Ulinastatin on Systemic Immune-Inflammation in Patients With Complicated Intra-Abdominal Infection (UTI-cIAI)

A Single-Center Randomized Controlled Pilot Study on the Effect of Ulinastatin on Systemic Immune and Inflammatory Response in Patients With Complicated Intra-Abdominal Infection

Complicated intra-abdominal infection (cIAI) triggers dysregulated systemic inflammation and immune paralysis leading to high organ failure and death risk. Ulinastatin is a protease inhibitor with anti-inflammatory properties, but its dose-related effects on immune-inflammation of cIAI patients remain unclear. This single-center single-blinded three-arm randomized controlled pilot study enrolls adult cIAI patients (≥18 years, SOFA≥2) at Fujian Medical University Union Hospital. Eligible patients are randomized into low-dose ulinastatin, high-dose ulinastatin and normal saline placebo groups (1:1:1, 5 days intravenous treatment plus standard care), total planned enrollment 165 participants after 10% dropout adjustment. Primary endpoint is Day5 change of Systemic Immune-Inflammation Index (SII); secondary outcomes include serial inflammatory biomarkers, SOFA variation, organ dysfunction, hospitalization duration, 28-day mortality and safety profiles. This pilot aims to clarify ulinastatin's immune-modulating effect and inform future large RCT design.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis; Complicated Intra-abdominal Infection (cIAI); Systemic Inflammatory Response; Immune Dysfunction
• Intervention / Treatment: Drug: ulinastatin; Drug: Normal Saline (0.9% NaCl)

Detailed Description

This is a single-center, randomized, single-blind, three-arm parallel-group superiority pilot clinical trial performed at Fujian Medical University Union Hospital. Randomization sequence is generated with SAS 9.3 software, and random grouping is implemented by sealed envelope method at a 1:1:1 allocation ratio (low-dose ulinastatin : high-dose ulinastatin : normal saline control =1:1:1). A total of 165 participants are planned, with 55 subjects in each group after accounting for an anticipated 10% dropout rate.

All enrolled patients are adults aged ≥18 years diagnosed with complicated intra-abdominal infection (cIAI) within 48 hours, confirmed by clinical manifestation, laboratory tests and abdominal imaging, accompanied by SOFA score ≥2. Subjects with severe immunodeficiency, end-stage liver or renal disease, malignancy, pregnancy, hypersensitivity to ulinastatin and other severe comorbidities are excluded. Written informed consent is obtained prior to any study-related procedures.

All participants receive standardized routine management including surgical source control, antibacterial therapy and organ function supportive treatment. Intervention regimens last for consecutive 5 days via intravenous drip: low-dose group receives ulinastatin 100,000 IU three times daily diluted in 100 mL normal saline; high-dose group receives ulinastatin 300,000 IU three times daily diluted in 100 mL normal saline; control group receives equal volume of sterile normal saline three times daily as placebo. For patients with progressive organ dysfunction after 24-48 hours without improvement, rescue high-dose ulinastatin is allowed per investigator's clinical judgment.

Primary endpoint is the absolute change of Systemic Immune-Inflammation Index (SII) from baseline to treatment Day 5. Secondary endpoints include dynamic changes of CRP, PCT, IL-6, NLR, PLR, LMR, CLR, CD4⁺/CD8⁺ T cell counts at Days 1,3,5 and 7; sequential SOFA score changes; cumulative incidence of new organ failure within 7 and 14 days; ICU and total hospital stay duration; reoperation rate, secondary infection rate, in-hospital and 28-day all-cause mortality. Subgroup analyses are preset stratified by operation type, pathogenic bacteria (multidrug-resistant pathogen or candidiasis) and baseline disease severity (MPI/SOFA score).

All adverse events (AEs) from informed consent to 4 weeks after final study medication are documented following CTCAE Version 5.0. All serious adverse events (SAEs) must be reported to the sponsor (Techpool Bio-Pharma Co., Ltd.) within 24 hours. Study will be prematurely terminated if excessive unexpected severe adverse events occur or interim analysis demonstrates no meaningful intergroup difference in primary inflammatory markers. Study monitoring, source document verification and data management are conducted in accordance with GCP and Declaration of Helsinki principles.

• Study Type: Interventional
• Enrollment (Estimated): 165
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
      • Contact: JunRong Zhang, MD; Phone Number: 0591-83357896; Email: foxbaby34@163.com
      • Principal Investigator: QinYong Weng, MD
      • Sub-Investigator: XianQiang Chen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able to provide written informed consent voluntarily.
2. Age ≥ 18 years old, any gender.
3. Diagnosed with severe complicated intra-abdominal infection (cIAI) within 48 hours, consistent with the 2025 expert consensus for cIAI diagnosis. Diagnosis is confirmed by clinical symptoms (fever, abdominal pain, distension, etc.), abdominal imaging (CT/ultrasound/MRI), intraoperative findings, or positive pathogen culture of abdominal drainage fluid.
4. Baseline Sequential Organ Failure Assessment (SOFA) score ≥ 2 points.

Exclusion Criteria:

