Ulinastatin in Severe Acute Pancreatitis

Multicenter, Double-bind, Randomised, Placebo Controlled Study of Ulinastatin in Severe Acute Pancreatitis

This study aims to evaluate the effect of ulinastatin in the treatment and prevention of organ failure in severe acute pancreatitis.

Study Overview

• Status: Suspended
• Conditions: Pancreatitis
• Intervention / Treatment: Drug: ulinastatin; Drug: placebo

Detailed Description

About 20% of patients with acute pancreatitis have a severe course, and 10-15% of those with severe acute pancreatitis (SAP) die. Despite improvements in intensive care treatment during past few decades, effective therapies for acute pancreatitis are still limited.

Early deaths (within the first week) due to severe acute pancreatitis are generally caused by massive inflammatory responses which result in multiple organ failure. Although the exact mechanisms which trigger the inflammatory processes are not completely understood, it is generally accepted that autodigestion and activated leukocytes play important roles in the pathogenesis of acute pancreatitis. Activation of digestive enzymes causes pancreatic injury and results in an inflammatory response that is out of proportion to the response of other organs to a similar insult. The acute inflammatory response itself causes substantial tissue damage and may progress beyond the pancreas to a systemic inflammatory response syndrome, multi organ failure, or death.

UTI is a multivalent Kunitz-type serine protease inhibitor that is found in human urine and blood, it can stabilize lysosome membrane and inhibit lysosome function, inhibit the various enzymes and inflammatory response. Previous study proved that it protects against SIRS pathophysiology and subsequent organ damage induced via the modulation of the proinflammatory mediator, as well as chemokines. UTI has been widely used for the treatment and prevention of multiple organ failure in China, but there is few randomized, placebo controlled trial on ulinastatin. A large multicenter, randomized study is warranted. In this study, we aim to evaluate the effect of ulinastatin in the treatment and prevention of organ failure in severe acute pancreatitis with regular treatment in an add-on trial.

• Study Type: Interventional
• Enrollment (Actual): 252
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Peking Union Medical College Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital of Sun Yat-sen University
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • The First Clinical College of Harbin University
  • Hubei
    • Wuhan, Hubei, China
      • Wuhan Union Hospital of China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of severe acute pancreatitis , severe acute pancreatitis adapted from the Atlanta classification:

Early Prognostic Signs: Ramson signs ