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

Study Overview
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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.

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

Conditions
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COVID-19, Lung Injury, Acute, Kidney Injury

Intervention / Treatment
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* Drug: L-ascorbic acid
* Other: Placebo


Participation Criteria
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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. 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 (see page 28). 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Infusion<br>L-Ascorbic Acid (Vitamin C), intravenous infusion | Drug: L-ascorbic acid<br>* 50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours<br>* Other names: Vitamin C, Intravenous;|
| Placebo Comparator: Placebo<br>Dextrose 5% Water | Other: Placebo<br>* Dextrose 5% Water<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in COVID disease status | COVID disease status will be measured by the 9-point (from 0 to 8) World Health Organization (WHO) ordinal scale for disease improvement at 28 days. | Baseline to 28, 60 and 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal safety biomarkers - serum oxalate | Change in serum oxalate levels | On days 5,7 and 14 | 
| Renal safety biomarkers - urine oxalate stones | Microscopic analysis of urine for presence of oxalate stones | On days 5,7 and 14 | 
| Renal safety biomarkers - 24-hour urine oxalate levels | 24-hour urine oxalate levels | On days 5,7 and 14 | 
| Acute Kidney Injury-free days | Renal-failure free days, with AKI defined by the KDIGO criteria | On day 28, 90 | 
| Number of deaths | Mortality by all causes | On day 28, 60 and 90 days | 
| Change in plasma ferritin levels | Difference in plasma ferritin levels in ng/mL, compared to baseline levels | Days 1-7 compared with baseline | 
| Change in plasma D-dimer levels | Difference in D-dimer levels in mcg/mL, compared to baseline levels | Days 1-7 compared with baseline | 
| Change in serum lactate dehydrogenase (LDH) levels | Difference in lactate dehydrogenase (LDH) levels in units/L, compared to baseline levels | Days 1-7 compared with baseline | 
| Change in plasma IL-6 levels | Difference in plasma IL-6 levels in pg/mL, compared to baseline levels | Days 1-7 compared with baseline | 
| Proportion 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 | 
| Proportion of patients alive and free of invasive mechanical ventilation | Percentage of patients alive and not requiring invasive mechanical ventilation | At 28-days |