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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
Sponsor:
Information provided by (Responsible Party):
Thomas Jefferson University

Tracking Information
First Submitted Date  ICMJE April 23, 2020
First Posted Date  ICMJE April 27, 2020
Last Update Posted Date May 5, 2020
Estimated Study Start Date  ICMJE May 2020
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2020)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2020)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacologic Ascorbic Acid as an Activator of Lymphocyte Signaling for COVID-19 Treatment
Official Title  ICMJE Pharmacologic Ascorbic Acid as an Activator of Lymphocyte Signaling for COVID-19 Treatment
Brief Summary 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.
Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE 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
Study Arms  ICMJE
  • Experimental: Treatment
    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.
    Intervention: Drug: Ascorbic Acid
  • No Intervention: Routine care
    These subject will follow routine care and their clinical courses will be recorded only.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: April 23, 2020)
66
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Michael W Foster, M.D. 6107160962 mxf314@jefferson.edu
Contact: Melissa McCarey 267 503-7417 melissa.mccarey@jefferson.edu
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04363216
Other Study ID Numbers  ICMJE JT#15681
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Thomas Jefferson University
Study Sponsor  ICMJE Thomas Jefferson University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Dagan Coppock, M.D. Thomas Jefferson University
Study Director: Daniel Monti, M.D. Thomas Jefferson University
PRS Account Thomas Jefferson University
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP