There are currently no approved therapies for patients with coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infusion of ascorbic acid (vitamin C) has been shown to increase activity of lymphocytes, which are a crucial component of the body's defense against viral disease progression and adaptive immunity. Ascorbic acid infusion has been shown to be a safe treatment for patients suffering from sepsis and certain types of cancer. This study is designed to evaluate the safety and efficacy of ascorbic acid in the form of sequential I.V. infusions (Ascor®) for patients with suspected COVID-19 who are unlikely to require mechanical ventilation within 24 hours of study intervention.
Ascorbic acid [AA] (vitamin C) is an essential nutrient that, in addition to aiding tissue
repair, also functions as an enzyme co-factor, an antioxidant, and a key component in
lymphocyte development and function. Lymphocytes are responsible for adaptive immunity, the
immune response following vaccination, in addition to playing a vital role in protection
against viral disease progression. Both sepsis and aberrant lymphocyte activation have been
associated with severe AA deficiency. We hypothesize that the administration of increasing
concentrations of pharmacologic AA promotes lymphocyte activation and signaling in newly
admitted, non-ventilator dependent COVID-19 patients via hydrogen peroxide generation and/or
DNA de-methylation, and that this will lead to improved clinical outcomes.
This is a single-center, prospective, randomized, open-label, phase II clinical trial
designed to assess the efficacy, tolerability, and safety of pharmacologic AA administration
in hospitalized patients newly-diagnosed with COVID-19 who will likely not require mechanical
ventilation within 24 hours of study intervention. All subjects enrolled will be pending
inpatient admission or already admitted as they will require supplemental oxygen. Within 12
hours of admission to the E.D. or medical/surgical floor (rapid screens to determine
eligibility must be completed within this time), patients will receive escalating
pharmacologic AA over 2 hours once daily for 3 escalating doses, then continued on the
highest dose for a total of 6 infusions.
Subjects will be randomized 2:1, with 66 subjects receiving AA treatments and 22 subjects
receiving routine clinical care. The open-label design allows investigators to evaluate the
safety and clinical progress in real-time. Any subject randomized to AA treatment who is
upgraded to ICU-level care, requires high-flow O2 supplementation, or is intubated, will no
longer receive AA infusions in order to maximize patient safety during this study. Given the
robust safety data on the treatment, a phase II design was chosen with an interim safety
analysis after 21 patients. Randomization will be stratified according to high vs. low risk
of complications. Patients will be considered to be high risk if they have any of the
following characteristics: age>60, hypertension, structural lung disease, cardiovascular
disease, diabetes, immunocompromising conditions or meds (such as immunosuppressing meds in
transplant patients).
Drug: Ascorbic Acid
Ascor® ascorbic acid 2-hour infusion daily (for 6 days), escalating dose (0.3g/kg, 0.6g/kg, 0.9g/kg).
Other Name: Vitamin C
Inclusion Criteria:
1. Male or non-pregnant female > 18 years of age at the time of consent
2. ConfirmedSARS-CoV-2 infection
3. Disease severity necessitating hospitalization
4. Currently taking supplemental oxygen
5. No anticipated need (within 24 hours) for mechanical ventilation, defined as:
1. Positive clinical response to oxygen supplementation with improvement in hypoxia
or
2. Hypoxia improvement with bronchospasm therapy if bronchospasm present
Exclusion Criteria
1. eGFR < 50
2. Known Glucose-6-phosphate dehydrogenase (G6PD) deficiency
3. Anticipated need for mechanical ventilation within 24 hours
4. Pregnant or breastfeeding
5. Requires home oxygen for any reason
Michael W Foster, M.D.
6107160962
mxf314@jefferson.edu
Melissa McCarey
267 503-7417
melissa.mccarey@jefferson.edu