Efficacy and Safety of Shenfu Injection in Patients with Septic Shock: A Randomized Controlled Open-Label Trial with...

To evaluate the clinical efficacy of Shenfu Injection (SFI) in treating patients with septic shock through a randomized controlled trial, and explore the underling mechanisms by network pharmacology.

A prospective, single-center, randomized, open-label, parallel-controlled clinical trial was conducted between November 3, 2022 and May 4, 2025 to assess the effectiveness safety of SFI in 122 patients with septic shock (arterial blood lactate 4.5-7.0 mmol/L). Participants were randomly assigned (1:1) to the experimental or control group using stratified block randomization. In addition to the standard care recommended by guidelines, the treatment group received SFI (100 mL) combined with 0.9% saline (100 mL), while the control group received 0.9% saline (200 mL), both via intravenous infusion over 60 min once daily for 7 consecutive days and followed by a 28-d follow-up period. Primary outcomes included 28-d all-cause mortality. Secondary outcomes comprised duration of hospital and intensive care unit (ICU) stays, duration of mechanical ventilation, arterial blood lactate levels, norepinephrine dose, mean arterial pressure (MAP), lactate clearance, left ventricular ejection fraction (LVEF), creatine kinase-MB (CK-MB), and troponin I (TnI) levels on day 7. Aderverse events were recorded and compared between groups. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to elucidate the underlying mechanisms.

The 28-d all-cause mortality was 41.0% (25/61) in the SFI group compared with 50.8% (31/61) in the control group (P=0.271). The 7-d all-cause mortality was significantly lower in the SFI group (4.9%, 3/61) compared with the control group (16.4%, 10/61; P=0.046). On day 7 post-enrollment, the norepinephrine dose in the SFI group was significantly lower than that in the control group [1.48 (1.12, 1.82) vs. 2.37 (1.68, 2.80) µ,g·kg^-1·min^-1, P<0.01]. Similarly, lactate levels in the SFI group were significantly lower than those in the control group [3.02 (2.50, 3.33) vs. 4.37 (3.78, 4.90) mmol/L] on day 7 (P<0.01). In addition, the SFI group demonstrated significantly higher lactate clearance, MAP, and LVEF, alongside significantly lower CK-MB and TnI levels compared with the control group on day 7 (all P<0.01). No significant differences in adverse events were observed between two groups (5/59 vs. 3/61, P>0.05). Network pharmacology analysis identified 102 intersection target genes between SFI- and septic shock-related targets, which were significantly enriched in several sepsis-related pathways, such as the IL-17, TNF, and PI3K-Akt signaling pathways.

In patients with septic shock and lactate levels of 4.5-7.0 mmol/L, adjunctive SFI did not significantly reduce 28-d all-cause mortality. However, it was associated with a significant reduction in 7-d mortality and improved hemodynamic, metabolic, and cardiac parameters by day 7, with a favorable safety profile. Network pharmacology analysis suggests its potential mechanisms may involve modulation of inflammatory and cellular signaling pathways. (Trial registration No. ChiCTR2200065122).