Design: randomised, double-blind, placebo-controlled phase 3 trial at 24 burn centres, stopped early for futility and harm (VICTORY)
Population: 238 adults with deep second- or third-degree burns over 20% or more of total body surface area requiring grafting; mean age 48.9, 79% male, mean burn area 37.0%
Primary outcome: composite of 28-day mortality and persistent organ dysfunction (ventilation, kidney replacement therapy or vasopressor dependence at day 28)
Effect: 40.8% vs 29.7% (adjusted RR 1.28; 95% CI 0.99-1.65; P = .06); 28-day mortality 15.0% vs 7.6% (adjusted RR 1.96; 1.32-2.90; P = .001)

VICTORY randomised 238 adults with deep second- or third-degree burns covering at least 20% of total body surface area and requiring grafting, across 24 burn centres on four continents, to intravenous vitamin C 50 mg/kg every six hours for 96 hours or matched placebo. The data monitoring committee stopped the trial at the first prespecified interim analysis, for futility and harm.

The primary composite — 28-day mortality plus persistent dependence on ventilation, kidney replacement therapy or vasopressors at day 28 — occurred in 40.8% of the vitamin C group and 29.7% of the placebo group. Twenty-eight-day mortality was 15.0% against 7.6%, and hospital mortality 23.3% against 16.1%.

The nephrological relevance is direct and often overlooked. High-dose intravenous ascorbate is metabolised to oxalate, and oxalate nephropathy from exactly this kind of regimen is a recognised cause of acute kidney injury that requires dialysis and does not always recover. Kidney replacement therapy dependence sat inside the harmed composite here.

This follows the same trajectory as high-dose vitamin C in sepsis, where enthusiasm ran ahead of randomised evidence and the eventual trials found no benefit and some harm. The pattern is worth noticing whenever a cheap, apparently benign micronutrient is proposed at pharmacological doses for a critical illness.

Do not give high-dose intravenous vitamin C for severe burns, in or out of a protocol
Where high-dose ascorbate has been given for any indication, watch creatinine closely and consider oxalate nephropathy in unexplained acute kidney injury
Remove it from local burns and sepsis order sets if it is still there
Distinguish this from replacing documented vitamin C deficiency, which is a different intervention at a different dose
Ask about intravenous vitamin C from outside sources in patients presenting with unexplained acute kidney injury; it is widely sold as a wellness infusion

Don't overread it

Effect sizes from a trial stopped at its first interim analysis are unstable; the direction of harm is convincing, the magnitude less so.

The statistics, in plain English

The primary composite gave an adjusted risk ratio of 1.28 with a 95% confidence interval of 0.99 to 1.65 and P = .06 — technically not significant, and it was the prespecified futility and harm boundary rather than a p-value that stopped the trial. The mortality signal is harder to dismiss: 1.96 (1.32-2.90) at 28 days and 1.44 (1.03-2.00) in hospital, both intervals clear of 1.0. Trials stopped early at an interim look tend to exaggerate effect sizes in whichever direction triggered the stop, so the true harm may be smaller than a doubling of mortality. What the data do not support is any argument that this is a chance finding to be waited out.