Evaluation of High-Dose Intravenous Ascorbic Acid on Persistent Organ Dysfunction and Mortality in Patients with Severe Burn Injury: A Phase III Randomized Trial

The primary objective of the study is to evaluate the effect of high-dose intravenous **vitamin C** (50 mg/kg every 6 hours for 96 hours) in addition to the standard of care (SOC) on the 28-day composite outcome of Persistent Organ Dysfunction (POD) and all-cause mortality in patients with severe, life-threatening burn injuries. This objective is clinically relevant as it aims to determine whether the addition of vitamin C can improve survival rates and reduce organ dysfunction in this critically ill population.

Secondary objectives include assessing the impact of high-dose intravenous vitamin C on several clinical outcomes compared to placebo and SOC. These outcomes are: time to discharge alive from the hospital, hospital mortality, duration of stay in the intensive care unit (ICU) and hospital, 6-month mortality, health-related quality of life, and healthcare resource utilization. These objectives are important for understanding the broader implications of vitamin C treatment on patient recovery and healthcare system burden.

The clinical trial involves a total of **34 participants** who are **severely burned patients**. The study population includes both male and female subjects aged **18 years or older**. Participants are required to have deep 2nd and/or 3rd degree burns, necessitating skin grafting, with a minimum burn size of 20% Total Body Surface Area (TBSA). This trial specifically targets individuals with severe, life-threatening burn injuries, as these patients are at a higher risk of morbidity and mortality. The selection process ensures that only those who meet these criteria are included, emphasizing the need for significant fluid resuscitation. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The study population is considered vulnerable due to the critical nature of their health status. The sponsor has not provided additional information regarding other lifestyle factors or specific exclusion criteria.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the effect of high-dose intravenous **ascorbic acid** on severely burned patients. The trial aims to assess the impact of this intervention on a 28-day composite outcome of Persistent Organ Dysfunction (POD) and all-cause mortality, compared to a placebo and standard of care. The study is set to run from October 2022 to October 2026, with an estimated duration of four years. Participants will be involved in the study for a maximum of 96 hours of treatment, followed by a 28-day observation period.

The sequence of study visits includes an initial screening visit to confirm eligibility, based on criteria such as age (18 years or older), burn severity (deep 2nd and/or 3rd degree burns), and burn size (≥ 20% Total Body Surface Area). Following the screening, eligible participants will be randomized to receive either the active treatment or placebo. The treatment phase involves administering 50 mg/kg of ascorbic acid every 6 hours for 96 hours. Follow-up visits will occur to monitor the primary endpoint, which is the combination of being alive and free of organ support at 28 days. Secondary endpoints include time to discharge alive from the hospital and POD-free days within the first 28 days.

The end-of-study visit will occur at the conclusion of the 28-day follow-up period, where final assessments will be conducted. Participants may be withdrawn from the study early if they experience adverse effects that necessitate discontinuation, if they withdraw consent, or if they are lost to follow-up. The trial is conducted under strict ethical guidelines, ensuring the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of **ASCORBIC ACID** as the experimental medication. This substance is provided in the form of a solution for injection, specifically designed for intravenous administration. The dosing regimen for ascorbic acid is set at 50 mg/kg every 6 hours, with a maximum daily dose of 200 mg/kg and a total maximum dose of 800 mg/kg over the treatment period. The treatment duration is limited to 96 hours, equivalent to 4 days. The primary objective is to evaluate the effect of high-dose intravenous vitamin C on the 28-day composite outcome of Persistent Organ Dysfunction (POD) and all-cause mortality in patients with severe, life-threatening burn injuries.

In addition to the experimental treatment, the study includes the use of **D5W (dextrose 5% in water)** as a placebo. This solution is administered to participants in the control group to maintain blinding and ensure the integrity of the trial. The pharmaceutical form and specific administration details for D5W are not provided, but it is typically used as an intravenous solution in clinical settings.

Another non-experimental treatment used in the study is the **NaCl solution**, which serves as a standard-of-care therapy. The NaCl solution is commonly used for fluid and electrolyte replenishment in clinical practice. Similar to D5W, the pharmaceutical form and administration specifics are not detailed, but it is generally administered intravenously.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The trial is designed to assess the efficacy and safety of high-dose vitamin C in conjunction with standard care, compared to placebo and standard care alone, in improving outcomes for patients with severe burn injuries.

Efficacy in the clinical trial titled "VItamin C in Thermal injuRY: The VICToRY Trial" will be assessed using a primary endpoint and several secondary endpoints. The primary endpoint is a composite measure of **Persistent Organ Dysfunction (POD)** and all-cause mortality at 28 days. This endpoint combines the criteria of being alive and free of organ support, which includes inotropes or vasopressors, renal replacement therapy, and mechanical ventilation.

Secondary endpoints include the "time to discharge alive from hospital" and the individual components of the 28-day POD. These components encompass mortality, the use of inotropes or vasopressors, mechanical circulatory assistance, renal replacement therapy, mechanical ventilation, and the number of POD-free days within the first 28 days. The trial will involve the administration of high-dose intravenous vitamin C in addition to standard care, compared to a placebo with standard care, in patients with severe burn injuries. The efficacy parameters will be collected and analyzed at the 28-day mark to determine the impact of the treatment on the specified outcomes.