Efficacy and Safety of Ulinastatin in the Treatment of Patients with Sepsis: The ADJUST Trial
In brief
Ulinastatin did not reduce 28-day deaths in patients with sepsis
In this randomized trial, 23.6% of patients given ulinastatin died within 28 days, compared with 22.9% given placebo, with similar results for other mortality and length-of-stay outcomes. Adverse events were more common with ulinastatin, occurring in 56.8% versus 42.7%; the findings do not support routine use for sepsis.
- Journal
- Chest (Q1)
- Published
- 6 November 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Yan Chen, Wei Jiang, Xiangyou Yu, Tongwen Sun, Ruilan Wang, Li Yu, et al.
- PMID
- 42994751
- DOI
- 10.1016/j.chest.2026.10.033
Why clinicians should know about it
- Picked for Critical Care and Intensive Care Medicine (paper of the day, 7 November 2026): Multicentre placebo-controlled sepsis treatment trial
Abstract
BACKGROUND: Urinary trypsin inhibitor (ulinastatin, UTI) has shown potential survival benefits in sepsis; however, conclusive clinical evidence is lacking. RESEARCH QUESTION: In patients with sepsis, does adjunctive ulinastatin, compared with placebo, reduce 28-day all-cause mortality? STUDY DESIGN AND METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, adult ICU patients with sepsis meeting Sepsis-3 criteria within 48 hours of admission were randomized (1:1) to receive intravenous UTI (400,000 IU every 8 hours) or placebo, for up to 10 days in addition to standard care. Randomization was stratified by site and septic shock. The primary endpoint was 28-day all-cause mortality. Secondary endpoints included ICU, hospital, and 90-day mortality, and ICU/hospital length of stay. RESULTS: Of 347 patients randomized, 340 (169 UTI, 171 placebo) received intervention and were included in the safety analysis; after 5 post-intervention withdrawals, 335 (165 UTI, 170 placebo) were included in the intention-to-treat analysis. At 28 days, death had occurred in 39 of 165 patients (23.6%) in the UTI group and in 39 of 170 patients (22.9%) in the placebo group (absolute difference, 0.7% [95% CI -8.4% to 9.7%]; P = .98; hazard ratio 1.03, 95% CI 0.66 to 1.61, P = .90). Secondary outcomes were similar in the two groups. Adverse events occurred in 56.8% (96/169) of UTI and 42.7% (73/171) of placebo patients (absolute difference 14.1%, 95% CI 3.6%-24.6%; P = 0.009). INTERPRETATION: In patients with sepsis, adjunctive UTI did not reduce mortality compared with placebo. Routine use of UTI for sepsis is not supported by these findings. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; https://clinicaltrials.gov; NCT02647554.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.