALI), and the acute respiratory distress syndrome (ARDS).
      However, it is not known if early administration of HDIVC could prevent progression to ARDS.

      We hypothesize that HDIVC is safe and tolerable in Coronavirus disease 2019 (COVID-19)
      subjects given early or late in the disease course and may reduce the risk of respiratory
      failure requiring mechanical ventilation and development of ARDS along with reductions in
      supplemental oxygen demand and inflammatory markers.
    

Detailed description: 
      The purpose of this study is to assess the safety, tolerability, potential efficacy of high
      dose intravenous vitamin C (HDIVC) therapy for patients with COVID-19 and decreased
      oxygenation. COVID-19 is a rapidly evolving pandemic with numerous prediction models
      suggesting potential shortages in ventilators, ICU beds, and high rates of hospital
      mortality. Case-series suggest sepsis and the acute respiratory distress syndrome (ARDS) are
      driving hospitalizations, morbidity (ICU beds, ventilator use, organ failures), and
      mortality. A therapy is urgently needed to be given early in the disease course in order to
      attenuate the infectious and inflammatory process, reduce risk of intubation, and reduce
      progression of organ failure and ARDS. By administering HDIVC at the first objective sign of
      worsening oxygenation, documented by change in peripheral capillary oxygen saturation (SpO2)
      to fraction of inspired oxygen (FIO2) ratio (S/F) or decreased SpO2 at baseline (mild hypoxia
      group), HDIVC may reduce the inflammatory process and development of respiratory failure
      requiring intubation. We will also enroll patients already in respiratory failure on
      ventilators (severe hypoxia group) and document safety and tolerability in both cohorts. By
      calculating ventilator and ICU-free days, we can potentially signal clinically relevant
      endpoints that could be used in larger trials needed to answer a crucial therapeutic
      question-can early administration of HDIVC in COVID-19 lead to faster recovery or improve
      outcomes? Moreover, we will document change in inflammatory markers that are elevated in
      COVID-19 (d-dimer, C reactive protein (CRP), lactate dehydrogenase (LDH), liver enzymes, and
      ferritin) to develop a mechanistic understanding and risk stratification of response to HDIVC
      infusion. Ultimately, if HDIVC is deemed safe and tolerable in hospitalized COVID-19
      subjects, a larger clinical trial will be indicated. AVoCaDO will produce safety and
      tolerability data to test HDIVC in a multi-center, rapid, randomized, placebo-controlled
      trial of subjects with COVID-19.
    

Intervention name(s): L-ascorbic acid
Intervention type(s): Drug
Intervention description(s): 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
Other intervention name(s): Vitamin C, Ascor
Intervention MeSH terms: Ascorbic Acid
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Intervention model description: Parallel: Participants are assigned to one of two or more groups in parallel for the duration of the study
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Vitamin C; Ascorbic Acid; Hypoxia; Sepsis; Acute Lung Injury; Acute Respiratory Distress Syndrome; Severe acute respiratory syndrome (SARS)- Coronavirus (CoV)-2