1. Severe immune deficiency conditions, including AIDS, prior solid organ or bone marrow transplantation, HIV infection with CD4 count < 200 cells/mm³, long-term high-dose glucocorticoid therapy (prednisone > 20 mg/day), ongoing chemotherapy for malignant tumors, or absolute neutrophil count < 1000 cells/mm³.
2. Severe irreversible underlying diseases, including chronic renal failure requiring dialysis, Child-Pugh grade C liver disease, liver disease with severe portal hypertension, or acute liver failure.
3. Patients with active malignant tumors, pregnancy, or severe psychiatric disorders.
4. American Society of Anesthesiologists (ASA) physical status grade IV or above.
5. Severe coagulation disorder defined as ISTH-DIC score ≥ 5 points.
6. Critically ill patients with expected death within 48 hours after admission.
7. Known allergy to ulinastatin or any ingredients of the study preparation.
8. Any condition that, in the judgment of the principal investigator, makes the patient inappropriate for trial participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-dose Ulinastatin; Intravenous infusion of ulinastatin 100,000 IU, three times daily for 5 consecutive days, diluted in 100 mL normal saline, administered on the basis of standardized routine treatment for complicated intra-abdominal infection.	Drug: ulinastatin; Low dose:100000 IU iv tid×5d; High dose:300000 IU iv tid×5d, diluted in 100mL normal saline
Experimental: High-dose Ulinastatin; Intravenous infusion of ulinastatin 300,000 IU, three times daily for 5 consecutive days, diluted in 100 mL normal saline, administered on the basis of identical standardized routine treatment.	Drug: ulinastatin; Low dose:100000 IU iv tid×5d; High dose:300000 IU iv tid×5d, diluted in 100mL normal saline
Placebo Comparator: Normal Saline Placebo; Identical standard routine treatment. Equal volume of 0.9% normal saline infused intravenously three times daily for 5 days as placebo. Rescue high-dose ulinastatin can be given per investigator's judgment for treatment failure patients.	Drug: Normal Saline (0.9% NaCl); Equal-volume 0.9% normal saline iv tid×5d as placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in Systemic Immune-Inflammation Index (SII) at Day 5	The Systemic Immune-Inflammation Index (SII) is calculated from routine blood test results as platelet count multiplied by neutrophil count divided by lymphocyte count. The mean change in SII values from baseline to Day 5 will be compared across the three groups to assess the immunomodulatory effect of ulinastatin on systemic immune-inflammatory status in patients with complicated intra-abdominal infection.	Baseline (before treatment), Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in Systemic Immune-Inflammation Index (SII) at 48 Hours	The Systemic Immune-Inflammation Index (SII) is calculated from routine blood test results as platelet count multiplied by neutrophil count divided by lymphocyte count. We will calculate the mean change in SII at 48 hours relative to baseline, and compare these changes among the three treatment groups to evaluate the sustained anti-inflammatory and immunomodulatory effects of ulinastatin.	Baseline, 48 hours
Mean change from baseline in C-reactive protein (CRP) at Day 1, Day 3, Day 5	Serum CRP levels will be measured at scheduled time points. Changes from baseline will be compared among groups to evaluate inflammatory status.	Baseline, Day 1, Day 3, Day 5
Mean change from baseline in Interleukin-6 (IL-6) at Day 1, Day 3, Day 5	Serum IL-6 levels will be measured at scheduled time points. Changes from baseline will be compared among groups to evaluate inflammatory status.	Baseline, Day 1, Day 3, Day 5
Mean change from baseline in CD4+ T cell count at Day 1, Day 3, Day 5	Peripheral CD4+ T cell count will be measured at scheduled time points. Changes from baseline will be compared among groups.	Baseline, Day 1, Day 3, Day 5
Mean change from baseline in CD4+/CD8+ T cell ratio at Day 1, Day 3, Day 5	CD4+/CD8+ ratio will be calculated at scheduled time points. Changes from baseline will be compared among groups.	Baseline, Day 1, Day 3, Day 5
Mean change from baseline in Sequential Organ Failure Assessment (SOFA) total score at Day 3, Day 5, Day 7	The full name of the scale is Sequential Organ Failure Assessment (SOFA) score. The score ranges from a minimum of 0 to a maximum of 24. Higher SOFA scores indicate worse organ dysfunction and poorer clinical outcomes. SOFA scores will be assessed at baseline and follow-up time points. Score changes will be compared to evaluate organ function improvement.	Baseline, Day 3, Day 5, Day 7
Cumulative incidence of new-onset organ failure at Day 7	New-onset organ failure is defined as an increase in the Sequential Organ Failure Assessment (SOFA) score of ≥2 points from baseline. The cumulative incidence of new organ failure occurring within 7 days after treatment initiation will be calculated and compared across the three study groups.	Up to Day 7
Correlation coefficients between serial immune-inflammatory marker changes and 28-day all-cause mortality	Serial dynamic values of systemic immune-inflammatory markers, including Systemic Immune-Inflammation Index (SII), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Lymphocyte-to-Monocyte Ratio (LMR), and CRP-to-Lymphocyte Ratio (CLR), will be collected from baseline to Day 5. Pearson correlation analysis will be performed to evaluate the correlation coefficients between dynamic changes of these markers and 28-day all-cause mortality.	Baseline, Day 1, Day 3, Day 5, up to Day 28
Proportion of participants with 28-day all-cause mortality	Vital status followed up to Day 28 after randomization. The percentage of participants who die from any cause within 28 days will be reported and compared between groups.	Up to Day 28
Incidence of adverse events during treatment	All adverse events and serious adverse events occurring during the treatment and follow-up period will be recorded in detail. The incidence, severity and correlation with study drugs will be analyzed to evaluate the safety profile of ulinastatin.	From the start of intervention to 4 weeks after the last study drug administration

