Pharmacologic Ascorbic Acid as an Activator of Lymphocyte Signaling for COVID-19 Treatment
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|ClinicalTrials.gov Identifier: NCT04363216|
Recruitment Status : Not yet recruiting
First Posted : April 27, 2020
Last Update Posted : May 5, 2020
|Condition or disease||Intervention/treatment||Phase|
|COVID-19||Drug: Ascorbic Acid||Phase 2|
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).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||66 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pharmacologic Ascorbic Acid as an Activator of Lymphocyte Signaling for COVID-19 Treatment|
|Estimated Study Start Date :||May 2020|
|Estimated Primary Completion Date :||May 2021|
|Estimated Study Completion Date :||May 2021|
Ascorbic acid solution (Ascor®, McGuff Pharmaceuticals, Ltd.) will be added to each liter of sterile wate,r plus 1 g/L magnesium chloride to reduce burning sensation, and given parenterally over a 2-hour period. On the day of enrollment (Day 0), 0.3 g/kg will be given; Day 1 - 0.6 g/kg; Day 2 - 0.9 g/kg; Day 3 - 0.9 g/kg; Day 4 - 0.9 g/kg; Day 5 - 0.9 g/kg. After the first dose, each subsequent dose will be given 24 +/- 4 hours following the previous dose.
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
No Intervention: Routine care
These subject will follow routine care and their clinical courses will be recorded only.
- Clinical Improvement [ Time Frame: 72 hours ]• Clinical improvement at 72 hours of treatment, defined as a 50% reduction in the highest flow rate of oxygen during the 72 hour period, a 50% reduction in the most frequent use of bronchodilators within a 12-hour window within the 72-hour period, or hospital discharge (whichever comes first).
- Patient status upgraded to ICU level [Clinical decline] [ Time Frame: 36 hours ]Subject is upgraded to ICU-level care
- Oxygen supplementation [ Time Frame: up to 1 year ]Overall rate of oxygen supplementation in L/min
- Days with fever [ Time Frame: up to 1 year ]Number of days during hospitalization where a fever (>100.4°F) is reached at least once
- Days to discharge [ Time Frame: up to 1 year ]Number of days from initial treatment to hospital discharge
- SAEs [ Time Frame: up to 1 year ]Serious adverse events specific to treatment
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04363216
|Contact: Michael W Foster, M.D.||firstname.lastname@example.org|
|Contact: Melissa McCarey||267 email@example.com|
|Principal Investigator:||Dagan Coppock, M.D.||Thomas Jefferson University|
|Study Director:||Daniel Monti, M.D.||Thomas Jefferson University|