High-Dose IV Vitamin C Fails to Improve Outcomes in Severe Burns: JAMA

A highly robust, double-blind, randomized control phase 3 clinical trial that involved the recruitment of adult patients above 18 years old who had been affected by deep second and/or third degree burns that covered a large extent of at least 20% of their Total Body Surface Area (TBSA). All patients in the trial were required to have skin grafting interventions. Recruitment of study subjects began on August 18, 2020, and lasted until September 12, 2025, with the last data collected in March 2026. Patients were randomized in equal proportions to either receive treatment with high doses of intravenous vitamin C at 50 mg/kg every six hours for 96 consecutive hours, or to receive equivalent volume of placebo.

The primary efficacy endpoint was the combined outcome measure of 28-day mortality and sustained organ dysfunction. Sustained organ dysfunction, in particular, referred to any continued reliance on mechanical ventilation, kidney replacement therapy, and vasopressor or inotropic support at Day 28. Importantly, the study had to be stopped early based on the results of an interim analysis that revealed crossing of a predetermined threshold for futility and harm to patients.

Key findings:

• For the international phase 3 trial, the total randomization of patients who received the vitamin C treatment or placebo was 238 critically burned adults in 24 sites worldwide.
• The final analysis cohort consisted of an equal division of patients, including 120 randomly allocated for treatment with high-dose IV vitamin C and 118 patients randomized for treatment with placebo.
• The mean age of all included patients was 48.9 years (SD, 19.1), there was significant male gender skewness (79% males), and a mean severe burn size covered 37.0% (SD, 14.6%) of total body surface area.
• For the combined endpoint, mortality or persistence of organ support by day 28, 40.8% of patients (49 of 120) experienced this outcome in the vitamin C group versus 29.7% (35 of 118) in the placebo group, resulting in an adjusted RR of 1.28 (95% CI, 0.99-1.65; P = 0.06).
• With respect to time to hospital discharge alive during a 90-day period, no statistical difference was noted, leading to an adjusted sub distribution hazard ratio of 0.85 (95% CI, 0.62-1.16; P=0.31).
• The exact 28-day mortality rate was almost twice that of the treated patients (15.0%) when compared to the placebo (7.6%), indicating an increased risk ratio of 1.96 (95% CI, 1.32-2.90; P=0.001).
• The overall in-hospital mortality increased significantly to 23.3%, when compared to the placebo group mortality rate of 16.1%, giving rise to an adjusted risk ratio of 1.44 (95% CI, 1.03-2.00; P=0.03).

In summary, administration of high dose IV ascorbic acid in patients suffering from burn injuries did not decrease mortality and organ dysfunction after 28 days, but is perhaps even detrimental to the patient’s health. This prematurely ended Phase III trial acts as a very important reminder that even popularly known and trusted vitamins can become dangerous at extremely high dosages.

Reference:

Stoppe C, Hill A, Cancio LC, et al. High-Dose Intravenous Vitamin C and Mortality and Organ Dysfunction in Severe Burn Injury: The VICTORY Randomized Clinical Trial. JAMA. Published online June 10, 2026. doi:10.1001/jama.2026.10616