Effect of an Herbal-Based Injection on 28-Day Mortality in Patients With Sepsis

Abstract

ImportancePrevious research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis.ObjectiveTo determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis.Design, Setting, and ParticipantsThe 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.InterventionsThe 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 MeasuresThe primary outcome was 28-day mortality.ResultsAmong 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 RelevanceIn this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo.Trial RegistrationClinicalTrials.gov Identifier: NCT03238742

Xuebijing Injection for Sepsis Treatment: When Will It Be Approved Outside of China?—Reply

“…We do not think that drug equivalence or noninferiority trials are the next step because our study allowed for antibiotics and optimal sepsis management (eg, fluid resuscitation), and there is no well-accepted adjuvant treatment for sepsis. However, we do agree with Dr Hu that a large randomized clinical trial outside of China would be the best pathway to demonstrate the value of Xuebijing injection use in the rest of the world.…”

“…In Reply We appreciate Dr Hu’s interest in and thoughtful criticism of our clinical trial . We agree that it will be challenging to get Xuebijing approved outside of China, but that the obstacles are surmountable…”

“…Our randomized clinical trial was carried out based on numerous early-stage scientific and pharmacological research projects. Xuebijing injection is created by combining traditional Chinese medicine with a number of different chemical compounds.…”

Xuebijing Injection for Sepsis Treatment: When Will It Be Approved Outside of China?

“…To the Editor A recent study by Liu and colleagues reported a reduction in 28-day mortality in patients with sepsis treated with Xuebijing (XBJ), a Chinese medicine compounded injection, compared with placebo. In fact, XBJ has been used in the Chinese market for almost 20 years since its approval in 2004, and it was approved by the National Medical Products Administration of China for the treatment of severe COVID-19 in 2020.…”

“…Lastly, in the study by Dr Liu and colleagues, XBJ was compared with placebo and seemed to be associated with reduced mortality. However, there is still a lack of high-quality drug equivalence and noninferiority trials of XBJ.…”