Efficacy and Safety of Intravenous Ulinastatin versus Placebo along with Standard Supportive Care in Subjects with Mild or Severe Acute Pancreatitis

摘要

Background: Ulinastatin is reported to inhibit pro-inflammatory markers and also inhibits coagulation and fibrinolysis. The drug is available in East Asia for the treatment of acute pancreatitis. Aim: To study the effect of addition of ulinastatin to standard care on mortality and morbidity in Indian subjects with acute pancreatitis.Design: Randomized, double-blind, placebo-controlled, multi-centre trial across 15 centres in India.Methods: Subjects, aged 18 to 70 years, with acute pancreatitis and elevated serum C-reactive protein (CRP) levels, were eligible for enrolment. Acute pancreatitis was diagnosed if the patient had at least two of the following criteria: suggestive abdominal pain, serum amylase and/or lipase >3 times upper limit of normal, and imaging findings of acute pancreatitis. Subjects were classified as having mild or severe acute pancreatitis on the basis of the APACHE II score (Results: Of 135 randomized subjects, 129 completed the study (mild 62, severe 67). Pancreatitis was due to alcohol intake in a majority (81%) of subjects. Baseline characteristics were similar between the ulinastatin and placebo groups. Efficacy was evaluated in subjects who had received at least 3 days (6 doses) of ulinastatin / placebo. One subject with severe pancreatitis in the ulinastatin group versus six in the placebo group died (p=0.048). New organ dysfunction developed in 5 ulinastatin vs 4 placebo group subjects (p=0.744) with mild pancreatitis and 12 ulinastatin vs 29 placebo group subjects (p=0.0026) with severe pancreatitis. Adverse events were significantly lower in subjects with severe pancreatitis in the ulinastatin group as compared to the placebo group (p=0.00001). Reduction in serum CRP was not different between the groups. Median hospitalization was shorter by one day in the ulinastatin group; the difference was not significant. There was no infusion-related adverse event.Conclusions: Ulinastatin prevents new organ dysfunction and reduces mortality in subjects with severe pancreatitis