Collaborators and Investigators

• Sponsor: Fujian Medical University Union Hospital

Publications and helpful links

General Publications

• Karnad DR, Bhadade R, Verma PK, Moulick ND, Daga MK, Chafekar ND, Iyer S. Intravenous administration of ulinastatin (human urinary trypsin inhibitor) in severe sepsis: a multicenter randomized controlled study. Intensive Care Med. 2014 Jun;40(6):830-8. doi: 10.1007/s00134-014-3278-8. Epub 2014 Apr 16.
• Aziz MH, Sideras K, Aziz NA, Mauff K, Haen R, Roos D, Saida L, Suker M, van der Harst E, Mieog JS, Bonsing BA, Klaver Y, Koerkamp BG, van Eijck CH. The Systemic-immune-inflammation Index Independently Predicts Survival and Recurrence in Resectable Pancreatic Cancer and its Prognostic Value Depends on Bilirubin Levels: A Retrospective Multicenter Cohort Study. Ann Surg. 2019 Jul;270(1):139-146. doi: 10.1097/SLA.0000000000002660.
• Liu D, Huang SY, Sun JH, Zhang HC, Cai QL, Gao C, Li L, Cao J, Xu F, Zhou Y, Guan CX, Jin SW, Deng J, Fang XM, Jiang JX, Zeng L. Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options. Mil Med Res. 2022 Oct 9;9(1):56. doi: 10.1186/s40779-022-00422-y.
• Chen L, Jin S, Yang M, Gui C, Yuan Y, Dong G, Zeng W, Zeng J, Hu G, Qiao L, Wang J, Xi Y, Sun J, Wang N, Wang M, Xing L, Yang Y, Teng Y, Hou J, Bi Q, Cai H, Zhang G, Hong Y, Zhang Z. Integrated Single Cell and Bulk RNA-Seq Analysis Revealed Immunomodulatory Effects of Ulinastatin in Sepsis: A Multicenter Cohort Study. Front Immunol. 2022 May 11;13:882774. doi: 10.3389/fimmu.2022.882774. eCollection 2022.
• Lim YP, Bendelja K, Opal SM, Siryaporn E, Hixson DC, Palardy JE. Correlation between mortality and the levels of inter-alpha inhibitors in the plasma of patients with severe sepsis. J Infect Dis. 2003 Sep 15;188(6):919-26. doi: 10.1086/377642. Epub 2003 Aug 26.
• Feier CVI, Motoc A, Muntean C, Vonica RC, Gaborean V, Olariu S, Murariu MS. Systemic inflammatory indices and age-dependent severity in acute appendicitis: a retrospective cohort study. Front Immunol. 2025 Jul 15;16:1620459. doi: 10.3389/fimmu.2025.1620459. eCollection 2025.
• Nebelung H, Wotschel N, Held HC, Kirchberg J, Weitz J, Radosa CG, Laniado M, Hoffmann RT, Plodeck V. ICU patients with infectious complications after abdominopelvic surgery: Is thoracic CT in addition to abdominal CT helpful? Ann Intensive Care. 2023 Feb 10;13(1):6. doi: 10.1186/s13613-023-01104-1.
• Huston JM, Barie PS, Dellinger EP, Forrester JD, Duane TM, Tessier JM, Sawyer RG, Cainzos MA, Rasa K, Chipman JG, Kao LS, Pieracci FM, Colling KP, Heffernan DS, Lester J; Therapeutics and Guidelines Committee. The Surgical Infection Society Guidelines on the Management of Intra-Abdominal Infection: 2024 Update. Surg Infect (Larchmt). 2024 Aug;25(6):419-435. doi: 10.1089/sur.2024.137. Epub 2024 Jul 11.

Study record dates

Study Major Dates

• Study Start (Estimated): October 30, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: June 3, 2026
• First Submitted That Met QC Criteria: June 26, 2026
• First Posted (Actual): June 29, 2026

Study Record Updates

• Last Update Posted (Actual): June 29, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: inflammation; Complicated intra-abdominal infection; Ulinastatin; immune dysfunction; SII
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Pathological Conditions, Signs and Symptoms; Inflammation; Sepsis; Immune System Diseases; Pharmaceutical Preparations; Crystalloid Solutions; Isotonic Solutions; Solutions; Saline Solution; urinastatin
• Other Study ID Numbers: FJXH-2026-0506

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be made publicly available for this clinical trial. Relevant study protocol, aggregate clinical outcome results, and summary analysis data may be published in peer-reviewed journals or presented at academic conferences after the completion of the trial. Data access is restricted to the study research team only due to institutional and participant privacy requirements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No