Effect of an Herbal-Based Injection on 28-Day Mortality in Patients With Sepsis: The EXIT-SEP Randomized Clinical Trial.

Importance: Previous research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis. Objective: To determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis. Design, Setting, and Participants: The Efficacy of Xuebijing Injection in Patients With Sepsis (EXIT-SEP) trial was a multicenter, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites and included 1817 randomized patients with sepsis (sepsis 3.0) present for less than 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled. The study was conducted from October 2017 to June 2019. The final date of follow-up was July 26, 2019. Data analysis was performed from January 2020 to August 2022. Interventions: The patients were randomized to receive either intravenous infusion of XBJ (100 mL, n = 911) or volume-matched saline placebo (n = 906) every 12 hours for 5 days. Main Outcomes and Measures: The primary outcome was 28-day mortality. Results: Among the 1817 patients who were randomized (mean [SD] age, 56.5 [13.5] years; 1199 [66.0%] men), 1760 (96.9%) completed the trial. In these patients, the 28-day mortality rate was significantly different between the placebo group and the XBJ group (230 of 882 patients [26.1%] vs 165 of 878 patients [18.8%], respectively; P < .001). The absolute risk difference was 7.3 (95% CI, 3.4-11.2) percentage points. The incidence of adverse events was 222 of 878 patients (25.3%) in the placebo group and 200 of 872 patients (22.9%) in the XBJ group. Conclusions and Relevance: In this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03238742.

The clinical outcomes of selenium supplementation on critically ill patients: A meta-analysis of randomized controlled trials.

PURPOSE: Selenium supplementation is a potentially promising adjunctive therapy for critically ill patients, but the results are controversy among studies. Accordingly, we performed this meta-analysis to more clearly detect the efficacy and safety of selenium supplementation on critically ill patients. METHODS: Systematic literature retrieval was carried out to obtain RCTs on selenium supplementation for critically ill patients up to August 2017. Data extraction and quality evaluation of these studies were performed by 2 investigators. Statistical analyses was performed by RevMan 5.3. Trial sequential analysis (TSA) was conducted to control the risks of type I and type II errors and calculate required information size (RIS). RESULTS: Totally 19 RCTs involving 3341 critically ill patients were carried out in which 1694 participates were in the selenium supplementation group, and 1647 in the control. The aggregated results suggested that compared with the control, intravenous selenium supplement as a single therapy could decrease the total mortality (RR = 0.86, 95% CI: 0.78-0.95, P = .002, TSA-adjusted 95% CI = 0.77-0.96, RIS = 4108, n = 3297) and may shorten the length of stay in hospital (MD -2.30, 95% CI -4.03 to -0.57, P = .009), but had no significant treatment effect on 28-days mortality (RR = 0.96, 95% CI: 0.85-1.09, P = .54) and could not shorten the length of ICU stay (MD -0.15, 95% CI -1.68 to 1.38, P = .84) in critically ill patients. Our results also showed that selenium supplementation did not increase incidence of drug-induced side effect compared with the control (RR 1.04, 95% CI 0.83 to 1.30, P = .73). CONCLUSIONS: The current evidence suggests that the use of selenium could reduce the total mortality, and TSA results showed that our outcome is reliable and no more randomized controlled trials are needed. But selenium supplementation might have no effect on reducing 28-days mortality as well as the incidence of new infections, or on length of stay in ICU or mechanical ventilation. However, the results should be used carefully because of potential limitations.