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The Innovation Medicine > 2025 Vol. 3 > No. 4 > 100164
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Association of Xuebijing use with 28-day mortality in sepsis: An external validation study using real-world ICU data

  • 1.

    Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100010, China

  • 2.

    Good Clinical Practice Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100010, China

  • 3.

    Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China

  • 4.

    Health Care Policy and Aging Research, Rutgers The State University of New Jersey, New Brunswick NJ08901, USA

  • 5.

    Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing 100010, China

  • 6.

    Key Laboratory of Chinese Internal Medicine of the Ministry of Education and Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100010, China

  • 7.

    These authors contributed equally

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  • Corresponding authors: liuyantcm@bucm.edu.cn (Y.L.); saga618@126.com (C.Z.)
  • Received Date:  July 30, 2025
    Accepted Date:  October 23, 2025
    Published Online:  October 31, 2025
The Innovation Medicine  3(4),  https://doi.org/10.59717/j.xinn-med.2025.100164  |  Cite this article
    GRAPHICAL ABSTRACT
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    1. Sepsis is a life-threatening condition with few proven drug treatments worldwide.

      Xuebijing injection (XBJ), a Chinese herbal medicine, showed benefits for sepsis patients in Chinese trials.

      We performed an external validation using U.S. ICU data (Medical Information Mart for Intensive Care IV, MIMIC-IV).

      Compared to the MIMIC-IV cohort, trial emulation showed XBJ lowered 28-day death risk (HR 0.48).

    • ABSTRACT
  • BackgroundMost pharmacologic interventions for sepsis have failed to show survival benefits in randomized trials. Xuebijing injection (XBJ), an approved intravenous drug widely used in China for sepsis, reduced mortality in two large randomized trials. However, its generalizability to non-Chinese populations remains uncertain. Our study aimed to assess the potential generalizability of the survival benefit of XBJ, previously observed in a Chinese randomized trial, to a non-Chinese ICU population and evaluated whether the treatment effect size was consistent across these different clinical settings.
    MethodsWe conducted a retrospective comparative effectiveness study, conceptualized as a single-arm trial of XBJ with an external control cohort from the MIMIC-IV database, designed using trial emulation principles aligned with the EXIT-SEP trial. Patients with Sepsis-3 septic shock were included. The primary outcome was time to 28-day all-cause mortality. Propensity scores were estimated with generalized boosted models, overlap weighting was applied, and missing data were handled with multiple imputation. Secondary outcomes included ICU-free days, ventilator-free days, and hospital length of stay.
    ResultsAmong 911 patients treated with XBJ and 8,764 controls, unadjusted 28-day mortality rates were 18.1% and 15.5%, respectively. In the primary overlap-weighted analysis, XBJ was associated with a significantly reduced risk of 28-day mortality compared with external controls (HR, 0.48; 95% CI, 0.31–0.73). Findings were consistent across sensitivity analyses. ICU and hospital stays were longer among XBJ-treated patients (ICU: 10.3 vs 6.7; difference, 3.7 days [95% CI, 2.6–4.7]; hospital: 16.2 vs 12.4; difference, 4.0 days [95% CI, 2.6–5.4]).
    ConclusionsIn this external validation using real-world ICU data, XBJ use was associated with reduced 28-day mortality among patients with sepsis. These findings support its potential generalizability beyond the original trial population but warrant confirmation in prospective studies across diverse settings.
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  • Cite this article:

    Li Y., Kang J., Liu S., et al. (2025). Association of Xuebijing use with 28-day mortality in sepsis: An external validation study using real-world ICU data. The Innovation Medicine 3:100164. https://doi.org/10.59717/j.xinn-med.2025.100164
    Li Y., Kang J., Liu S., et al. (2025). Association of Xuebijing use with 28-day mortality in sepsis: An external validation study using real-world ICU data. The Innovation Medicine 3:100164. https://doi.org/10.59717/j.xinn-med.2025.100164

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