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

Phase 2

Completed

Conditions: COVID-19
Lung Injury, Acute
Kidney Injury

Interventions: Other: Placebo
Drug: L-ascorbic acid

Registration Number: NCT04344184

Lead Sponsor: Virginia Commonwealth University

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 47

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Dextrose 5% Water
Infusion	L-ascorbic acid	L-Ascorbic Acid (Vitamin C), intravenous infusion

Primary Outcome Measures

Name	Time	Method
Change in COVID Disease Status	Over 27 days from baseline, day 60 and day 90 day	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).

Secondary Outcome Measures

Name	Time	Method
Number of Patients Alive and Free of Respiratory Failure	At 28-days	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
Renal Safety Biomarkers - Urine Oxalate Stones	On days 5,7 and 14	Microscopic analysis of urine for presence of oxalate stones
Acute Kidney Injury-free Days	Over 27 days from baseline	Renal-failure free days, with AKI defined by the KDIGO criteria
Number of Deaths	Over 27 days from baseline, day 60 and day 90 day	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.
Change in Serum Lactate Dehydrogenase (LDH) Levels	Day 0 (baseline), days 1, 2, 3, 4, 5, 6 and 7	Difference in lactate dehydrogenase (LDH) levels in units/L, compared to baseline levels
Change in Plasma IL-6 Levels	Day 0 (baseline), days 1, 2, 3, 4, 5, 6 and 7	Difference in plasma IL-6 levels in pg/mL, compared to baseline levels
Number of Patients Alive and Free of Invasive Mechanical Ventilation	At 28-days	Number of patients alive and not requiring invasive mechanical ventilation. The results represent the number of patients who were ventilator free.
Renal Safety Biomarkers - Serum Oxalate	On days 5,7 and 14	Change in serum oxalate levels
Renal Safety Biomarkers - 24-hour Urine Oxalate Levels	On days 5,7 and 14	Renal safety will be Measured via renal safety biomarkers - 24- hour urine oxalate level
Change in Plasma Ferritin Levels	Day 0 (baseline), day 1, day 7	Difference in plasma ferritin levels in ng/mL, compared to baseline levels
Change in Plasma D-dimer Levels	Day 0 (baseline), days 1, 2, 3, 4, 5, 6, and 7	Difference in D-dimer levels in mcg/mL, compared to baseline levels