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
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 165
- 试验地点
- 1
- 主要终点
- Mean change from baseline in Systemic Immune-Inflammation Index (SII) at Day 5
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
Only participants are blinded to study medication assignment. Investigators, treating physicians and follow-up assessors remain unblinded.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Normal Saline (0.9% NaCl) (Drug)
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.
干预措施: ulinastatin (Drug)
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.
干预措施: ulinastatin (Drug)
结局指标
主要结局
Mean change from baseline in Systemic Immune-Inflammation Index (SII) at Day 5
时间窗: Baseline (before treatment), 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.
次要结局
- 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)
- Mean change from baseline in Sequential Organ Failure Assessment (SOFA) total score at Day 3, Day 5, Day 7(Baseline, Day 3, Day 5, Day 7)
- Cumulative incidence of new-onset organ failure at Day 7(Up to Day 7)
- Correlation coefficients between serial immune-inflammatory marker changes 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(Up to Day 28)
- Incidence of adverse events during treatment(From the start of intervention to 4 weeks after the last study drug administration)
研究者
Xianqiang Chen
Chief Physician
Fujian Medical University Union Hospital