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

NCT04357782 | Completed Phase 1 Results FDA Drug

• 1 other identifier: Davis 001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID-19; Hypoxia

Keywords

Vitamin C; Ascorbic Acid; Hypoxia; Sepsis; Acute Lung Injury; Acute Respiratory Distress Syndrome; Severe acute respiratory syndrome (SARS)- Coronavirus (CoV)-2

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Adverse Events Related to High Dose Intravenous Vitamin C (HDIVC)

  Occurrence of adverse events during study drug infusion as defined in the Ascor package insert ie acute kidney injury (increase in serum creatinine 3x baseline prior to initial HDIVC dose, hemolysis, iatrogenic hypoglycemia, pain at swelling site of infusion, crystalluria on urinalysis (UA) after last HDIVC dose

  Days 1-4

• Number of Participants With Serious Adverse Reactions

  Number of participants with serious adverse events during study drug infusion

  Days 1-4

• Number of Participants With Adverse Reactions

  Number of participants with adverse reactions during study drug infusion

  Days 1-4

Secondary Outcomes (11)

• Ventilator-free Days

  Days 1-28

• Intensive Care Unit (ICU)-Free Days

  Days 1-28

• Hospital-free Days

  Days 1-28

• All-cause Mortality

  Days 1-28

• Change in S/F Ratio During High Dose Intravenous Vitamin C (HDIVC)

  Days 1-4

Study Arms (2)

Mild hypoxemia

ACTIVE COMPARATOR

S/F ratio \>250 prior to Vitamin C infusion

Drug: L-ascorbic acid

Severe Hypoxemia

ACTIVE COMPARATOR

S/F ratio ≤250 prior to Vitamin C infusion

Drug: L-ascorbic acid

Interventions

L-ascorbic acid DRUG

50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)

Also known as: Vitamin C, Ascor

Mild hypoxemia; Severe Hypoxemia

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Hunter Holmes Mcguire Veteran Affairs Medical Center: lead
• McGuire Research Institute: collaborator

Study Sites (1)

Hunter Holmes Mcguire Veteran Affairs Medical Center

Richmond, Virginia, 23249, United States

Location

Related Publications (7)

• Fowler AA 3rd, Truwit JD, Hite RD, Morris PE, DeWilde C, Priday A, Fisher B, Thacker LR 2nd, Natarajan R, Brophy DF, Sculthorpe R, Nanchal R, Syed A, Sturgill J, Martin GS, Sevransky J, Kashiouris M, Hamman S, Egan KF, Hastings A, Spencer W, Tench S, Mehkri O, Bindas J, Duggal A, Graf J, Zellner S, Yanny L, McPolin C, Hollrith T, Kramer D, Ojielo C, Damm T, Cassity E, Wieliczko A, Halquist M. Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial. JAMA. 2019 Oct 1;322(13):1261-1270. doi: 10.1001/jama.2019.11825.

  PMID: 31573637 BACKGROUND

• Fowler AA 3rd, Fisher BJ, Kashiouris MG. Vitamin C for Sepsis and Acute Respiratory Failure-Reply. JAMA. 2020 Feb 25;323(8):792-793. doi: 10.1001/jama.2019.21987. No abstract available.

  PMID: 32096845 BACKGROUND

• Sindel A, Taylor T, Chesney A, Clark W, Fowler AA 3rd, Toor AA. Hematopoietic stem cell mobilization following PD-1 blockade: Cytokine release syndrome after transplantation managed with ascorbic acid. Eur J Haematol. 2019 Aug;103(2):134-136. doi: 10.1111/ejh.13248. Epub 2019 Jun 7.

  PMID: 31140644 BACKGROUND

• Fowler AA 3rd, Syed AA, Knowlson S, Sculthorpe R, Farthing D, DeWilde C, Farthing CA, Larus TL, Martin E, Brophy DF, Gupta S; Medical Respiratory Intensive Care Unit Nursing; Fisher BJ, Natarajan R. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014 Jan 31;12:32. doi: 10.1186/1479-5876-12-32.

  PMID: 24484547 BACKGROUND

• Fisher BJ, Kraskauskas D, Martin EJ, Farkas D, Puri P, Massey HD, Idowu MO, Brophy DF, Voelkel NF, Fowler AA 3rd, Natarajan R. Attenuation of sepsis-induced organ injury in mice by vitamin C. JPEN J Parenter Enteral Nutr. 2014 Sep;38(7):825-39. doi: 10.1177/0148607113497760. Epub 2013 Aug 5.

  PMID: 23917525 BACKGROUND

• Fowler Iii AA, Kim C, Lepler L, Malhotra R, Debesa O, Natarajan R, Fisher BJ, Syed A, DeWilde C, Priday A, Kasirajan V. Intravenous vitamin C as adjunctive therapy for enterovirus/rhinovirus induced acute respiratory distress syndrome. World J Crit Care Med. 2017 Feb 4;6(1):85-90. doi: 10.5492/wjccm.v6.i1.85. eCollection 2017 Feb 4.

  PMID: 28224112 BACKGROUND

• Kashiouris MG, L'Heureux M, Cable CA, Fisher BJ, Leichtle SW, Fowler AA. The Emerging Role of Vitamin C as a Treatment for Sepsis. Nutrients. 2020 Jan 22;12(2):292. doi: 10.3390/nu12020292.

  PMID: 31978969 BACKGROUND

MeSH Terms

Conditions

COVID-19; Hypoxia; Sepsis; Acute Lung Injury; Respiratory Distress Syndrome; Severe Acute Respiratory Syndrome

Interventions

Ascorbic Acid

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Lung Injury; Respiration Disorders

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Results Point of Contact

• Title: Dr. Brian Davis
• Organization: Central Virginia VA Health Care System

Brian.Davis5@va.gov

804-675-5000

Study Officials

• Brian C Davis, MD

  Staff Physician, GI Division

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician

Model Details: Parallel: Participants are assigned to one of two or more groups in parallel for the duration of the study

Study Record Dates

• First Submitted: April 17, 2020
• First Posted: April 22, 2020
• Study Start: April 16, 2020
• Primary Completion: October 13, 2020
• Study Completion: October 13, 2020
• Last Updated: February 25, 2022
• Results First Posted: February 24, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)