High-dose IV vitamin C in severe burns was stopped for harm

Design

Phase 3, randomised, double-blind, placebo-controlled, stopped early (VICTORY)

Population

238 adults with ≥20% TBSA deep burns requiring grafting, 24 centres

Primary outcome

28-day death or persistent organ dysfunction (ventilation, KRT, vasopressors)

Effect

40.8% vs 29.7%, RR 1.28 (0.99–1.65); 28-day mortality 15.0% vs 7.6%, RR 1.96 (1.32–2.90)

VICTORY was a double-blind, placebo-controlled phase 3 trial at 24 burn centres across the Americas, Europe and Asia. Adults with deep burns covering at least 20% of body surface area were randomised to IV vitamin C 50 mg/kg every 6 hours for 96 hours or placebo. It stopped early at the first interim analysis after 238 patients.

Death or persistent organ dysfunction at 28 days — dependence on ventilation, kidney replacement therapy or vasopressors — occurred in 40.8% with vitamin C and 29.7% with placebo (adjusted RR 1.28, 95% CI 0.99–1.65). Twenty-eight-day mortality was 15.0% versus 7.6% (RR 1.96, 1.32–2.90), and hospital mortality 23.3% versus 16.1%.

High-dose vitamin C has been used in burn resuscitation to reduce capillary leak, and in sepsis. This trial suggests possible harm. Megadose vitamin C also causes oxalate nephropathy and falsely raises point-of-care glucose readings — both reasons for nephrologists to question it in ICU patients.

• Do not use high-dose IV vitamin C in severe burns outside trials.
• Remember that megadose vitamin C can cause oxalate nephropathy and acute kidney injury.
• Point-of-care glucometers may read falsely high with IV vitamin C — confirm with a laboratory glucose.
• Ask about vitamin C infusions in ICU patients with unexplained AKI.

Why it matters

It reverses a plausible, widely tried adjunct, with a mortality signal that cannot be ignored.

Don't overread it

The primary composite narrowly missed significance; the mortality difference is a secondary outcome in a trial stopped early.

The statistics, in plain English

Trials stopped early tend to exaggerate effects, but a doubling of 28-day mortality with an interval from 1.32 to 2.90 is a strong enough harm signal to stop using the drug.

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