Journal Article

Early administration of vitamin C in patients with sepsis or septic shock in emergency departments: a multicenter, double-blind, randomized controlled trial: the C-EASIE trial

Vanhove, Philippe, Vandervelden, Stefanie, Desruelles, Didier, Monsieurs, Koen, Fieuws, Steffen, Hubloue, Ives, Eegdeman, Wilma, Creteur, Jacques, Breuls, Jan, Cortens, Bente, Wauters, Lina, Stifkens, François, Malinverni, Stefano

2025

Overview

Background Sepsis and septic shock are associated with high mortality and morbidity despite adequate standard care. Vitamin C deficiency is a common, potentially reversible, contributor to morbidity and mortality in sepsis. Previous studies have shown mixed and conflicting results. Our study aimed to determine the potential benefit of early administration (within 6 h after admission) of vitamin C in patients with sepsis or septic shock. Methods This was a phase 3b prospective, multicenter, double-blinded, randomized placebo-controlled trial. Participants were enrolled in the Emergency Departments of 8 hospitals throughout Belgium. Patients were randomized to receive 1.5 g of vitamin C, or matching placebo, every 6 h for 4 days. The primary outcome was the average post-baseline patient Sequential Organ Failure Assessment (SOFA) score on day 2 to 5. Key secondary outcomes were the maximum SOFA score, 28-day mortality and length of ICU and hospital stay. Results A total of 300 patients were recruited between June 4th, 2021, and August 19th, 2023. 292 patients, of which 147 were assigned to the vitamin C and 145 to the placebo group, completed the trial and were included in the analysis. The primary outcome (vitamin C, 1.98; placebo, 2.19) was 8.7% lower in the vitamin C group, but not significantly (ratio 0.91, 95% CI 0.77 to 1.08, P  = 0.30). In a planned subgroup analysis, patients with a baseline SOFA score of 6 or above had a significant lower average post-baseline SOFA score in the vitamin C group (ratio 0.76, 95% CI 0.86 to 0.99, P  = 0.042). Findings were similar in the two groups regarding secondary outcomes and adverse events, except for a lower probability of being on renal replacement therapy in the vitamin C group of the per protocol analysis (ratio 0.28, 95% CI 0.078 to 1.0, P  = 0.05). Conclusions Early treatment with vitamin C did not result in a statistically significant reduction in organ dysfunction. Therefore, this study does not support the use of vitamin C in sepsis patients. Trial registration : ClinicalTrials.gov Identifier: NCT04747795 . Registered 4 February 2021. Key Points Question Does early treatment with vitamin C lead to a less severe disease course in patients with sepsis or septic shock? Findings In this randomized clinical trial that included 292 patients, treatment with intravenous vitamin C compared to placebo did not result in a lower average post-baseline patient Sequential Organ Failure Assessment (SOFA) score on day 2 to 5 (1.98 vs 2.19), except for a subgroup of patients with a baseline SOFA score of 6 or above. Meaning Early treatment with vitamin C did not result in a significant improvement of the disease course.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: Aged / Antibiotics / Ascorbic Acid - administration & dosage / Ascorbic Acid - pharmacology / Ascorbic Acid - therapeutic use / Belgium / Clinical trials / Consent / Critical Care Medicine / Double-Blind Method / Emergency medical care / Emergency Medicine / Emergency service / Emergency Service, Hospital - organization & administration / Emergency Service, Hospital - statistics & numerical data / Evidence / Female / Health aspects / Hospitals / Humans / Infection / Infections / Intensive / Intensive Care Units - organization & administration / Intensive Care Units - statistics & numerical data / Male / Medicine / Medicine & Public Health / Middle Aged / Mortality / Organ Dysfunction Scores / Patients / Product development / Prospective Studies / Questionnaires / Sepsis / Sepsis - drug therapy / Septic shock / Shock, Septic - drug therapy / Statistical analysis / Vitamin C / Vitamins - administration & dosage / Vitamins - therapeutic use