Efficacy and safety of intravenous ulinastatin versus placebo along with standard supportive care in subjects with mild or severe acute pancreatitis.

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.To study the effect of addition of ulinastatin to standard care on mortality and morbidity in Indian subjects with acute pancreatitis.Randomized, double-blind, placebo-controlled, multi-centre trial across 15 centres in India.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 (< 8 mild, > or = 8 severe). Standard care was given to all subjects as per the treating physician's protocol. Eligible subjects were randomized to receive intravenous infusion of 200,000 IU ulinastatin or placebo in 100 mL of 0.9% saline given over one hour every 12 hours for 5 days.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.Ulinastatin prevents new organ dysfunction and reduces mortality in subjects with severe pancreatitis.