SAFEty Study of Early Infusion of Vitamin C for Treatment of Novel Coronavirus Acute Lung Injury (SAFE EVICT CORONA-ALI)

NCT04344184 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HM20018977
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety of a 96-hour intravenous vitamin C infusion protocol (50 mg/kg every 6 hours) in patients with hypoxemia and suspected COVID-19.

Conditions

COVID-19; Lung Injury, Acute; Kidney Injury

Outcome Measures

Primary Outcomes (1)

• Change in COVID Disease Status

  COVID disease status was measured for improvement using the World Health Organization (WHO) ordinal scale for clinical improvement of COVID-19 over ICU admission within 27 days. The WHO scale is a 9-point ordinal scale ranging from uninfected (0), ambulatory (1-2), hospitalized with severe disease (5), hospitalized with intubation and organ support (6-7) and death (score of 8).

  Over 27 days from baseline, day 60 and day 90 day

Secondary Outcomes (11)

• Renal Safety Biomarkers - Serum Oxalate

  On days 5,7 and 14

• Renal Safety Biomarkers - Urine Oxalate Stones

  On days 5,7 and 14

• Renal Safety Biomarkers - 24-hour Urine Oxalate Levels

  On days 5,7 and 14

• Acute Kidney Injury-free Days

  Over 27 days from baseline

• Number of Deaths

  Over 27 days from baseline, day 60 and day 90 day

Study Arms (2)

Infusion

ACTIVE COMPARATOR

L-Ascorbic Acid (Vitamin C), intravenous infusion

Drug: L-ascorbic acid

Placebo

PLACEBO COMPARATOR

Dextrose 5% Water

Other: Placebo

Interventions

L-ascorbic acid DRUG

50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours

Also known as: Vitamin C, Intravenous

Infusion

Placebo OTHER

Dextrose 5% Water

Placebo

Eligibility Criteria

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

You may qualify if:

• Adults of 18 years or older
• Patients hospitalized with a diagnosis of COVID-19 based on central laboratory-confirmed COVID-19 Novel Coronavirus Disease-2019, based on a positive SARS-CoV-2 RT-PCR confirmed within 72 hours prior to enrollment of nasal, oropharyngeal, or BAL specimen with hypoxemia, (i.e., decrease in oxygenation, as outlined below)
• Pulse oximetry saturation (SpO2) \< 93% on room air in WHO COVID-19 ordinal scale 3 patients, regardless the need for assisted ventilation, or oxygenation.
• Any new requirement of supplemental oxygen, with any oxygen device (WHO COVID-19 ordinal scale 4-7, regardless of pulse oximetry reading)
• In patients with supplemental oxygen at home, any increase in the requirement of supplemental oxygen.
• In ICU level care

You may not qualify if:

• Age less than 18 years
• Known allergy to Vitamin C
• Inability to obtain consent from patient or next of kin
• Presence of diabetic ketoacidosis
• ANY history of oxalate stones at any time
• Patients with Kidney Disease Improving Global Outcomes (KDIGO), CKD stage 4 (eGFR \< 30 ml/min, CKD stage 5 and end-stage renal disease on dialysis patients are excluded.
• Patients with Acute Kidney Injury, stage 3.
• Pregnant, or lactating
• Known diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Patients who received the following medications within 7 days prior to enrollment, or plan to receive during enrollment, or 7 days after enrollment: aluminum hydroxide, bortezomib, copper, deferoxamine, amphetamines including derivatives such as fluphenazine.
• Patients with active sickle cell crisis
• Prisoners
• Patients outside ICU level care

Sponsors & Collaborators

• Virginia Commonwealth University: lead

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Publications (10)

• Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis. 2020 May;20(5):533-534. doi: 10.1016/S1473-3099(20)30120-1. Epub 2020 Feb 19. No abstract available.

  PMID: 32087114 BACKGROUND

• 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

• 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

• 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, Seropian IM, Kraskauskas D, Thakkar JN, Voelkel NF, Fowler AA 3rd, Natarajan R. Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury. Crit Care Med. 2011 Jun;39(6):1454-60. doi: 10.1097/CCM.0b013e3182120cb8.

  PMID: 21358394 BACKGROUND

• Fisher BJ, Kraskauskas D, Martin EJ, Farkas D, Wegelin JA, Brophy D, Ward KR, Voelkel NF, Fowler AA 3rd, Natarajan R. Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid. Am J Physiol Lung Cell Mol Physiol. 2012 Jul 1;303(1):L20-32. doi: 10.1152/ajplung.00300.2011. Epub 2012 Apr 20.

  PMID: 22523283 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

• Agathocleous M, Meacham CE, Burgess RJ, Piskounova E, Zhao Z, Crane GM, Cowin BL, Bruner E, Murphy MM, Chen W, Spangrude GJ, Hu Z, DeBerardinis RJ, Morrison SJ. Ascorbate regulates haematopoietic stem cell function and leukaemogenesis. Nature. 2017 Sep 28;549(7673):476-481. doi: 10.1038/nature23876. Epub 2017 Aug 21.

  PMID: 28825709 BACKGROUND

• Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.

  PMID: 32091533 BACKGROUND

MeSH Terms

Conditions

COVID-19; Acute Lung Injury

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; Lung Injury

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Alpha Fowler
• Organization: Virginia Commonwealth University

alpha.fowler@vcuhealth.org

(804) 519-4369

Study Officials

• Alpha (Berry) A Fowler, III, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

• Brian Davis, MD

  Hunter Holmes McGuire VA Medical Center - Richmond, VA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2020
• First Posted: April 14, 2020
• Study Start: December 18, 2020
• Primary Completion: June 10, 2022
• Study Completion: June 10, 2022
• Last Updated: April 4, 2024
• Results First Posted: April 4, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)