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

NCT ID: NCT04344184

Last Updated: 2024-04-04

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-18

Study Completion Date

2022-06-10

Brief Summary

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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.

Detailed Description

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The intravenous vitamin C treatment protocol will be comprised of four intravenous infusions a day, that is 50 mg/kg every 6 hours in patients with laboratory-confirmed SARS-CoV-2 infection manifesting COVID-19 (Novel Coronavirus Disease 2019) with hypoxemia. Treatment protocol will continue for 4 days (96 hours), and, if needed, the last study-specific bloodwork with being collected on day 7. All subjects will be followed to day 28 (phase I) and day 90 (phase II) for collection of clinical outcomes data through electronic health records (EHR) even though the treatment protocol will be completed by 96 hours from randomization at the latest. Secondary outcome data will also be collected either during in-person (clinic) visit or via telephone at the 60 and 90-day follow-up.

Conditions

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COVID-19 Lung Injury, Acute Kidney Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Infusion

L-Ascorbic Acid (Vitamin C), intravenous infusion

Group Type ACTIVE_COMPARATOR

L-ascorbic acid

Intervention Type DRUG

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

Placebo

Dextrose 5% Water

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Dextrose 5% Water

Interventions

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L-ascorbic acid

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

Intervention Type DRUG

Placebo

Dextrose 5% Water

Intervention Type OTHER

Other Intervention Names

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Vitamin C, Intravenous

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Virginia Commonwealth University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alpha (Berry) A Fowler, III, MD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Brian Davis, MD

Role: STUDY_DIRECTOR

Hunter Holmes McGuire VA Medical Center - Richmond, VA

Locations

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Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 32087114 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31573637 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32096845 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31978969 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24484547 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21358394 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22523283 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23917525 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28825709 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32091533 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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HM20018977

Identifier Type: -

Identifier Source: org_study_id

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