Early Infusion of Vitamin C for Treatment of Novel COVID-19 Acute Lung Injury (EVICT-CORONA-ALI)
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|ClinicalTrials.gov Identifier: NCT04344184|
Recruitment Status : Not yet recruiting
First Posted : April 14, 2020
Last Update Posted : April 24, 2020
|Condition or disease||Intervention/treatment||Phase|
|COVID-19 Lung Injury, Acute||Drug: L-ascorbic acid Other: Placebo||Phase 2|
In December 2019, a cluster of pneumonia cases was reported in Wuhan, China, and a novel coronavirus, SARS-Cov-2, was identified. The World Health Organization (WHO) designated the respiratory disease as coronavirus disease (COVID-19) on February 12, 2020. Numerous reports have since characterized the COVID-19 clinical syndrome, ranging from asymptomatic/mild disease to severe disease leading to respiratory failure requiring mechanical ventilation (i.e., ARDS, multi-organ failure, sepsis, and death).
A safe, effective, and inexpensive therapy is urgently needed, one that can alter the natural course of the disease process and reduce strain on healthcare systems. High Dose Intravenous Vitamin C is a safe and possibly effective treatment for ARDS and has been described to be effective for ARDS of viral origin.
A double-blind, placebo-controlled randomized control trial involving 167 patients with ARDS who were randomized to receive 50 mg/kg every 6 hours of HDIVC for 4 days versus placebo showed a statistically significant difference in 28-day all-cause mortality. The 28-day mortality was 29.8% in the vitamin C group versus 46.3% in the placebo group, although this was a secondary outcome.
This can be translated as a Number Needed to Treat (NNT) of 6-8 patients to save one life from ARDS. The statistical effect on mortality remained up to 60-days following trial completion.
The first study, published in 1986, treated 16 ARDS patients with intravenous vitamin C (1000 mg IV every 6 hours) plus antioxidants versus 16 ARDS patients who received the standard care at that time (i.e., control group). There was a reduction in mortality in the vitamin C group: 37% versus 71% in the standard care group (p<0.01). A phase I trial in 2014 proved that plasma vitamin C in patients with severe sepsis and ARDS were low, almost at scorbutic levels and that HDIVC administration had a dose-dependent effect in the prevention of multi-organ failure, as measured by the Sequential Organ Failure Assessment (SOFA) scores.
Patients who received a total of 200 mg/kg/day of HDIVC for 4 days (administered in 50 mg/kg/dose, every 6 hours), had significantly lower organ failure scores than placebo, and even lower scores than the patients who received lower-doses of IV vitamin C (50 mg/kg/day administered at 12.5 mg/kg/dose, every 6 hours for 4 days). In this trial, the patients in the HDIVC group (200 mg/kg/day) achieved plasma levels up to 3,000 µM on day 4.
To assess the treatment effect of a 72-hour intravenous vitamin C infusion protocol (100 mg/kg every 8 hours) in patients with hypoxemia and suspected COVID-19 (Novel Coronavirus ID-19). In the course of performing this phase 2 trial researchers will explore three following hypotheses:
Primary Endpoint: HDIVC infusion will increase 28-day ventilator-free days. Secondary Endpoint A: HDIVC infusion will reduce 28-day all-cause hospital mortality.
Secondary Endpoint B: HDIVC infusion will significantly increase acute inflammation-free days (defined as CRP >=10 mg/L) among COVID-19 patients.
Secondary Endpoint C: HDIVC infusion will be safe, as demonstrated by organ-failure-free days up to 28 days.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||200 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Early Infusion of Vitamin C for Treatment of Novel Coronavirus Acute Lung Injury (EVICT-CORONA-ALI)|
|Estimated Study Start Date :||June 2020|
|Estimated Primary Completion Date :||May 2021|
|Estimated Study Completion Date :||May 2021|
Active Comparator: Infusion
L-Ascorbic Acid (Vitamin C), intravenous infusion
Drug: L-ascorbic acid
100 mg/kg intravenous vitamin C infusion every 8 hours for up to 72 hours
Other Name: Vitamin C, Intravenous
Placebo Comparator: Standard of care
Dextrose 5% Water
Dextrose 5% Water
- Number of ventilator-free days [ Time Frame: Up to 28 days ]Documented days free off mechanical ventilation the first 28 days post enrollment
- All-cause-mortality [ Time Frame: Up to 28 days ]Mortality at 28-days by all causes
- Acute-inflammation-free days [ Time Frame: Up to 28 days ]Number of days free of acute inflammation (defined as CRP >= 10 mg/L)
- Organ-failure-free days [ Time Frame: Up to 1 year ]Number of days that the participant is free of organ failure in ALL of the following organ systems: Cardiovascular, Respiratory, Neurological, Liver, Bone marrow organ, Renal
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04344184
|Contact: Markos G Kashiouris, MD MPHemail@example.com|
|Contact: Alpha (Berry) A Fowler, III, MDfirstname.lastname@example.org|
|United States, Virginia|
|Hunter Holmes McGuire VA Medical Center|
|Richmond, Virginia, United States, 23249|
|Contact: Brian Davis, MD email@example.com|
|Virginia Commonwealth University|
|Richmond, Virginia, United States, 23298|
|Principal Investigator:||Markos G Kashiouris, MD MPH||Virginia Commonwealth University|
|Study Director:||Brian Davis, MD||Hunter Holmes McGuire VA Medical Center - Richmond, VA|