High-Dose Intravenous Vitamin C and Mortality and Organ Dysfunction in Severe Burn Injury: The VICTORY Randomized Clinical Trial.

Summary

In a 24-center, double-blind phase 3 RCT of 238 adults with severe burns, high-dose IV vitamin C failed to reduce the composite of 28-day mortality or persistent organ dysfunction and showed higher 28-day and hospital mortality versus placebo. The trial was stopped early for futility/harm at the first interim analysis.

Key Findings

• Primary composite (28-day mortality or persistent organ dysfunction) occurred in 40.8% (vitamin C) vs 29.7% (placebo); adjusted RR 1.28 (95% CI 0.99–1.65), P=.06; crossed futility/harm boundary.
• 28-day mortality was higher with vitamin C: 15.0% vs 7.6%; adjusted RR 1.96 (95% CI 1.32–2.90), P=.001.
• Hospital mortality was higher with vitamin C: 23.3% vs 16.1%; adjusted RR 1.44 (95% CI 1.03–2.00), P=.03.
• No improvement in time to discharge alive within 90 days (subdistribution HR 0.85, 95% CI 0.62–1.16).

Clinical Implications

Clinicians should avoid prescribing high-dose IV vitamin C for severe burn injury outside of trials and revisit any protocols that include it, prioritizing evidence-based resuscitation and organ support strategies.

Limitations

• Early termination may limit precision and subgroup analyses
• Heterogeneity in burn severity and potential timing/dose-response uncertainties

Future Directions

Reassess antioxidant strategies in burn care; explore mechanistic pathways of harm, optimal dosing windows (if any), and patient phenotypes; prioritize robust pragmatic trials of supportive interventions.