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

COVID-19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04344184
• Other study ID #: HM20018977
• Status: Completed
• Phase: Phase 2
• Start date: December 18, 2020
• Est. completion date: June 10, 2022

Study information

• Verified date: March 2024
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: June 10, 2022
• Est. primary completion date: June 10, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• COVID-19
• Kidney Injury
• Lung Injury
• Lung Injury, Acute
• Wounds and Injuries

Intervention

Drug:
• L-ascorbic acid
50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours

Other:
• Placebo
Dextrose 5% Water

Locations

Country	Name	City	State
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Virginia Commonwealth University

Country where clinical trial is conducted

United States, 

References & Publications (10)

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. — View Citation

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. Erratum In: Lancet Infect Dis. 2020 Sep;20(9):e215. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: Crit Care Med. 2011 Aug;39(8):2022. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: JAMA. 2020 Jan 28;323(4):379. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Renal Safety Biomarkers - Serum Oxalate	Change in serum oxalate levels	On days 5,7 and 14
Secondary	Renal Safety Biomarkers - Urine Oxalate Stones	Microscopic analysis of urine for presence of oxalate stones	On days 5,7 and 14
Secondary	Renal Safety Biomarkers - 24-hour Urine Oxalate Levels	Renal safety will be Measured via renal safety biomarkers - 24- hour urine oxalate level	On days 5,7 and 14
Secondary	Acute Kidney Injury-free Days	Renal-failure free days, with AKI defined by the KDIGO criteria	Over 27 days from baseline
Secondary	Number of Deaths	Mortality by all cause was comprehensively collected using hospital encounter information over 27 days from baseline, in addition to public record review at day 60 and day 90. Results for this outcome represents the number of deaths that have occurred between each time point.	Over 27 days from baseline, day 60 and day 90 day
Secondary	Change in Plasma Ferritin Levels	Difference in plasma ferritin levels in ng/mL, compared to baseline levels	Day 0 (baseline), day 1, day 7
Secondary	Change in Plasma D-dimer Levels	Difference in D-dimer levels in mcg/mL, compared to baseline levels	Day 0 (baseline), days 1, 2, 3, 4, 5, 6, and 7
Secondary	Change in Serum Lactate Dehydrogenase (LDH) Levels	Difference in lactate dehydrogenase (LDH) levels in units/L, compared to baseline levels	Day 0 (baseline), days 1, 2, 3, 4, 5, 6 and 7
Secondary	Change in Plasma IL-6 Levels	Difference in plasma IL-6 levels in pg/mL, compared to baseline levels	Day 0 (baseline), days 1, 2, 3, 4, 5, 6 and 7
Secondary	Number of Patients Alive and Free of Respiratory Failure	Respiratory failure defined as resource utilization requiring at least 1 of the following: Endotracheal intubation and mechanical ventilation, Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen =0.5), noninvasive positive pressure ventilation, extracorporeal membrane oxygenation	At 28-days
Secondary	Number of Patients Alive and Free of Invasive Mechanical Ventilation	Number of patients alive and not requiring invasive mechanical ventilation. The results represent the number of patients who were ventilator free.	At 28-days