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Administration of Intravenous Vitamin C in Novel Coronavirus Infection (COVID-19) and Decreased Oxygenation (AVoCaDO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04357782
Recruitment Status : Completed
First Posted : April 22, 2020
Last Update Posted : December 23, 2020
Sponsor:
Collaborator:
McGuire Research Institute
Information provided by (Responsible Party):
Brian C. Davis, MD, Hunter Holmes Mcguire Veteran Affairs Medical Center

Tracking Information
First Submitted Date  ICMJE April 17, 2020
First Posted Date  ICMJE April 22, 2020
Last Update Posted Date December 23, 2020
Actual Study Start Date  ICMJE April 16, 2020
Actual Primary Completion Date October 13, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 20, 2020)
  • Incidence of adverse events [ Time Frame: Days 1-4 ]
    Occurrence of adverse events during study drug infusion
  • Incidence of serious adverse reactions [ Time Frame: Days 1-4 ]
    Occurrence of serious adverse events during study drug infusion
  • Incidence of adverse reactions [ Time Frame: Days 1-4 ]
    Occurrence of adverse reactions during study drug infusion
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2020)
  • Ventilator-free days [ Time Frame: Days 1-28 ]
    Documented days free off mechanical ventilation the first 28 days post enrollment
  • ICU-free days [ Time Frame: Days 1-28 ]
    Documented days free of ICU admission the first 28 days post enrollment
  • Hospital-free days [ Time Frame: Days 1-28 ]
    Documented days free of hospital admission the first 28 days post enrollment
  • All-cause mortality [ Time Frame: Days 1-28 ]
    Incidence of mortality at 28 days by all causes
  • Change in S/F ratio during HDIVC infusion [ Time Frame: Days 1-4 ]
    SpO2 (% peripheral oxygenation saturation) will be divided by fraction of inspired oxygen (FiO2) at start of study infusion and compared with S/F ratio at end of study infusion
  • C-reactive protein (CRP) [ Time Frame: Days 1-4 ]
    The difference in serum CRP during HDIVC infusion reported in mg/dL
  • Lactate dehydrogenase (LDH) [ Time Frame: Days 1-4 ]
    The difference in LDH during HDIVC infusion will be reported in IU/L
  • D-dimer [ Time Frame: Days 1-4 ]
    The difference in D-dimer during HDIVC infusion will be reported in ug/mL
  • Lymphocyte count [ Time Frame: Days 1-4 ]
    The difference in lymphocyte count during HDIVC infusion will be reported in 10e3/uL
  • Neutrophil to Lymphocyte ratio (NLR) [ Time Frame: Days 1-4 ]
    The NLR will be calculated by dividing the absolute neutrophil count (10e3/uL) over the absolute lymphocyte count (10e3/uL) and ratio compared with Day 1 versus Day 4
  • Serum Ferritin [ Time Frame: Days 1-4 ]
    The difference in serum ferritin will be calculated from the start of HDIVC infusion to day 4 and reported as ng/mL
Original Secondary Outcome Measures  ICMJE
 (submitted: April 20, 2020)
  • Ventilator-free days [ Time Frame: Days 1-28 ]
    Documented days free off mechanical ventilation the first 28 days post enrollment
  • ICU-free days [ Time Frame: Days 1-28 ]
    Documented days free of ICU admission the first 28 days post enrollment
  • Hospital-free days [ Time Frame: Days 1-28 ]
    Documented days free of hospital admission the first 28 days post enrollment
  • All-cause mortality [ Time Frame: Days 1-28 ]
    Incidence of mortality at 28 days by all causes
  • Change in S/F ratio during HDIVC infusion [ Time Frame: Days 1-4 ]
    SpO2 (% peripheral oxygenation saturation) will be divided by fraction of inspired oxygen (FiO2) at start of study infusion and compared with S/F ratio at end of study infusion
  • C-reactive protein (CRP) [ Time Frame: Days 1-7 ]
    The difference in serum CRP from start of HDIVC infusion to day 7 will be reported in mg/dL
  • Lactate dehydrogenase (LDH) [ Time Frame: Days 1-7 ]
    The difference in LDH from start of HDIVC infusion to day 7 will be reported in IU/L
  • D-dimer [ Time Frame: Days 1-7 ]
    The difference in D-dimer from start of HDIVC infusion to day 7 will be reported in ug/mL
  • Lymphocyte count [ Time Frame: Days 1-7 ]
    The difference in lymphocyte count from start of HDIVC infusion to day 7 will be reported in 10e3/uL
  • Neutrophil to Lymphocyte ratio (NLR) [ Time Frame: Days 1-7 ]
    The NLR will be calculated by dividing the absolute neutrophil count (10e3/uL) over the absolute lymphocyte count (10e3/uL) and ratio compared with Day 1 versus Day 7
  • Serum Ferritin [ Time Frame: Days 1-7 ]
    The difference in serum ferritin will be calculated from the start of HDIVC infusion to day 7 and reported as ng/mL
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Administration of Intravenous Vitamin C in Novel Coronavirus Infection (COVID-19) and Decreased Oxygenation
Official Title  ICMJE Administration of Intravenous Vitamin C in Novel Coronavirus Infection and Decreased Oxygenation (AVoCaDO): A Phase I/II Safety, Tolerability, and Efficacy Clinical Trial
Brief 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, CRP, 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • COVID-19
  • Hypoxia
Intervention  ICMJE 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
Study Arms  ICMJE
  • Active Comparator: Mild hypoxemia
    S/F ratio >250 prior to Vitamin C infusion
    Intervention: Drug: L-ascorbic acid
  • Active Comparator: Severe Hypoxemia
    S/F ratio ≤250 prior to Vitamin C infusion
    Intervention: Drug: L-ascorbic acid
Publications *

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: April 20, 2020)
20
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 13, 2020
Actual Primary Completion Date October 13, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04357782
Other Study ID Numbers  ICMJE Davis 001
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Brian C. Davis, MD, Hunter Holmes Mcguire Veteran Affairs Medical Center
Study Sponsor  ICMJE Hunter Holmes Mcguire Veteran Affairs Medical Center
Collaborators  ICMJE McGuire Research Institute
Investigators  ICMJE
Principal Investigator: Brian C Davis, MD Staff Physician, GI Division
PRS Account Hunter Holmes Mcguire Veteran Affairs Medical Center
Verification Date December 2020

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