Clinical trial NCT05391789: Clinical Efficacy of Ulinastatin for Treatment of Sepsis With Systemic Inflammatory Response Syndrome
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Sepsis
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2022-05-26
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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:

1) 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:

1) 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.

The trial will be followed up on days 0, 1, 3, 5, 7 and 28. The changes of sofa on day 7 compared with baseline, all-cause mortality on day 28, ICU hospitalization time, antibiotic use time, SIRS duration, vasoactive drug time, mechanical ventilation time, CRRT time, infection and inflammation indexes, coagulation and fibrinolysis indexes, liver function, renal function, nervous and mental system function and endothelial cell function were compared, To explore the efficacy of ulinastatin in the treatment of adult sepsis patients with systemic inflammatory response syndrome.

Eligibility criteria: Inclusion Criteria:

1. 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
2. diagnosis of sepsis for less than 48 hours
3. 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%)
4. Obtained informed consent signed by the patient or authorized immediate family member

Exclusion Criteria:

1. 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
2. Severe chronic liver disease (Child-Pugh grade C), liver parenchymal lesions with obvious portal hypertension, acute liver failure
3. Chronic renal failure, received dialysis treatment before being selected
4. Severe coagulation function: ISTH-DIC score ≥ 5 points
5. 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
6. Have received Xuebijing, thymosin or gamma globulin treatment within 3 months before being selected for the study
7. Others: allergies to study drugs, pregnancy, breast-feeding, participating in other clinical trials within 3 months, and other conditions deemed unsuitable by the investigator.

Primary outcomes:
measure: delta sofa, ΔSOFA
timeFrame: Day 5
Secondary outcomes:
measure: Sofa vs. baseline change in sofa at randomization (delta sofa, Δ SOFA）
timeFrame: Day 1,3,7
measure: 28 day all-cause mortality
timeFrame: Day 28
measure: ICU hospitalization days
timeFrame: Day 28
measure: antibiotic use days
timeFrame: Day 28
measure: SIRS days
timeFrame: Day 28
measure: vasoactive drugs days
timeFrame: Day 28
measure: mechanical ventilation days
timeFrame: Day 28
measure: CRRT days
timeFrame: Day 28
measure: Blood routine
timeFrame: Day 1,3,5,7
measure: coagulation and fibrinolysis indexes: PT, PLT, D-dimer
timeFrame: Day 1,3,5,7
measure: DIC score
timeFrame: Day 1,3,5,7
measure: AST, ALT, bilirubin
timeFrame: Day 1,3,5,7
measure: urine volume
timeFrame: Day 1,3,5,7
measure: creatinine
timeFrame: Day 1,3,5,7
measure: urea nitrogen
timeFrame: Day 1,3,5,7
measure: blood lactate
timeFrame: Day 1,3,5,7
measure: oxygenation index
timeFrame: Day 1,3,5,7
measure: oxygen saturation
timeFrame: Day 1,3,5,7
measure: Glasgow Coma Scale
timeFrame: Day 1,3,5,7
measure: days of delirium and coma
timeFrame: Day 1,3,5,7
measure: APACHE-II on day 5
timeFrame: Day 5
measure: ADL on day 1,3,5,7;
timeFrame: Day 1,3,5,7
measure: intercellular adhesion factor
timeFrame: Day 1,3,7
measure: concentration of endothelial cell specific molecules
timeFrame: Day 1,3,7
measure: heparan sulfate
timeFrame: Day 1,3,7
measure: lymphocyte subsets and inflammatory factor levels (IL-6, IL-10, CRP, PCT, TNF- α、 HMGB-1）
timeFrame: Day 1,3,7
Other outcomes:
measure: adverse event
timeFrame: Day 28
measure: Serious adverse events
timeFrame: Day 28
measure: Vital signs
timeFrame: Day 28
measure: Blood biochemistry
timeFrame: Day 28
measure: physical examination results
timeFrame: Day 28
measure: electrocardiogram
timeFrame: Day 28
Locations:
city: Jingan
country: China
facility: Huashan Hospital affiliated to Fudan University
state: Shanghai
Study officials:
affiliation: Huashan Hospital
name: Wenhong Wenhong, Professor
role: PRINCIPAL_INVESTIGATOR
References: