Clinical Efficacy of Ulinastatin for Treatment of Sepsis With Systemic Inflammatory Response Syndrome: a Multicenter, Randomized, Double-blind, Multi Dose and Placebo-controlled Clinical Trial.
试验速览
- 阶段
- 3 期
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- delta sofa, ΔSOFA
研究概览
简要总结
Sepsis is a life-threatening organ dysfunction caused by the maladjusted response of the host to infection. It is a clinical syndrome with high mortality. Studies have confirmed that many cytokines play a vital role in the pathogenesis of sepsis. Ulinastatin (UTI) is a glycoprotein that exists in human blood and can be isolated and purified from human urine. It is a broad-spectrum protease inhibitor. Previous studies have shown that Ulinastatin may have the effect of treating sepsis.
120 septic patients with systemic inflammatory response syndrome would be recruited and randomly assigned to the ordinary dose group, high dose group and placebo control group according to the ratio of 1:1:1.
The trial will be followed up on days 0, 1, 3, 5, 7 and 28. Sofa on day 7 compared with baseline and all-cause mortality on day 28 were investigated to explore the efficacy of ulinastatin in the treatment of adult sepsis patients with systemic inflammatory response syndrome.
详细描述
The study plans to recruit 120 septic patients with systemic inflammatory response syndrome. After signing the informed consent, they will be included as day 0. They will be randomly assigned to the ordinary dose group, high dose group and placebo control group according to the ratio of 1:1:1, and the evaluation of basic clinical information of subjects will be supplemented and improved.The ordinary dose group will receive 400000 units of ulinastatin, which will be injected intravenously every 8 hours, The high-dose group will receive 800000 units of ulinastatin intravenously every 8 hours, and the control group will use equal volume solvent (50ml normal saline) as placebo intravenously every 8 hours. When the patient does not have systemic inflammatory response syndrome, the dose will be halved and then continue to be used for 2 days. The total course of Ulinastatin injection shall be at least 3 days.
Inclusion criteria:
- Adults ≥ 18 years old and ≤ 80 years old 2) meet the sepsis-3.0 standard specified by the American Society of critical care medicine and the European Society of critical care medicine 3) sepsis diagnosis time < 48h 4) systemic inflammatory response syndrome (SIRS) 5) obtain the informed consent signed by the patient or authorized immediate family members
Exclusion criteria:
- Congestive heart failure, NYHA grade IV cardiac function, cerebrovascular accident or acute coronary syndrome within 3 months, cardiac arrest in this hospital or within 7 days, non infectious cardiogenic shock, uncontrolled acute bleeding 2) severe chronic liver disease (child Pugh grade C), liver parenchymal disease with significant portal hypertension Acute liver failure 3) chronic renal failure, who had received dialysis treatment before enrollment 4) severe abnormal coagulation function: isth-dic score ≥ 5 points 5) significant immune abnormalities / damage: organ or bone marrow transplantation and moderate and severe leucopenia within 3 months before screening, such as neutrophils < 1.5 × 109 / L, received radiotherapy or chemotherapy within 3 months, HIV seropositive, hematological / lymphatic system tumor active period 6) received Xuebijing, thymosin or gamma globulin treatment within 3 months before study enrollment 7) others: allergic to study drugs, pregnancy, lactation, participated in other clinical trials within 3 months, and other situations that researchers think are not suitable to participate.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •sepsis-3 specified by SCCM and ESICM 1) suspected or confirmed infection: diagnosed by a clinician 2) evidence of acute organ dysfunction: for patients without chronic organ dysfunction in the past (assuming a baseline SOFA score of 0): sofa ≥ 2 points from 48 hours before diagnosis of infection to 24 hours after diagnosis of infection for patients with chronic organ dysfunction in the past (SOFA score should be based on baseline): the increase of sofa ≥ 2 points from 48 hours before diagnosis of infection to 24 hours after diagnosis of infection
- •diagnosis of sepsis for less than 48 hours
- •Systemic inflammatory response syndrome (SIRS) 1) body temperature > 38 ℃ or < 36 ℃ 2) heart rate > 90 3) respiratory rate> 20 4) WBC count > 12 × 10 ^ 9 / L or < 4 × 10^9/L (>12000/ μ L or < 4000/ μ L or immature granulocytes > 10%)
- •Obtained informed consent signed by the patient or authorized immediate family member
排除标准
- •Congestive heart failure (NYHA heart function level 4), cerebrovascular accident or acute coronary syndrome within 3 months, cardiac arrest within 7 days of this hospitalization, non-infectious cardiogenic shock, uncontrolled acute bleeding
- •Severe chronic liver disease (Child-Pugh grade C), liver parenchymal lesions with obvious portal hypertension, acute liver failure
- •Chronic renal failure, received dialysis treatment before being selected
- •Severe coagulation function: ISTH-DIC score ≥ 5 points
- •Significant immune abnormality/injury: received organ or bone marrow transplantation within 3 months before screening, moderate to severe leukopenia such as neutrophils <1.5×10^9/L, received radiotherapy or chemotherapy within 3 months , HIV seropositivity, active blood/lymphatic system tumor
- •Have received Xuebijing, thymosin or gamma globulin treatment within 3 months before being selected for the study
- •Others: allergies to study drugs, pregnancy, breast-feeding, participating in other clinical trials within 3 months, and other conditions deemed unsuitable by the investigator.
研究组 & 干预措施
normal dose
Patients would be given 400000 units of ulinastatin (specification: 100000 units / vial) dissolved in 50 ml of 0.9% normal saline intravenously for at least 1 hour, once every 8 hours. It is evaluated by the attending doctor every day. When the patient does not have systemic inflammatory response syndrome (SIRS), halve the dose and continue to use it for 2 days, with a total course of treatment of at least 3 days
干预措施: Ulinastatin (Drug)
high dose
Patients would be given 800000 units of ulinastatin (specification: 100000 units / vial) dissolved in 50 ml of 0.9% normal saline intravenously for at least 1 hour, once every 8 hours. It is evaluated by the attending doctor every day. When the patient does not have systemic inflammatory response syndrome (SIRS), halve the dose and continue to use it for 2 days, with a total course of treatment of at least 3 days
干预措施: Ulinastatin (Drug)
placebo
Patients would be given 50 ml of 0.9% normal saline intravenously for at least 1 hour once every 8 hours.It is evaluated by the attending doctor every day. When the patient does not have systemic inflammatory response syndrome (SIRS), continue to use it for 2 days, with a total course of treatment of at least 3 days.
干预措施: Placebo (Drug)
结局指标
主要结局
delta sofa, ΔSOFA
时间窗: Day 5
Sequential organ failure asses(SOFA) of day 5 , compared with the baseline.
次要结局
- vasoactive drugs days(Day 28)
- intercellular adhesion factor(Day 1,3,7)
- concentration of endothelial cell specific molecules(Day 1,3,7)
- heparan sulfate(Day 1,3,7)
- mechanical ventilation days(Day 28)
- CRRT days(Day 28)
- ICU hospitalization days(Day 28)
- antibiotic use days(Day 28)
- SIRS days(Day 28)
- 28 day all-cause mortality(Day 28)
- Sofa vs. baseline change in sofa at randomization (delta sofa, Δ SOFA）(Day 1,3,7)
- coagulation and fibrinolysis indexes: PT, PLT, D-dimer(Day 1,3,5,7)
- DIC score(Day 1,3,5,7)
- urine volume(Day 1,3,5,7)
- urea nitrogen(Day 1,3,5,7)
- blood lactate(Day 1,3,5,7)
- oxygenation index(Day 1,3,5,7)
- oxygen saturation(Day 1,3,5,7)
- Glasgow Coma Scale(Day 1,3,5,7)
- days of delirium and coma(Day 1,3,5,7)
- APACHE-II on day 5(Day 5)
- ADL on day 1,3,5,7;(Day 1,3,5,7)
- Blood routine(Day 1,3,5,7)
- creatinine(Day 1,3,5,7)
- AST, ALT, bilirubin(Day 1,3,5,7)
- lymphocyte subsets and inflammatory factor levels (IL-6, IL-10, CRP, PCT, TNF- α、 HMGB-1）(Day 1,3,7)
研究者
Wen-hong Zhang
chief physician, professor
Huashan Hospital