Clinical Efficacy of Ulinastatin for Treatment of Sepsis With Systemic Inflammatory Response Syndrome

Overview

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 were recruited and randomly assigned to the ordinary-dose group, high-dose group, or placebo in a 1:1:1 ratio. The trial was followed up on days 0, 1, 3, 5, 7 and 28. The primary outcome is the change in Sequential Organ Failure Assessment (SOFA) score from baseline to Day 5 (ΔSOFA). All-cause mortality at day 28 is a secondary outcome.

This completed multicenter randomized trial enrolled 120 adults with sepsis and systemic inflammatory response syndrome (SIRS). After informed consent, the enrollment day was Day 0. Participants were randomly assigned 1:1:1 to an ordinary-dose group, a high-dose group, or a placebo control group, and baseline clinical information was collected. The ordinary-dose group received ulinastatin 400,000 units intravenously every 8 hours. The high-dose group received ulinastatin 800,000 units intravenously every 8 hours. The control group received an equal volume of 0.9% saline (50 mL) intravenously every 8 hours. When SIRS criteria were no longer met, the assigned dose (or matching placebo volume) was halved and continued; treatment lasted at least 3 days and up to 7 days. Inclusion criteria: 1\) Adults ≥18 and ≤80 years of age; 2) sepsis according to Sepsis-3; 3) sepsis diagnosis \<48 hours; 4) SIRS; 5) written informed consent from the patient or a legally authorized representative. Exclusion criteria: 1\) Congestive heart failure with NYHA class IV function, cerebrovascular accident or acute coronary syndrome within 3 months, in-hospital or recent (within 7 days) cardiac arrest, non-infectious cardiogenic shock, or uncontrolled acute bleeding; 2) severe chronic liver disease (Child-Pugh C), liver parenchymal disease with significant portal hypertension, or acute liver failure; 3) chronic renal failure with dialysis before enrollment; 4) severe coagulopathy (ISTH DIC score ≥5); 5) significant immune impairment (organ or bone marrow transplantation; moderate or severe leukopenia within 3 months before screening, e.g. neutrophils \<1.5×10\^9/L; radiotherapy or chemotherapy within 3 months; HIV seropositivity; active hematologic or lymphatic malignancy); 6) Xuebijing, thymosin, or gamma globulin within 3 months before enrollment; 7) allergy to study drug, pregnancy, lactation, participation in another clinical trial within 3 months, or other conditions judged by the investigator to preclude participation. Follow-up visits were on days 0, 1, 3, 5, 7, and 28. The primary outcome is the change in Sequential Organ Failure Assessment (SOFA) score from baseline to Day 5 (ΔSOFA). Secondary outcomes include SOFA at other visits, 28-day all-cause mortality, ICU stay, duration of antibiotics, SIRS, vasoactive drugs, mechanical ventilation and CRRT, and laboratory measures of infection, inflammation, coagulation, liver and kidney function, neurological and mental status, and endothelial injury.