Herbal infusion seems effective in reducing risk of death from sepsis (EXIT-SEP)

Reference

Liu S, Yao C, Xie J, et al, for the EXIT-SEP Investigators. Effect of an herbal-based injection on 28-day mortality in patients with sepsis. JAMA Intern Med 2023;183(7):647-655.

Synopsis

In this multicenter trial from China, investigators studied the effectiveness of Xuebijing (XBJ) injection in reducing mortality in patients with sepsis. XBJ is an herbal preparation shown to have anti-inflammatory and anticoagulation properties in animal studies, as well as a survival benefit in a randomized study of patients with severe pneumonia. The current study included patients aged 18 to 75 who were admitted to an intensive care unit with a diagnosis of sepsis and a Sequential Organ Failure Assessment (SOFA) score of 2 to 13. Those receiving immunosuppressants or those with unresectable tumors, hematologic disease, or severe liver or kidney dysfunction were excluded, among others. Patients were randomized to receive either 100 mL XBJ intravenously every 12 hours for 5 days (n = 911) or matching placebo (n = 906). All patients received sepsis management, including maintenance of blood pressure, early antibiotic administration, and early treatment of infection source. The 2 groups were balanced at baseline in demographics, comorbidities, and illness severity. Approximately 75% of the patients had lung or abdominal infections. The mean SOFA score in both groups was 7.1. Analysis was by intention to treat. Loss to follow-up was slightly greater in the XBJ group than in the placebo group (3.6% vs 2.6%). For the primary outcome of all-cause mortality at 28 days, the XBJ group fared better than the placebo group (18.8% vs 26.1%; P < .001). On average, treating 14 patients with XBJ may prevent one additional death at 28 days. This number needed to treat (NNT) is consistent with the NNT for 28-day mortality in the XBJ and severe pneumonia randomized study mentioned previously. A similar percentage of patients in the 2 groups experienced adverse events (22.9% in XBJ group and 25.3% in placebo group). The most common adverse events in the XBJ group were liver enzyme elevation and leukocytosis. Of note, a homogeneous study population and a greater loss to follow-up in the experimental group may have confounded the results of this study. Additionally, although XBJ has been approved for use in China since 2004, it would have a difficult path to approval in the United States, according to an accompanying editorial, given its herbal preparation and evidence of effectiveness from only a single study.