VItamin C in Thermal injuRY: The VICToRY Trial

Study Overview
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Brief Summary
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This study aims to show that giving high dose, intravenous vitamin C in addition to standard care to burned critically ill patients will be associated with less organ dysfunction, improved survival and a quicker rate of recovery. In this study, all patients will receive standard care and of the patients will also receive high dose intravenous vitamin C, while the other half of patients will receive placebo.

Detailed Description
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In certain disease states, such as those associated with severe burns and other critical illnesses, the relationship between nutrient deficiencies, altered immune status, and acquired infection has been recognized for many years. More than in any other injury, the inflammation and catabolism associated with severe burns can exacerbate nutrient deficiencies, thereby predisposing patients to impaired immune function and increased risk of developing infectious complications, organ dysfunction, and death. We aim to conduct a large-scale, multi-center randomized trial to evaluate the effect of high-dose (50mg/kg every 6 hours for 96 hours) intravenous vitamin C in addition to standard of care (SOC) on 28-days composite outcome of Persistent Organ Dysfunction (POD) and all-cause mortality compared to add-on placebo and SOC. Patients will be allocated to 2 groups, active or control: patients in the active group will receive intravenous vitamin C at 50mg/kg every 6 hrs for 96 hrs. Patients in the control group will receive a similar amount of placebo (either D5W or saline) delivered in the same manner as the vitamin C. This study will be the first large international multi-centre trial examining the effects of high dose intravenous vitamin C in burn patients. It represents a unique collaboration of burn units worldwide that is coordinated by the Clinical Evaluation Research Unit, based in Kingston Ontario Canada, a coordinating center that has demonstrated the ability to run multi-center trials and translate findings into practice.

Official Title
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VItamin C in Thermal injuRY: The VICToRY Trial A Phase III Multi-center Randomized Trial

Conditions
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Shock, Thermal Burn

Intervention / Treatment
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* Drug: Ascorbic Acid
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Deep 2nd and/or 3rd degree burns requiring skin grafting Minimum burn size of ≥ 20% Total Body Surface Area (TBSA) Exclusion Criteria: >24 hours from admission to participating hospital to consent. Patients admitted to burn unit >24 from injury or accident. Patients who are moribund (not expected to survive the next 72 hours). Pregnancy (pregnancy will be ruled out as part of standard of care) or lactating. Enrollment in another industry sponsored ICU intervention study. Receiving high-dose IV vitamin C already (enteral or oral vitamin C is allowed). Known glucose-6-phosphate dehydrogenase (G6PD) deficiency. Recent history of kidney stones (within the last year). Concomitant use of hydroxycobalamin (vitamin B12) for suspected cyanide poisoning.

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: Single Group Assignment
Interventional Model Description: Patients will be allocated to receive intravenous vitamin C at 50mg/kg, every 6 hrs for 96 hrs or placebo. We justify this proposed dosing strategy as the proposed dose of vitamin C has been shown to be safe and effective in patients with sepsis and lung injury whereas prior dosing strategies used in the burns literature (66 mg/kg/24 hours) have safety issues and are not long enough in duration. Control group: patients will receive a similar amount of placebo (either D5W or saline) delivered in the same manner as the vitamin C.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin C<br>Patients will receive intravenous vitamin C at 50mg/kg every 6 hours for 96 hours | Drug: Ascorbic Acid<br>* Patients will receive intravenous vitamin C (50 mg/kg every 6 hours for 96 hours).<br>* Other names: vitamin C;|
| Placebo Comparator: Control group<br>Patients will receive a similar amount of placebo (either D5W or saline) delivered in the same manner as the vitamin C. | Drug: placebo<br>* Patients will receive a similar amount of placebo (either D5W or saline) delivered in the same manner as the vitamin C.<br>* Other names: D5W;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistent Organ Dysfunction + Death | Persistent organ dysfunction (PODS)+death, a novel composite endpoint that combines being alive and being free of organ support (inotropes or vasopressors, renal replacement therapy and mechanical ventilation) | at 28 days | 
| Time to discharge alive from hospital | Time to discharge alive from hospital, a composite of mortality and length of stay is similar to ventilator- free days, which is a widely accepted and commonly used outcome in intensive care research. | 90 days |