Christian Stoppe, Aileen Hill, Leopoldo C. Cancio, A Day, Kaitlin A Pruskowski, Alexis F. Turgeon, Tam Pham, Sylvain Bélisle, Mario Aurelio Martínez‐Jiménez, Ulrich Limper, Jochen Gille, Jon Wisler, Alisa Savetamal, Jonathan Pollack, Daisy Grau Domínguez, Serge Jennes, Jeffrey W. Shupp, Marc G. Jeschke, K. Colpaert, Gabriel Hundeshagen, Justus P. Beier, Pornprom Muangman, Ann Echeverri McCandless, P M Meybohm, Tilman Grune, Ellen Dresen, Daniela Weber, Carina Güttler, Charles Chin Han Lew, Xuran Jiang, Shawna Froese, Maureen Dansereau, Zheng‐Yii Lee, D Heyland, VICTORY Study Team, Lucy Wibbenmeyer, Jack Rasmussen, John Harvin, Nicholas Meyer, Kevin Foster, Han Ting Wang, Michaël Chassé, Emmanuel Charbonney, Christopher Kolan, Martin Girard, François-Martin Carrier, Antoine Halwagh, Nicholas Robillard, Chloé Vo, Mélissa Gagnon-Hamelin, Andréa Gagnon-Hamelin, Fransesca Lamothe, Cindy Prié, François Lauzier, Charles Langis Francoeur, Guillaume Leblanc, Maude St. Onge, Éric Brassard, Simon Demers-Marcil, Tuong-Vi Tran, Olivier Costerhousse, David Bellemare, Stéphanie Massana, Eve Cloutier, Stéphanie Nadeau-Caplette, Juan Manuel Shiguetomi-Medina, Julián Rosendo Ávila-Delgadillo, Diana Estefanía Campos-López, Patricia Aurea Cervantes-Báez, María Isabel Patiño-López, Barclay Stewart, Saman Arbabi, Jamie Oh, Dylan Jason, Alex Morzycki, April Cowgill, Joong Kim, Bao-Chau Vo, My-Trang Robinson, Carrie Yuan, Emily Eschelbach, David Crawford, Jerome Defosse, S. Trojan, Steffen Knigge, Cornelia Schweiger, Katharina Nissen, Hannah Jopp, Sarah Bennecke, Shaymaa Al-Dabooni, Karsten Jahn, Armin Sablotzki, Anke Brandt, Heike Liebetrau, Ulrike Schmidt, Elisabeth Schmidt, Birgit Labitzke, Christiane Germander, Marie Ullbrich, John Loftus
Importance: Severe burn injury triggers systemic inflammation that can lead to multiple organ dysfunctions and death. High-dose intravenous vitamin C has been proposed to mitigate these effects, but strong evidence in patients with burn injury is lacking. Objective: To evaluate the efficacy of high-dose intravenous vitamin C in patients with severe burn injury. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled phase 3 trial conducted across 24 burn centers in North, Central, and South America; Europe; and Asia. Adults (≥18 years) with deep second- and/or third-degree burns covering 20% or more of total body surface area and requiring skin grafting were enrolled between August 18, 2020, and September 12, 2025. Final follow-up was completed in March 2026. The trial was stopped early after the first prespecified interim analysis for futility/harm. Interventions: Patients were randomly assigned (1:1) to receive intravenous vitamin C (50 mg/kg every 6 hours for 96 hours) or matched placebo. Main Outcomes and Measures: The primary outcome was a composite of 28-day mortality and persistent organ dysfunction (defined as dependence on mechanical ventilation, kidney replacement therapy, or vasopressor/inotrope support at day 28). The main secondary outcome was time to discharge alive from hospital within 90 days. Results: Among 238 patients enrolled (mean age, 48.9 [SD, 19.1] years; 79% male; mean total body surface area, 37.0% [SD, 14.6%]), 120 were assigned to vitamin C and 118 to placebo. The primary composite outcome occurred in 49 patients (40.8%) in the vitamin C group and 35 patients (29.7%) in the placebo group (adjusted risk ratio [RR], 1.28 [95% CI, 0.99-1.65]; P = .06), crossing the prespecified futility/harm threshold and prompting early trial termination. Time to discharge alive from hospital within 90 days was not improved (adjusted subdistribution hazard ratio, 0.85 [95% CI, 0.62-1.16]; P = .31). Twenty-eight-day mortality was higher in the vitamin C group (15.0% vs 7.6%; adjusted RR, 1.96 [95% CI, 1.32-2.90]; P = .001), as was hospital mortality (23.3% vs 16.1%; adjusted RR, 1.44 [95% CI, 1.03-2.00]; P = .03). Conclusions and Relevance: Among patients with severe burn injury, high-dose intravenous vitamin C did not reduce 28-day mortality and persistent organ dysfunction and is possibly harmful. Trial Registration: ClinicalTrials.gov Identifier: NCT04138394.