Original Investigation 

Caring for the Critically Ill Patient

High-Dose Intravenous Vitamin C and Mortality and Organ Dysfunction in Severe Burn Injury: The VICTORY Randomized Clinical Trial

Christian Stoppe, Aileen Hill, Leopoldo C. Cancio, et al

JAMA Published Online: June 10, 2026

doi: 10.1001/jama.2026.10616

Key Points

Question  Does high-dose intravenous vitamin C reduce a composite of 28-day mortality and persistent organ dysfunction in patients with severe burn injury?

Findings  In this randomized clinical trial that included 238 patients with severe burns, the primary composite outcome of 28-day mortality and persistent organ dysfunction occurred in 40.8% of patients in the intravenous vitamin C group compared with 29.7% in the placebo group. At the first prespecified interim analysis, this result crossed the futility/harm threshold, prompting early termination of the trial.

Meaning  High-dose intravenous vitamin C did not reduce mortality and organ dysfunction and may be associated with harm in patients with severe burn injury.

Abstract

Importance  Severe burn injury triggers systemic inflammation that can lead to multiple organ dysfunctions and death. High-dose intravenous vitamin C has been proposed to mitigate these effects, but strong evidence in patients with burn injury is lacking.

Objective  To evaluate the efficacy of high-dose intravenous vitamin C in patients with severe burn injury.

Design, Setting, and Participants  Randomized, double-blind, placebo-controlled phase 3 trial conducted across 24 burn centers in North, Central, and South America; Europe; and Asia. Adults (≥18 years) with deep second- and/or third-degree burns covering 20% or more of total body surface area and requiring skin grafting were enrolled between August 18, 2020, and September 12, 2025. Final follow-up was completed in March 2026. The trial was stopped early after the first prespecified interim analysis for futility/harm.

Interventions  Patients were randomly assigned (1:1) to receive intravenous vitamin C (50 mg/kg every 6 hours for 96 hours) or matched placebo.

Main Outcomes and Measures  The primary outcome was a composite of 28-day mortality and persistent organ dysfunction (defined as dependence on mechanical ventilation, kidney replacement therapy, or vasopressor/inotrope support at day 28). The main secondary outcome was time to discharge alive from hospital within 90 days.

Results  Among 238 patients enrolled (mean age, 48.9 [SD, 19.1] years; 79% male; mean total body surface area, 37.0% [SD, 14.6%]), 120 were assigned to vitamin C and 118 to placebo. The primary composite outcome occurred in 49 patients (40.8%) in the vitamin C group and 35 patients (29.7%) in the placebo group (adjusted risk ratio [RR], 1.28 [95% CI, 0.99-1.65]; P = .06), crossing the prespecified futility/harm threshold and prompting early trial termination. Time to discharge alive from hospital within 90 days was not improved (adjusted subdistribution hazard ratio, 0.85 [95% CI, 0.62-1.16]; P = .31). Twenty-eight–day mortality was higher in the vitamin C group (15.0% vs 7.6%; adjusted RR, 1.96 [95% CI, 1.32-2.90]; P = .001), as was hospital mortality (23.3% vs 16.1%; adjusted RR, 1.44 [95% CI, 1.03-2.00]; P = .03).

Conclusions and Relevance  Among patients with severe burn injury, high-dose intravenous vitamin C did not reduce 28-day mortality and persistent organ dysfunction and is possibly harmful.

Trial Registration  ClinicalTrials.gov Identifier: NCT04138394