Publication

• Title: High-Dose Intravenous Vitamin C and Mortality and Organ Dysfunction in Severe Burn Injury: The VICTORY Randomized Clinical Trial
• Acronym: VICTORY / VICToRY
• Year: 2026
• Journal published in: JAMA
• Citation: 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 June 10, 2026.

Context & Rationale

• Background

  • Severe burn injury produces an early systemic inflammatory and oxidative response, endothelial injury, capillary leak, shock, oedema, hypermetabolism, infection risk, organ dysfunction, and death.
  • Vitamin C was biologically attractive because it can scavenge reactive oxygen species, support endothelial barrier function, influence vasopressor biology, and potentially support wound healing.
  • High-dose intravenous vitamin C had been used in burn shock resuscitation mainly to reduce fluid requirements, based on small trials, observational studies, and physiological rationale.
  • The accompanying editorial emphasised that high-dose vitamin C in burns had moved from a plausible antioxidant hypothesis to a persistent clinical practice despite limited patient-centred outcome evidence. ¹
  • The early Tanaka trial reported reduced resuscitation fluid volume using a higher continuous vitamin C infusion regimen, but subsequent work raised doubts about sustained fluid benefit and possible kidney harm. ²³⁴
  • In sepsis and general critical illness, the signal had become less favourable: LOVIT used the same 50 mg/kg every 6 hours for 96 hours regimen and found increased death or persistent organ dysfunction in septic shock. ⁵
  • Meta-analyses before VICTORY remained vulnerable to trial size, risk of bias, heterogeneity, and subgroup effects, especially the distinction between vitamin C monotherapy and combined hydrocortisone-thiamine-vitamin C strategies. ⁶⁷
• Research Question/Hypothesis

  • The trial tested whether early high-dose intravenous vitamin C would reduce the composite of 28-day mortality and persistent organ dysfunction in adults with severe burn injury.
  • The central hypothesis was that supraphysiological vitamin C, given during the acute oxidative and capillary-leak phase, would improve organ function and survival.
  • The main secondary hypothesis was that vitamin C would accelerate discharge alive from hospital within 90 days.
• Why This Matters

  • Severe burns are high-cost, high-morbidity critical illness events with prolonged ICU and hospital trajectories.
  • Vitamin C is inexpensive and widely available, so a true benefit would be rapidly scalable internationally.
  • A harm signal would also be practice-changing because high-dose vitamin C had been perceived by many clinicians as biologically plausible and relatively safe.
  • VICTORY directly addressed whether high-dose vitamin C should be used as pharmaconutrition in severe burns, rather than as ordinary micronutrient replacement.

Design & Methods

• Research Question:
  • In adults with severe burn injury, does early high-dose intravenous vitamin C, compared with matched placebo, reduce 28-day mortality or persistent organ dysfunction?
• Study Type:
  • International, multicentre, parallel-group, randomised, double-blind, placebo-controlled, phase 3 trial.
  • Conducted in 24 burn centres across North, Central, and South America, Europe, and Asia.
  • Centrally coordinated by the Clinical Evaluation Research Unit at Queen’s University, Canada, with independent data and safety monitoring.
  • Randomisation used a secure web-based system with permuted blocks of 2, 4, and 6, stratified by clinical centre; the unblinded site pharmacist prepared the assigned study product while other personnel remained blinded. ⁸
• Population:
  • Adults aged ≥18 years.
  • Deep second- and/or third-degree burns.
  • Burns covering ≥20% total body surface area.
  • Expected to require skin grafting, assessed by the attending burn surgeon.
  • Enrolled early after injury: patients presenting beyond the prespecified 24-hour window were excluded.
  • Key exclusions included moribund state with expected death within 72 hours, pregnancy or lactation, current high-dose intravenous vitamin C, known glucose-6-phosphate dehydrogenase deficiency, recent kidney stones, concurrent hydroxocobalamin for suspected cyanide poisoning, another industry-sponsored ICU interventional trial, and selected Germany-specific haematological or hypersensitivity exclusions. ⁸
• Intervention:
  • Intravenous vitamin C at 50 mg/kg pre-burn body weight every 6 hours for 96 hours.
  • Dosing weight was capped at 150 kg.
  • The maximum daily dose was therefore 200 mg/kg/day, capped at 30 g/day.
  • The infusion rate did not exceed 100 mg/min.
  • Vitamin C was diluted in 0.9% sodium chloride or 5% dextrose to a final concentration of 1 to 25 mg/mL, protected from light, and prepared by local research pharmacies. ⁸
• Comparison:
  • Matched placebo with identical volume and administration schedule.
  • Placebo consisted of 5% dextrose in water or 0.9% sodium chloride according to site practice.
  • Open-label intravenous vitamin C for ordinary nutrient repletion was permitted up to 200 mg/day.
  • Fluid resuscitation followed local burn-centre protocols; no trial-mandated fluid protocol was imposed.
  • Most sites used crystalloid-based resuscitation guided by modified Brooke-style formulae or local adaptations, with colloids and blood products at treating clinician discretion.
• Blinding:
  • Double-blind.
  • Patients, clinicians, investigators, trial staff, and outcome assessors remained unaware of treatment assignment.
  • Only the site pharmacist preparing the study product was unblinded.
  • Blinding was a major strength because vitamin C had strong pre-existing clinician beliefs and because fluid and organ-support decisions could otherwise be vulnerable to performance bias.
• Statistics:
  • A total of 333 patients per group was planned to detect a reduction in 28-day persistent organ dysfunction or death from 27% to 18% with 78% power at a two-sided alpha of 0.05, allowing two interim analyses for futility and harm.
  • The same sample size was estimated to provide 90% power to detect a subdistribution hazard ratio of 1.32 for time to discharge alive, assuming 10% hospital mortality in both groups and 5% loss to follow-up. ⁸
  • The primary analysis followed the intention-to-treat principle with no post-randomisation exclusions.
  • The primary outcome was analysed using modified Poisson regression with robust standard errors clustered by site, adjusted for age, total body surface area burned, baseline mechanical ventilation, and site.
  • The main secondary outcome, time to discharge alive, was analysed using a competing-risks Fine and Gray model, treating death as a competing event.
  • Two interim analyses were planned after approximately 33% and 66% of patients had 28-day outcome data; an adjusted RR greater than 1.1 favouring control triggered consideration of early termination for futility/harm.
• Follow-Up Period:
  • Primary outcome: 28 days after randomisation.
  • Main secondary outcome: discharge alive from hospital within 90 days.
  • Tertiary and longer-term outcomes included ICU and hospital outcomes, 6-month mortality, health-related quality of life, and activities of daily living.
  • Final follow-up was completed in March 2026.

Key Results

This trial was stopped early after the first prespecified interim analysis because the primary outcome crossed the futility/harm threshold favouring placebo. The planned sample size was 666 patients, but 238 were randomised: 120 to vitamin C and 118 to placebo.

• There was no subgroup suggesting benefit for the primary outcome: age ≥47 years RR 1.3 (95% CI 0.9 to 1.8), age <47 years RR 1.5 (95% CI 0.9 to 2.5), TBSA ≥33% RR 1.5 (95% CI 1.0 to 2.1), TBSA <33% RR 1.1 (95% CI 0.7 to 1.9), intervention start ≥14.6 hours RR 1.5 (95% CI 0.9 to 2.4), and intervention start <14.6 hours RR 1.1 (95% CI 0.8 to 1.7); all interaction P values were >.05. ⁸
• For time to discharge alive, subgroup HRs were consistently ≤1, not favouring vitamin C: TBSA ≥33% HR 0.6 (95% CI 0.4 to 1.1), TBSA <33% HR 0.9 (95% CI 0.6 to 1.3), and both early and later treatment-start subgroups HR 0.9 with wide confidence intervals.
• The central result is therefore not “failed fluid-sparing physiology”; it is absence of patient-centred benefit plus a coherent mortality and organ-support safety concern.

Internal Validity

• Randomisation and Allocation:
  • Allocation concealment was strong: central secure web-based randomisation, permuted blocks, stratification by site, and preparation by an unblinded pharmacist separated from clinical care.
  • All 238 randomised patients received the allocated study product and were included in the primary analysis.
  • No post-randomisation exclusions were applied to the main analyses.
• Dropout and Exclusions:
  • Of 685 adults assessed, 354 were eligible, 276 were approached for consent, and 238 were randomised.
  • Major pre-randomisation exclusions were more than 24 hours from admission to participating hospital to consent (148), moribund status (117), admission to burn unit more than 24 hours after injury (55), hydroxocobalamin use (23), another industry-sponsored ICU trial (7), recent kidney stones (4), pregnancy or lactation (2), already receiving high-dose intravenous vitamin C (1), and known G6PD deficiency (1).
  • Seventy-eight eligible patients were not approached for consent, most commonly because next of kin or a substitute decision-maker was unavailable (39) or because of clinical-team recommendation (21).
  • Thirty-eight approached patients did not provide consent.
  • These exclusions affect external validity more than internal validity, because randomised patients had complete primary outcome inclusion.
• Performance and Detection Bias:
  • Double-blinding substantially reduced performance and detection bias.
  • The primary outcome combined mortality with objectively recorded ongoing mechanical ventilation, kidney replacement therapy, or vasopressor/inotrope support at day 28.
  • Organ-support endpoints can still be influenced by local burn ICU practice, thresholds for extubation, kidney replacement therapy, and goals-of-care decisions, but blinding makes differential bias less likely.
• Protocol Adherence:
  • Protocol adherence was high: 187/238 patients (78.6%) received all 16 doses within 96 hours.
  • All 16 doses were completed in 94/120 (78.3%) vitamin C patients and 93/118 (78.8%) placebo patients.
  • Among 51 patients who did not complete all doses, 40 died, were discharged, or withdrew consent during the treatment window.
  • Adherence to administered intravenous doses was 99.6% overall.
  • Protocol violation events occurred in 30 unique patients: 12 in the vitamin C group and 18 in the placebo group. ⁸
• Baseline Characteristics:
  • Groups were broadly balanced.
  • Mean age was 48.2 ± 18.4 years with vitamin C versus 49.5 ± 19.9 years with placebo.
  • Male sex was 95/120 (79.2%) versus 93/118 (78.8%).
  • Mean burn size was 37.4% ± 15.0% versus 36.5% ± 14.3% total body surface area.
  • Inhalation injury was present in 35/120 (29.2%) versus 34/118 (28.8%).
  • Mean SOFA score was 3.2 ± 2.3 versus 3.4 ± 2.5.
  • Mean APACHE II score was 16.2 ± 7.8 versus 15.5 ± 7.0 among patients with complete data.
  • Mechanical ventilation at randomisation was present in 70/120 (58.3%) versus 66/118 (55.9%).
• Heterogeneity:
  • Clinical heterogeneity was expected in an international burn trial, including differences in injury mechanism, burn size, inhalation injury, resuscitation practice, grafting strategies, and local burn ICU pathways.
  • The intervention effect was directionally consistent across age, SOFA score, APACHE II score, burn size, and timing subgroups.
  • Site-level outcome heterogeneity was substantial: 6-month mortality by site ranged from 0% to 57.1%. ⁸
  • Several sites enrolled small numbers of patients, which may have produced incomplete blocks and reduced precision.
• Timing:
  • The intervention was delivered during the intended early post-burn window.
  • Median time from injury to admission at the study hospital was 2.8 hours (IQR 1.2 to 5.8) in the vitamin C group and 3.3 hours (IQR 1.7 to 5.6) in placebo.
  • Median time from ICU admission to first study dose was 15.5 hours (IQR 6.4 to 21.1) versus 14.6 hours (IQR 7.3 to 20.5).
  • Mean time from randomisation to intervention start was 3.8 ± 3.7 hours versus 3.5 ± 3.7 hours.
  • Intervention start more than 24 hours after ICU admission occurred in 11/120 (9.2%) versus 12/118 (10.2%).
  • This timing was appropriate for testing early oxidative and capillary-leak biology, but less well aligned with prevention of burn sepsis that often occurs weeks later.
• Dose:
  • The tested dose was high-dose pharmaconutrition, not standard vitamin C replacement.
  • The regimen, 50 mg/kg every 6 hours for 96 hours, matched the LOVIT sepsis regimen and far exceeded routine micronutrient repletion.
  • The dose was biologically credible and operationally deliverable, but not identical to older continuous high-dose burn-resuscitation protocols such as 66 mg/kg/hour.
  • A different dosing schedule, longer treatment duration, or sepsis-proximate administration remains a separate hypothesis and was not tested.
• Separation of the Variable of Interest:
  • Study-drug delivery separated well: vitamin C patients received high-dose ascorbic acid and placebo patients received matched crystalloid/dextrose placebo.
  • Full-dose completion was nearly identical: 78.3% versus 78.8%.
  • Dose compliance was 99.3% ± 4.3% versus 99.9% ± 0.6%.
  • Open-label vitamin C exceeding permitted doses occurred only in placebo patients and was rare.
  • Fluid outcomes showed no beneficial separation: total ICU fluid in 5908.6 mL versus 5096.4 mL; total fluid balance 2728.9 mL versus 2557.0 mL.
• Key Delivery Aspects:
  • Study-product preparation was standardised despite the use of different locally available vitamin C formulations.
  • Local fluid resuscitation protocols were retained, strengthening pragmatic relevance.
  • The absence of a mandated fluid protocol makes fluid-balance interpretation less mechanistically clean.
  • Blood product and albumin use did not suggest major imbalance: blood products were administered in 66/120 (55.0%) versus 66/118 (55.9%), and any albumin in 79/120 (65.8%) versus 77/118 (65.3%). ⁸
• Crossover:
  • Clinically meaningful crossover was minimal.
  • Open-label intravenous vitamin C above 200 mg/day occurred in 1 placebo patient.
  • Oral vitamin C above 1500 mg/day occurred in 3 placebo patients.
  • This low level of contamination would not plausibly hide a major benefit of high-dose intravenous vitamin C.
• Adjunctive Therapy Use:
  • Burn-related procedures were frequent in both groups: 108/120 (90.0%) versus 101/118 (85.6%).
  • Autografting occurred in 65/120 (54.2%) versus 80/118 (67.8%).
  • Spray-on epithelial cells or cultured epithelial autograft were used in 22/120 (18.3%) versus 34/118 (28.8%).
  • These imbalances are post-randomisation and may reflect survival, operative trajectories, graft availability, or local practice rather than treatment assignment alone.
• Outcome Assessment:
  • The primary outcome was clearly defined and clinically meaningful.
  • Mortality is objective.
  • Persistent organ dysfunction at day 28 is clinically relevant but depends partly on organ-support thresholds and local practice.
  • Time to discharge alive appropriately handled death as a competing event.
  • Six-month health-related quality-of-life results were survivor-conditioned and should not be interpreted independently of the higher mortality in the vitamin C arm.
• Statistical Rigor:
  • The main analysis followed intention-to-treat with no post-randomisation exclusions.
  • The early stopping rule was prespecified and based on the primary composite outcome.
  • The trial was stopped at the first interim analysis, substantially reducing precision for treatment effects and rare harms.
  • The supplement documents several analytic changes: no per-protocol analysis was performed because compliance was high; age was added to adjusted analyses, while traumatic brain injury and injury severity score were removed; the 6-month quality-of-life analysis was not weighted by augmented inverse probability; and ClinicalTrials.gov had incorrectly listed time to discharge alive as a second primary outcome before correction in March 2026. ⁸
  • These deviations were transparently reported and mostly reasonable, but they reinforce that the mortality signal should be interpreted with attention to imprecision and early stopping.
• Conclusion on Internal Validity:
  • Overall, internal validity is strong for the question actually tested: early high-dose intravenous vitamin C versus placebo in adult severe burns.
  • The principal caveats are early termination, reduced sample size, sparse mortality events, site-level heterogeneity, and limited precision for uncommon harms.

External Validity

• Population Representativeness:
  • The trial population represented adults with major burns treated in specialist burn centres.
  • Mean age was 48.9 years and 79% were male.
  • Mean burn size was 37.0% total body surface area.
  • Approximately 57% required mechanical ventilation for at least 72 hours.
  • Patients were sick enough to have meaningful risk of organ dysfunction and death, but moribund patients expected to die within 72 hours were excluded.
  • The trial was geographically broad, including centres in the Americas, Europe, and Asia, improving generalisability beyond a single national burn system.
• Important Exclusions:
  • Children were not included.
  • Patients with burns <20% total body surface area were not included.
  • Late presenters beyond the enrolment window were excluded.
  • Patients receiving hydroxocobalamin for suspected cyanide poisoning were excluded.
  • Patients with known G6PD deficiency, recent kidney stones, pregnancy or lactation, or existing high-dose intravenous vitamin C exposure were excluded.
  • Moribund patients unlikely to survive 72 hours were excluded.
• Applicability:
  • The findings apply directly to routine early high-dose intravenous vitamin C at 50 mg/kg every 6 hours for 96 hours in adults with severe burns requiring grafting.
  • The findings do not address ordinary low-dose vitamin C replacement for deficiency or standard nutritional supplementation.
  • The findings do not address high-dose vitamin C given later, at the time of proven burn sepsis, or as part of a different targeted antioxidant protocol.
  • The findings should be highly relevant to modern burn centres using protocolised crystalloid-based resuscitation and contemporary organ-support practices.
  • Resource-limited burn systems may differ in time to presentation, grafting access, fluid protocols, infection epidemiology, and ICU availability, but the lack of benefit and possible harm argue against routine adoption in those settings.
• Conclusion on External Validity:
  • External validity is good for adult severe burn patients treated early in specialist burn centres.
  • Generalisability is limited for children, smaller burns, late presenters, cyanide-poisoning pathways requiring hydroxocobalamin, ordinary micronutrient replacement, and later sepsis-directed vitamin C therapy.

Strengths & Limitations

• Strengths:
  • Randomised, double-blind, placebo-controlled design.
  • International recruitment across 24 burn centres.
  • Complete primary analysis of all randomised patients.
  • High adherence and excellent separation of the intervention.
  • Prespecified stopping rule for futility/harm.
  • Clinically meaningful primary outcome combining mortality and persistent organ dysfunction.
  • Competing-risks analysis for discharge alive, appropriately accounting for death.
  • Detailed safety reporting, including kidney outcomes, hypoglycaemia, haemolysis, acid-base/electrolyte events, and serious adverse events.
  • Directly addressed an entrenched, biologically plausible but under-evidenced burn practice.
• Limitations:
  • Stopped early after 238 randomised patients rather than the planned 666.
  • Reduced power and precision for all outcomes, especially mortality, quality of life, and uncommon harms.
  • Early stopping can overestimate harm, although trial simulations suggested only small bias under the prespecified rule.
  • No mandated fluid resuscitation protocol, limiting mechanistic interpretation of fluid outcomes.
  • Several centres enrolled small numbers, increasing the possibility of centre-level imbalance and imprecision.
  • Not powered to detect rare complications such as oxalate nephropathy.
  • No clear mechanistic biomarker endpoint explained the mortality signal.
  • The regimen tested cannot exclude benefit from different dosing, different timing, or use closer to established sepsis onset.

Interpretation & Why It Matters

• Clinical practice

  Routine early high-dose intravenous vitamin C should not be used in adults with severe burn injury to reduce organ dysfunction, mortality, or length of stay.
• Mechanistic lesson

  The trial separates biochemical plausibility from clinical benefit: antioxidant and endothelial-protective rationale did not translate into improved organ-support or survival outcomes.
• Fluid resuscitation

  The trial did not reproduce a clinically useful fluid-sparing effect in contemporary burn care; total ICU fluid input was numerically higher with vitamin C, not lower.
• Safety

  The concerning pattern was not a single dramatic toxicity but a consistent direction of worse death and organ-support outcomes, with more KRT initiation and serious adverse events numerically in the vitamin C group.
• Research implication

  Future vitamin C studies in burns would need a narrower biological target, compelling mechanistic justification, and safeguards around kidney injury and redox biology; routine empiric early use is no longer defensible.

Controversies & Subsequent Evidence

• Early stopping and interpretation of harm:
  • Stopping after the first interim analysis preserved patient safety but reduced precision.
  • The prespecified rule was conservative for efficacy because there was no interim efficacy test; it triggered on adjusted RR >1.1 favouring control for persistent organ dysfunction or death.
  • Simulation work in the supplement estimated that, under the null, the RR>1.1 rule would stop 33.3% of trials at the first interim and 8% at the second, with expected RR 1.08 and 94% confidence interval coverage. ⁸
  • The observed mortality signal is clinically important but numerically sparse, and the primary table itself notes that the adjusted mortality model may be unreliable due to few events.
• Composite endpoint:
  • The primary endpoint was clinically relevant because it captured death and prolonged organ support, both central outcomes in severe burns.
  • Composite outcomes can obscure component-specific effects, but VICTORY reported the components transparently.
  • The concerning interpretation is strengthened because the mortality component, rather than only a softer organ-support component, moved in the same unfavourable direction.
• Why earlier burn studies differed:
  • Earlier burn studies were generally small, often single-centre, sometimes unblinded, and frequently focused on fluid volume rather than survival or organ dysfunction.
  • The editorial emphasised that high-dose vitamin C for initial burn resuscitation had already declined after doubts about sustained 48- to 72-hour fluid benefit and concern about kidney failure. ¹
  • Modern protocolised resuscitation may have reduced the room for any incremental fluid-sparing benefit.
• Timing controversy: early oxidative phase versus late burn sepsis:
  • VICTORY administered vitamin C in the first 96 hours after burn injury.
  • The editorial highlighted that burn sepsis is uncommon in the first few days and often occurs weeks or months later, because large burns require prolonged wound coverage and repeated grafting cycles. ¹
  • This weakens the sepsis-prevention rationale for a 96-hour early intervention, even though it remains appropriate for testing acute capillary leak and oxidative injury.
• Renal and redox biology:
  • Ascorbic acid can be metabolised to oxalate, creating concern for oxalate nephropathy in hypovolaemic or acidotic patients.
  • VICTORY reported no oxalate kidney stones, severe haemolysis, severe acid-base/electrolyte imbalance, or refractory hypoglycaemia.
  • KRT initiation was nevertheless numerically higher with vitamin C: 13/120 (10.8%) versus 7/118 (5.9%).
  • The absence of diagnosed oxalate stones does not exclude subclinical oxalate kidney injury.
• Alignment with sepsis vitamin C trials:
  • VICTORY aligns directionally with LOVIT, which used the same dosing regimen in septic shock and found increased death or persistent organ dysfunction. ⁵
  • Severe infection and critical illness meta-analyses before VICTORY were low-certainty and heterogeneous, with signals sensitive to risk of bias and vitamin C monotherapy versus combination therapy. ⁶⁷
  • Combination vitamin C, thiamine, and hydrocortisone strategies in sepsis did not improve major clinical outcomes in VICTAS, VITAMINS, and ACTS, reinforcing that plausible metabolic cocktails require outcome evidence before routine use. ⁹¹⁰¹¹
  • CITRIS-ALI, another high-dose vitamin C monotherapy trial, did not improve its primary organ-failure and biomarker endpoints, although secondary mortality findings generated debate. ¹²
• Guideline implications:
  • Recent burn shock resuscitation guidance and older burn nutrition recommendations preceded VICTORY and should be reinterpreted in light of this trial. ¹³¹⁴
  • The Surviving Sepsis After Burn Campaign underscores that burn sepsis differs from general sepsis and has distinctive timing, microbiology, and wound-source biology; VICTORY does not support early vitamin C as a preventive strategy for that problem. ¹⁵

Further Reading

• 2026Greenhalgh DG. High-dose vitamin C in burns: time to stop. JAMA. Published online June 10, 2026.
• 2024Cartotto R, Johnson LS, Savetamal A, et al. American Burn Association clinical practice guidelines on burn shock resuscitation. J Burn Care Res. 2024;45(3):565-589.
• 2023Greenhalgh DG, Hill DM, Burmeister DM, et al. Surviving Sepsis After Burn Campaign. Burns. 2023;49(7):1487-1524.
• 2023Lee ZY, Ortiz-Reyes L, Lew CCH, et al. Intravenous vitamin C monotherapy in critically ill patients: a systematic review and meta-analysis of randomised controlled trials with trial sequential analysis. Ann Intensive Care. 2023;13(1):14.
• 2022Lamontagne F, Masse MH, Menard J, et al; LOVIT Investigators and the Canadian Critical Care Trials Group. Intravenous vitamin C in adults with sepsis in the intensive care unit. N Engl J Med. 2022;386(25):2387-2398.
• 2022Agarwal A, Basmaji J, Fernando SM, et al. Parenteral vitamin C in patients with severe infection: a systematic review. NEJM Evid. 2022;1(9):EVIDoa2200105.
• 2022Flores E, Sánchez-Sánchez M, Gutierrez C, et al. High dose ascorbic acid during acute resuscitation in critically burn patients. J Burn Care Res. 2022;43(1):149-155.
• 2021Sevransky JE, Rothman RE, Hager DN, et al; VICTAS Investigators. Effect of vitamin C, thiamine, and hydrocortisone on ventilator- and vasopressor-free days in patients with sepsis: the VICTAS randomized clinical trial. JAMA. 2021;325(8):742-750.
• 2020Fujii T, Luethi N, Young PJ, et al; VITAMINS Trial Investigators. Effect of vitamin C, hydrocortisone, and thiamine vs hydrocortisone alone on time alive and free of vasopressor support among patients with septic shock: the VITAMINS randomized clinical trial. JAMA. 2020;323(5):423-431.
• 2020Moskowitz A, Huang DT, Hou PC, et al; ACTS Clinical Trial Investigators. Effect of ascorbic acid, corticosteroids, and thiamine on organ injury in septic shock: the ACTS randomized clinical trial. JAMA. 2020;324(7):642-650.
• 2019Fowler AA III, Truwit JD, Hite RD, et al. Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure: the CITRIS-ALI randomized clinical trial. JAMA. 2019;322(13):1261-1270.
• 2018Lin J, Falwell S, Greenhalgh D, Palmieri T, Sen S. High-dose ascorbic acid for burn shock resuscitation may not improve outcomes. J Burn Care Res. 2018;39(5):708-712.
• 2013Rousseau AF, Losser MR, Ichai C, Berger MM. ESPEN endorsed recommendations: nutritional therapy in major burns. Clin Nutr. 2013;32(4):497-502.
• 2000Tanaka H, Matsuda T, Miyagantani Y, Yukioka T, Matsuda H, Shimazaki S. Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study. Arch Surg. 2000;135(3):326-331.

Summary

• VICTORY randomised 238 adults with severe burns to high-dose intravenous vitamin C, 50 mg/kg every 6 hours for 96 hours, or matched placebo.
• The trial was stopped early after the first interim analysis because the primary outcome crossed the prespecified futility/harm threshold.
• The primary composite of 28-day mortality or persistent organ dysfunction occurred in 40.8% with vitamin C versus 29.7% with placebo; adjusted RR 1.28; 95% CI 0.99 to 1.65; P=.06.
• Mortality was higher with vitamin C at 28 days and in hospital: 15.0% versus 7.6% at 28 days, and 23.3% versus 16.1% in hospital.
• Vitamin C did not improve discharge alive, ventilation duration, fluid balance, gram-negative bacteraemia, or 6-month outcomes.

Overall Takeaway

VICTORY is a practice-shaping severe-burn trial because it tests a long-standing, biologically plausible intervention with rigorous randomised evidence and finds no patient-centred benefit. Early high-dose intravenous vitamin C should not be used routinely after major burn injury; the burden of proof now lies with any narrower, biologically targeted vitamin C strategy.

Bibliography

• 1.Greenhalgh DG. High-dose vitamin C in burns: time to stop. JAMA. Published online June 10, 2026.
• 2.Tanaka H, Matsuda T, Miyagantani Y, Yukioka T, Matsuda H, Shimazaki S. Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study. Arch Surg. 2000;135(3):326-331.
• 3.Lin J, Falwell S, Greenhalgh D, Palmieri T, Sen S. High-dose ascorbic acid for burn shock resuscitation may not improve outcomes. J Burn Care Res. 2018;39(5):708-712.
• 4.Flores E, Sánchez-Sánchez M, Gutierrez C, et al. High dose ascorbic acid during acute resuscitation in critically burn patients. J Burn Care Res. 2022;43(1):149-155.
• 5.Lamontagne F, Masse MH, Menard J, et al; LOVIT Investigators and the Canadian Critical Care Trials Group. Intravenous vitamin C in adults with sepsis in the intensive care unit. N Engl J Med. 2022;386(25):2387-2398.
• 6.Lee ZY, Ortiz-Reyes L, Lew CCH, et al. Intravenous vitamin C monotherapy in critically ill patients: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis. Ann Intensive Care. 2023;13(1):14.
• 7.Agarwal A, Basmaji J, Fernando SM, et al. Parenteral vitamin C in patients with severe infection: a systematic review. NEJM Evid. 2022;1(9):EVIDoa2200105.
• 8.Stoppe C, Hill A, Cancio LC, et al; VICTORY Study Team. Supplemental online content to: high-dose intravenous vitamin C and mortality and organ dysfunction in severe burn injury: the VICTORY randomized clinical trial. JAMA. Published online June 10, 2026.
• 9.Sevransky JE, Rothman RE, Hager DN, et al; VICTAS Investigators. Effect of vitamin C, thiamine, and hydrocortisone on ventilator- and vasopressor-free days in patients with sepsis: the VICTAS randomized clinical trial. JAMA. 2021;325(8):742-750.
• 10.Fujii T, Luethi N, Young PJ, et al; VITAMINS Trial Investigators. Effect of vitamin C, hydrocortisone, and thiamine vs hydrocortisone alone on time alive and free of vasopressor support among patients with septic shock: the VITAMINS randomized clinical trial. JAMA. 2020;323(5):423-431.
• 11.Moskowitz A, Huang DT, Hou PC, et al; ACTS Clinical Trial Investigators. Effect of ascorbic acid, corticosteroids, and thiamine on organ injury in septic shock: the ACTS randomized clinical trial. JAMA. 2020;324(7):642-650.
• 12.Fowler AA III, Truwit JD, Hite RD, et al. Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure: the CITRIS-ALI randomized clinical trial. JAMA. 2019;322(13):1261-1270.
• 13.Cartotto R, Johnson LS, Savetamal A, et al. American Burn Association clinical practice guidelines on burn shock resuscitation. J Burn Care Res. 2024;45(3):565-589.
• 14.Rousseau AF, Losser MR, Ichai C, Berger MM. ESPEN endorsed recommendations: nutritional therapy in major burns. Clin Nutr. 2013;32(4):497-502.
• 15.Greenhalgh DG, Hill DM, Burmeister DM, et al. Surviving Sepsis After Burn Campaign. Burns. 2023;49(7):1487-1524.