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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
Sponsor:
Information provided by (Responsible Party):
Virginia Commonwealth University

Brief Summary:
This study will test to see if a 72-hour intravenous vitamin C infusion protocol (100 mg/kg every 8 hours) in patients with hypoxemia and suspected COVID-19 will reduce the lung injury caused by the SARS-Cov-2.

Condition or disease Intervention/treatment Phase
COVID-19 Lung Injury, Acute Drug: L-ascorbic acid Other: Placebo Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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


Arm Intervention/treatment
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
Other: Placebo
Dextrose 5% Water




Primary Outcome Measures :
  1. Number of ventilator-free days [ Time Frame: Up to 28 days ]
    Documented days free off mechanical ventilation the first 28 days post enrollment


Secondary Outcome Measures :
  1. All-cause-mortality [ Time Frame: Up to 28 days ]
    Mortality at 28-days by all causes

  2. Acute-inflammation-free days [ Time Frame: Up to 28 days ]
    Number of days free of acute inflammation (defined as CRP >= 10 mg/L)

  3. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients hospitalized with a diagnosis of COVID-19 based on positive RT-PCR of nasal, oropharyngeal, or BAL specimen with hypoxemia, (i.e., decrease in oxygenation, as outlined below)
  • New pulse oximetry saturation < 93% on room air OR
  • Any new requirement of supplemental oxygen, with any device
  • In patients with supplemental oxygen at home, any increase in the requirement of supplemental oxygen.

Exclusion Criteria:

  • Known allergy to Vitamin C
  • Inability to obtain consent from patient or next of kin
  • Presence of diabetic ketoacidosis
  • Active kidney stone(s)
  • Pregnant
  • Incarcerated

Information from the National Library of Medicine

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


Contacts
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Contact: Markos G Kashiouris, MD MPH 804-305-7187 mkashiouris@vcu.edu
Contact: Alpha (Berry) A Fowler, III, MD 804-828-9071 alpha.fowler@vcuhealth.org

Locations
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United States, Virginia
Hunter Holmes McGuire VA Medical Center
Richmond, Virginia, United States, 23249
Contact: Brian Davis, MD       brian.davis1@vcuhealth.org   
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
Investigators
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Principal Investigator: Markos G Kashiouris, MD MPH Virginia Commonwealth University
Study Director: Brian Davis, MD Hunter Holmes McGuire VA Medical Center - Richmond, VA
Publications:

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Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT04344184    
Other Study ID Numbers: HM20018977
First Posted: April 14, 2020    Key Record Dates
Last Update Posted: April 24, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no default plan to share individual participant data. May be considered upon reaching the VCU IRB

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Lung Injury
Acute Lung Injury
Respiratory Distress Syndrome, Adult
Wounds and Injuries
Lung Diseases
Respiratory Tract Diseases
Thoracic Injuries
Respiration Disorders
Ascorbic Acid
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents