Sepsis and septic shock represent critical conditions frequently encountered in emergency medicine, carrying significant risks of morbidity and mortality. Vitamin C has been proposed as a potential therapeutic agent due to its antioxidant, anti-inflammatory, and immunomodulatory properties.
The C-EASIE trial was conducted to evaluate whether early intravenous administration of vitamin C in patients presenting with sepsis or septic shock could reduce organ dysfunction and improve clinical outcomes. The trial was conducted across eight emergency departments in Belgium. Adult patients meeting Sepsis-3 criteria, requiring intravenous antibiotics and fluids, were enrolled within six hours of presentation. Participants were randomised to receive either intravenous vitamin C (1.5 grams every six hours for four days) or a matching placebo. The primary outcome was the average Sequential Organ Failure Assessment (SOFA) score from days 2 to 5 post-enrollment. Secondary outcomes included the maximum SOFA score, 28-day mortality, need for renal replacement therapy, and length of ICU and hospital stay.
Between June 2021 and August 2023, a total of 300 patients were enrolled; 292 patients completed the study protocol (147 in the vitamin C group and 145 in the placebo group). Baseline characteristics, including demographics and initial severity of illness (mean baseline SOFA score approximately 5.9), were comparable between groups. Approximately two-thirds of patients presented with septic shock.
The primary analysis demonstrated no statistically significant difference in the mean post-baseline SOFA score between groups. The vitamin C group had an average SOFA score of 1.98 compared to 2.19 in the placebo group. Thus, early vitamin C administration did not significantly reduce organ dysfunction among the general cohort of patients with sepsis or septic shock.
Subgroup analyses, however, suggested a potential benefit in patients with higher severity of illness. In patients with a baseline SOFA score of six or greater, vitamin C administration was associated with a significantly lower average post-baseline SOFA score compared to placebo. This finding indicates that patients with more pronounced organ dysfunction at presentation may derive greater benefit from vitamin C therapy, although the trial was not powered to definitively confirm subgroup effects.
Regarding secondary outcomes, no significant differences were observed between groups. Maximum SOFA scores, 28-day mortality rates (18.4% in the vitamin C group versus 20.0% in the placebo group), and durations of ICU and hospital stays were similar. A notable observation emerged in the per-protocol analysis: patients who received at least 75% of the scheduled vitamin C doses exhibited a lower probability of requiring renal replacement therapy compared to those receiving placebo. This suggests a possible renal protective effect of vitamin C, although the result should be interpreted cautiously given the risk of type I error due to multiple comparisons.
The trial also confirmed the safety of intravenous vitamin C at the studied doses. The incidence of adverse events, including electrolyte disturbances and hypoglycaemia, was low and comparable between groups. No new safety concerns were identified.
In conclusion, the C-EASIE trial did not find evidence that early administration of intravenous vitamin C significantly reduces organ dysfunction in patients with sepsis or septic shock overall. Nonetheless, exploratory subgroup analyses suggest that vitamin C may offer benefit in patients presenting with more severe illness, and it may reduce the need for renal replacement therapy among those receiving complete dosing schedules. These findings do not support the routine use of vitamin C for all patients with sepsis but highlight the potential for benefit in specific subgroups. Further research is warranted to explore these possibilities and to refine patient selection for vitamin C-based interventions in sepsis management.
Source: Critical Care
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