Clinical trial NCT04344184: SAFEty Study of Early Infusion of Vitamin C for Treatment of Novel Coronavirus Acute Lung Injury (SAFE EVICT CORONA-ALI)
Official title: SAFEty Study of Early Infusion of Vitamin C for Treatment of Novel Coronavirus Acute Lung Injury (SAFE EVICT CORONA-ALI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Lung Injury, Acute
Kidney Injury
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
First posted: 2020-04-14
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in COVID Disease Status
timeFrame: Over 27 days from baseline, day 60 and day 90 day
Secondary outcomes:
measure: Renal Safety Biomarkers - Serum Oxalate
timeFrame: On days 5,7 and 14
measure: Renal Safety Biomarkers - Urine Oxalate Stones
timeFrame: On days 5,7 and 14
measure: Renal Safety Biomarkers - 24-hour Urine Oxalate Levels
timeFrame: On days 5,7 and 14
measure: Acute Kidney Injury-free Days
timeFrame: Over 27 days from baseline
measure: Number of Deaths
timeFrame: Over 27 days from baseline, day 60 and day 90 day
measure: Change in Plasma Ferritin Levels
timeFrame: Day 0 (baseline), day 1, day 7
measure: Change in Plasma D-dimer Levels
timeFrame: Day 0 (baseline), days 1, 2, 3, 4, 5, 6, and 7
measure: Change in Serum Lactate Dehydrogenase (LDH) Levels
timeFrame: Day 0 (baseline), days 1, 2, 3, 4, 5, 6 and 7
measure: Change in Plasma IL-6 Levels
timeFrame: Day 0 (baseline), days 1, 2, 3, 4, 5, 6 and 7
measure: Number of Patients Alive and Free of Respiratory Failure
timeFrame: At 28-days
measure: Number of Patients Alive and Free of Invasive Mechanical Ventilation
timeFrame: At 28-days
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Alpha (Berry) A Fowler, III, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hunter Holmes McGuire VA Medical Center - Richmond, VA
name: Brian Davis, MD
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
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.
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.
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.
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.
citation: 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.
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.