Herbal-based injection may reduce mortality in sepsis patients: EXIT-SEP trial

In the study involving 1817 patients with sepsis, the 28-day mortality rate in patients who received the herbal-based Xuebijing injection (XBJ) was 18.8% versus 26.1% in the placebo group, a significant difference. Compared with a placebo, XBJ could also reduce ICU mortality and was linked with cumulative mechanical ventilation–free and ICU-free days in sepsis patients during the 28-day follow-up period.

Sepsis is a systemic disease that worsens rapidly with multiple organ dysfunction. A dysregulated inflammatory response to infection causes it and remains the leading cause of death worldwide. Several investigational therapies have targeted the various biological pathways of sepsis but have failed in large, randomized clinical trials, and none have shown a significant mortality benefit.

Xuebijing injection is a herbal-based intravenous preparation licensed in 2004 by the National Medical Products Administration (NMPA, China) for treating multiple organ dysfunction syndrome and sepsis. It is suggested that Xuebijing injection possesses an array of activities associated with its protection mechanism in sepsis.

To further investigate the protective role of Xuebijing injection in sepsis, Songqiao Liu, Southeast University, Nanjing, Jiangsu, China, and colleagues aimed to determine the effect of XBJ versus placebo on 28-day mortality among sepsis patients in a multicenter, randomized double-blind, placebo-controlled trial (EXIT-SEP).

The trial was conducted in ICUs (intensive care units) at 45 sites, comprising 1817 sepsis patients present for below 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled.

Nine hundred eleven patients received an intravenous infusion of XBJ (100 mL), and 906 received volume-matched saline placebo every 12 hours for five days. The study's primary outcome was 28-day mortality.

The authors reported the following findings:

• Among the 1817 randomized patients (mean age, 56.5 years; 66.0% men), 96.9% completed the trial.
• In these patients, the 28-day mortality rate significantly differed between the placebo and XBJ groups (26.1% versus 18.8% patients, respectively). The absolute risk difference was 7.3 percentage points.
• The incidence of adverse events was 25.3% in the placebo group and 22.9% in the XBJ group.

"In this randomized clinical trial of sepsis patients, an IV infusion of XBJ at a dose of 100 mL every 12 hours for five days remarkably reduced 28-day mortality and had a safety profile acceptable within this clinical trial's context," the researchers concluded.

Reference:

Liu S, Yao C, Xie J, et al. Effect of an Herbal-Based Injection on 28-Day Mortality in Patients With Sepsis: The EXIT-SEP Randomized Clinical Trial. JAMA Intern Med. Published online May 01, 2023. doi:10.1001/jamainternmed.2023.0780