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.
Stoppe et al. (Wed,) studied this question.