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.
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.
Drug: L-ascorbic acid
50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
Other Name: Vitamin C, Ascor
Inclusion Criteria:
- Hospitalized with diagnosis of COVID-19 based on positive reverse transcriptase
polymerase chain reaction (RT-PCR) SARS-CoV-2 of nasal, oropharyngeal, or
bronchoalveolar (BAL) specimen
- Mild deoxygenation defined as S/F ratio decreased by 25% from baseline on admission,
or SpO2 <95% breathing ambient air on admission
- Non-childbearing potential or childbearing potential with a negative pregnancy test at
screening, and using a reliable method of contraception (i.e., abstinence, hormonal
contraception, intrauterine device (IUD), or vasectomized partner)
Exclusion Criteria:
- Known allergy to Vitamin C
- Inability to obtain consent from patient or next of kin
- Chronic kidney disease, stage IV or above (eGFR <30)
- Presence of diabetic ketoacidosis, use of insulin infusion, or frequent need for
point-of-care glucose monitoring (>6 times/24 hour period) as determined by treating
physician
- History of glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Active or history of kidney stone within past 12 months
- Pregnancy
- Enrolled in another COVID-19 clinical trial that does not allow concomitant study
drugs
Hunter Holmes Mcguire Veteran Affairs Medical Center
Richmond, Virginia, United States
Brian C Davis, MD, Principal Investigator
Staff Physician, GI Division