{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T09:56:30Z","timestamp":1793094990979,"version":"4.5.0"},"reference-count":28,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"\n Importance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the efficacy of high-dose intravenous vitamin C in patients with severe burn injury.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n Randomized, double-blind, placebo-controlled phase 3 trial conducted across 24 burn centers in North, Central, and South America; Europe; and Asia. Adults (\u226518 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.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Patients were randomly assigned (1:1) to receive intravenous vitamin C (50 mg\/kg every 6 hours for 96 hours) or matched placebo.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n 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];\n P<\/jats:italic>\n \u2009=\u2009.06), 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];\n P<\/jats:italic>\n \u2009=\u2009.31). Twenty-eight\u2013day mortality was higher in the vitamin C group (15.0% vs 7.6%; adjusted RR, 1.96 [95% CI, 1.32-2.90];\n P<\/jats:italic>\n \u2009=\u2009.001), as was hospital mortality (23.3% vs 16.1%; adjusted RR, 1.44 [95% CI, 1.03-2.00];\n P<\/jats:italic>\n \u2009=\u2009.03).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT04138394<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jama.2026.10616","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T13:30:20Z","timestamp":1781098220000},"page":"929","source":"Crossref","is-referenced-by-count":7,"title":["High-Dose Intravenous Vitamin C and Mortality and Organ Dysfunction in Severe Burn Injury"],"prefix":"10.1001","volume":"336","author":[{"given":"Christian","family":"Stoppe","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"Department of Cardiac Anesthesiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, Berlin, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), Berlin, Germany"},{"name":"Center for Outcomes Research, UTHealth, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aileen","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, University Hospital RWTH, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leopoldo C.","family":"Cancio","sequence":"additional","affiliation":[{"name":"US Army Institute of Surgical Research Burn Center, JBSA Fort Sam Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G.","family":"Day","sequence":"additional","affiliation":[{"name":"Kingston Health Sciences Centre\u2014Research Institute, Kingston, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin A.","family":"Pruskowski","sequence":"additional","affiliation":[{"name":"US Army Institute of Surgical Research Burn Center, JBSA Fort Sam Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis F.","family":"Turgeon","sequence":"additional","affiliation":[{"name":"Population Health and Optimal Health Practices Research Unit (Trauma-Emergency-Critical Care Medicine), CHU de Qu\u00e9bec\u2014Universit\u00e9 Laval Research Center, Qu\u00e9bec City, Qu\u00e9bec, Canada"},{"name":"Division of Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, 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