Ulinastatin on Systemic Immune-Inflammation in Patients With Complicated Intra-Abdominal Infection

NCT07672496 | Not Yet Recruiting

• 1 other identifier: FJXH-2026-0506
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Complicated Intra-abdominal Infection (cIAI); Systemic Inflammatory Response; Sepsis; Immune Dysfunction

Keywords

immune dysfunction; Complicated intra-abdominal infection; Ulinastatin; SII; inflammation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Mean change from baseline in Systemic Immune-Inflammation Index (SII) at 48 Hours

  Baseline, 48 hours

• Mean change from baseline in C-reactive protein (CRP) at Day 1, Day 3, Day 5

  Baseline, Day 1, Day 3, Day 5

• Mean change from baseline in Interleukin-6 (IL-6) at Day 1, Day 3, Day 5

  Baseline, Day 1, Day 3, Day 5

• Mean change from baseline in CD4+ T cell count at Day 1, Day 3, Day 5

  Baseline, Day 1, Day 3, Day 5

• Mean change from baseline in CD4+/CD8+ T cell ratio at Day 1, Day 3, Day 5

  Baseline, Day 1, Day 3, Day 5

Study Arms (3)

Low-dose Ulinastatin

EXPERIMENTAL

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

High-dose Ulinastatin

EXPERIMENTAL

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

Normal Saline Placebo

PLACEBO COMPARATOR

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)

Interventions

ulinastatin DRUG

Low dose:100000 IU iv tid×5d; High dose:300000 IU iv tid×5d, diluted in 100mL normal saline

High-dose Ulinastatin; Low-dose Ulinastatin

Normal Saline (0.9% NaCl) DRUG

Equal-volume 0.9% normal saline iv tid×5d as placebo

Normal Saline Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written informed consent voluntarily.
• Age ≥ 18 years old, any gender.
• 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.
• Baseline Sequential Organ Failure Assessment (SOFA) score ≥ 2 points.

You may not qualify if:

• 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.
• 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.
• Patients with active malignant tumors, pregnancy, or severe psychiatric disorders.
• American Society of Anesthesiologists (ASA) physical status grade IV or above.
• Severe coagulation disorder defined as ISTH-DIC score ≥ 5 points.
• Critically ill patients with expected death within 48 hours after admission.
• Known allergy to ulinastatin or any ingredients of the study preparation.
• Any condition that, in the judgment of the principal investigator, makes the patient inappropriate for trial participation.

Sponsors & Collaborators

• Fujian Medical University Union Hospital: lead

Study Sites (1)

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

Location

Related Publications (8)

• 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.

  PMID: 35634310 BACKGROUND

• 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.

  PMID: 24737258 BACKGROUND

• 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.

  PMID: 12964125 BACKGROUND

• 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.

  PMID: 29334554 BACKGROUND

• 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.

  PMID: 40735314 BACKGROUND

• 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.

  PMID: 36209190 BACKGROUND

• 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.

  PMID: 36763198 BACKGROUND

• 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.

  PMID: 38990709 BACKGROUND

MeSH Terms

Conditions

Sepsis; Immune System Diseases; Inflammation

Interventions

urinastatin; Saline Solution

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Only participants are blinded to study medication assignment. Investigators, treating physicians and follow-up assessors remain unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Model Details: Three-arm parallel assignment design. Subjects are randomly divided into low-dose ulinastatin group, high-dose ulinastatin group and normal saline control group at a 1:1:1 ratio, all receiving standardized basic treatment simultaneously.

Study Record Dates

• First Submitted: June 3, 2026
• First Posted: June 29, 2026
• Study Start (Estimated): October 30, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: June 29, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)