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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 : Active, not recruiting
First Posted : April 22, 2020
Last Update Posted : September 18, 2020
Sponsor:
Collaborator:
McGuire Research Institute
Information provided by (Responsible Party):
Brian C. Davis, MD, Hunter Holmes Mcguire Veteran Affairs Medical Center

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.


Condition or disease Intervention/treatment Phase
COVID-19 Hypoxia Drug: L-ascorbic acid Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
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
Official Title: Administration of Intravenous Vitamin C in Novel Coronavirus Infection and Decreased Oxygenation (AVoCaDO): A Phase I/II Safety, Tolerability, and Efficacy Clinical Trial
Actual Study Start Date : April 16, 2020
Estimated Primary Completion Date : September 18, 2020
Estimated Study Completion Date : October 15, 2020


Arm Intervention/treatment
Active Comparator: Mild hypoxemia
S/F ratio >250 prior to Vitamin C infusion
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

Active Comparator: Severe Hypoxemia
S/F ratio ≤250 prior to Vitamin C infusion
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




Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Days 1-4 ]
    Occurrence of adverse events during study drug infusion

  2. Incidence of serious adverse reactions [ Time Frame: Days 1-4 ]
    Occurrence of serious adverse events during study drug infusion

  3. Incidence of adverse reactions [ Time Frame: Days 1-4 ]
    Occurrence of adverse reactions during study drug infusion


Secondary Outcome Measures :
  1. Ventilator-free days [ Time Frame: Days 1-28 ]
    Documented days free off mechanical ventilation the first 28 days post enrollment

  2. ICU-free days [ Time Frame: Days 1-28 ]
    Documented days free of ICU admission the first 28 days post enrollment

  3. Hospital-free days [ Time Frame: Days 1-28 ]
    Documented days free of hospital admission the first 28 days post enrollment

  4. All-cause mortality [ Time Frame: Days 1-28 ]
    Incidence of mortality at 28 days by all causes

  5. 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

  6. C-reactive protein (CRP) [ Time Frame: Days 1-4 ]
    The difference in serum CRP during HDIVC infusion reported in mg/dL

  7. Lactate dehydrogenase (LDH) [ Time Frame: Days 1-4 ]
    The difference in LDH during HDIVC infusion will be reported in IU/L

  8. D-dimer [ Time Frame: Days 1-4 ]
    The difference in D-dimer during HDIVC infusion will be reported in ug/mL

  9. Lymphocyte count [ Time Frame: Days 1-4 ]
    The difference in lymphocyte count during HDIVC infusion will be reported in 10e3/uL

  10. 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

  11. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

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): NCT04357782


Locations
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United States, Virginia
Hunter Holmes Mcguire Veteran Affairs Medical Center
Richmond, Virginia, United States, 23249
Sponsors and Collaborators
Hunter Holmes Mcguire Veteran Affairs Medical Center
McGuire Research Institute
Investigators
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Principal Investigator: Brian C Davis, MD Staff Physician, GI Division
Publications:

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Responsible Party: Brian C. Davis, MD, Staff Physician, Hunter Holmes Mcguire Veteran Affairs Medical Center
ClinicalTrials.gov Identifier: NCT04357782    
Other Study ID Numbers: Davis 001
First Posted: April 22, 2020    Key Record Dates
Last Update Posted: September 18, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Brian C. Davis, MD, Hunter Holmes Mcguire Veteran Affairs Medical Center:
Vitamin C
Ascorbic Acid
Hypoxia
Sepsis
Acute Lung Injury
Acute Respiratory Distress Syndrome
SARS-CoV-2
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Hypoxia
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Signs and Symptoms, Respiratory
Respiratory Tract Infections
Respiratory Tract Diseases
Ascorbic Acid
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents