High-dose vitamin C didn't help severe burn patients, and may have raised deaths

High-dose intravenous vitamin C has drifted in and out of critical-care fashion for years, pitched as a cheap antioxidant that might blunt the runaway inflammation of sepsis, shock, and major burns. The evidence has been thin and contradictory. A phase 3 trial in severe burn injury has now added the strongest data yet, and it points the wrong way for the intervention [s1].

What the trial did

VICTORY was a randomised, double-blind, placebo-controlled phase 3 trial run across 24 burn centres in North, Central, and South America, Europe, and Asia [s1]. It enrolled adults aged 18 or older with deep second- and/or third-degree burns covering 20% or more of total body surface area and requiring skin grafting, between August 18, 2020, and September 12, 2025, with final follow-up in March 2026 [s1].

Patients were assigned 1:1 to intravenous vitamin C at 50 mg/kg every six hours for 96 hours, or matched placebo [s1]. The primary outcome was a composite of 28-day mortality and persistent organ dysfunction — dependence on mechanical ventilation, kidney replacement therapy, or vasopressor or inotrope support at day 28 [s1]. The main secondary outcome was time to discharge alive from hospital within 90 days [s1].

The rationale was specific to burns. A severe burn triggers systemic inflammation that can cascade into multiple organ dysfunction and death, and high-dose vitamin C had been proposed to mitigate those effects — but, as the authors note, strong evidence in burn patients was lacking [s1]. That is the vacuum a phase 3 trial is built to fill: a large, blinded, placebo-controlled test of an intervention that had spread on plausibility more than proof.

The trial was led, per its registration, by the Clinical Evaluation Research Unit at Kingston General Hospital, an academic group, with the University of Wuerzburg as a collaborator [s2]. This is not a manufacturer's study of its own product — the intervention is a generic vitamin — which makes the negative result harder to attribute to sponsor bias.

What it found

The trial was stopped early, at the first prespecified interim analysis, for futility and harm [s1].

Among 238 patients enrolled (mean age 48.9 years, 79% male, mean total body surface area burned 37.0%), 120 were assigned to vitamin C and 118 to placebo [s1]. The primary composite outcome occurred in 49 patients (40.8%) in the vitamin C group and 35 (29.7%) in the placebo group — an adjusted risk ratio of 1.28 (95% CI, 0.99 to 1.65; P=.06), which crossed the prespecified futility/harm threshold and prompted termination [s1].

Time to discharge alive within 90 days was not improved (adjusted subdistribution hazard ratio 0.85; 95% CI, 0.62 to 1.16; P=.31) [s1].

The mortality signal is the part that turns this from a null result into a caution. Twenty-eight-day mortality was higher in the vitamin C group, 15.0% versus 7.6% (adjusted risk ratio 1.96; 95% CI, 1.32 to 2.90; P=.001), as was in-hospital mortality, 23.3% versus 16.1% (adjusted risk ratio 1.44; 95% CI, 1.03 to 2.00; P=.03) [s1].

How to read a harm signal from a stopped trial

Two cautions cut in opposite directions. Trials halted early for harm can exaggerate the size of an effect, because they stop at a moment when the numbers look worst; the true excess risk may be smaller than 15.0% versus 7.6% suggests. But the direction is consistent across the primary composite, 28-day mortality, and hospital mortality [s1], and consistency across related endpoints is harder to dismiss than a single outlier. The authors' own conclusion is measured: vitamin C did not reduce death or organ dysfunction and is "possibly harmful" [s1].

The limits, stated plainly

This is one trial of 238 patients, smaller than planned because it was stopped, in a specific population — adults with large burns requiring grafting [s1]. It does not speak to vitamin C in sepsis, in smaller burns, or at different doses or durations, and it does not establish the mechanism of the excess deaths. Early stopping widens the confidence intervals and limits how firmly any single number should be read [s1].

What it means and what to watch

The practical takeaway is narrow but clear: in severe burns, the specific regimen tested — 50 mg/kg every six hours for 96 hours — did not help and was associated with more deaths, so there is no support here for adding it to burn care [s1]. Whether the harm signal reflects something particular to burns, to this dose, or to intravenous ascorbate in acutely inflamed patients generally is the open question. The registry lists the study status as suspended, consistent with the early termination [s2].

This article describes trial results, including doses and mortality data, for informational purposes only. It is not medical advice and not a recommendation about any treatment.

Sources

• [s1] Stoppe C, Hill A, Cancio LC, et al; VICTORY Study Team. High-Dose Intravenous Vitamin C and Mortality and Organ Dysfunction in Severe Burn Injury: The VICTORY Randomized Clinical Trial. JAMA, published online 2026 (created 2026-06-10).
• [s2] ClinicalTrials.gov. VItamin C in Thermal injuRY: The VICToRY Trial. NCT04138394, last update posted 2026-04-06.