High-dose intravenous vitamin C did not reduce mortality or persistent organ dysfunction among patients with severe burn injury in a recent trial.
In the international, double-blind, placebo-controlled, phase 3 randomized controlled VICTORY trial, researchers enrolled 238 adult patients with deep second- or third-degree burns covering at least 20% of their total body surface area and requiring skin grafting. The patients were recruited from 24 burn centers across North, Central, and South America; Europe; and Asia between August 18, 2020, and September 12, 2025. The participants were randomly assigned to receive either intravenous vitamin C at 50 mg/kg every 6 hours for 96 hours or matched placebo.
The primary endpoint was a composite of 28-day mortality and persistent organ dysfunction, defined as dependence on mechanical ventilation, kidney replacement therapy, or vasopressor or inotrope support at day 28. The primary outcome occurred in about 41% of patients who received high-dose vitamin C and 30% of those who received placebo. The adjusted risk ratio crossed the protocol-defined futility/harm threshold—an adjusted risk ratio greater than 1.1 favoring placebo—prompting the data and safety monitoring board to recommend terminating the trial at the first prespecified interim analysis.
In an accompanying editorial, David G. Greenhalgh, MD, of the Department of Burns at Shriners Children's Northern California and the Department of Surgery at the University of California, Davis, wrote: "High-dose intravenous vitamin C administered early after injury did not reduce organ dysfunction or [mortality] and should not be a treatment in severe burns."
The researchers noted that 28-day mortality was 15% among patients assigned to vitamin C compared with about 8% among patients assigned to placebo. Hospital mortality was 23% vs 16%, respectively, and intensive care unit mortality was 23% vs 15%. Six-month mortality was 26% in the vitamin C group and 20% in the placebo group.
The trial's main secondary outcome, time to discharge alive from the hospital within 90 days, also did not improve with vitamin C treatment. The cumulative incidence of discharge alive by 90 days was 66% in the vitamin C group compared with 71% in the placebo group. Persistent organ dysfunction–free days also showed no improvement with vitamin C treatment.
The researchers reported no evidence of benefit in any prespecified subgroup analysis, including analyses stratified by age, burn size, severity, and timing of treatment initiation. No statistically significant treatment-by-subgroup interactions were identified.
The study was designed to evaluate high-dose intravenous vitamin C in patients with severe burn injury, an area in which the researchers noted that strong evidence has been lacking. They stated that earlier studies reporting reductions in fluid requirements and ventilator duration were generally small, single-center studies that were underpowered for patient-centered outcomes such as mortality and persistent organ dysfunction. Some international nutrition guidelines have suggested micronutrient supplementation, including vitamin C, among patients with major burns.
The researchers discussed several possible explanations for the findings. They noted that vitamin C metabolism produces oxalate, which may contribute to kidney injury, and suggested that supraphysiologic dosing could disrupt redox signaling in critically ill patients. Kidney replacement therapy was initiated in 11% of patients assigned to vitamin C compared with 6% of patients assigned to placebo.
Full disclosures of the study authors can be found in the published study. Greenhalgh reported no conflicts of interest.