For years, high-dose intravenous vitamin C has been positioned as a promising adjunct therapy in critical care — appealing in theory because of its antioxidant and anti-inflammatory properties. The VICTORY trial now delivers the strongest evidence yet that this intervention does not benefit — and may harm — patients with severe burns, a finding that carries immediate clinical implications and broader lessons for the supplement-in-critical-care hypothesis.
The VICTORY trial was a rigorous phase 3, double-blind, placebo-controlled study spanning 24 burn centers across five continents. Adults with deep second- or third-degree burns covering at least 20% of total body surface area were randomized to receive intravenous vitamin C at 50 mg/kg every six hours for 96 hours or a matched placebo. The composite primary outcome — 28-day mortality combined with persistent organ dysfunction (defined as ongoing dependence on mechanical ventilation, kidney replacement therapy, or vasopressor support at day 28) — was tracked in 238 enrolled patients. Critically, the trial was stopped early at its first prespecified interim analysis due to futility and signals of potential harm, meaning the intervention not only failed to demonstrate benefit but raised safety concerns sufficient to halt enrollment.
This result is particularly significant given the mechanistic plausibility that drove earlier enthusiasm. Observational data and small trials had suggested that high-dose vitamin C might attenuate capillary leak and reduce resuscitation fluid volumes in burns — a hypothesis that gained traction in the COVID-19 critical care literature as well. VICTORY's design was specifically powered to test this in the burn context with appropriate rigor. The early termination for harm is a sobering counter-signal to that optimism. Limitations include the relatively modest sample size at stopping (n=238) and the possibility that subgroups — such as patients with specific burn depths or surface areas — might respond differently. Still, as a phase 3 multicenter RCT published in JAMA, this represents potentially paradigm-shifting evidence that should prompt a reassessment of high-dose IV vitamin C protocols currently used in burn units worldwide.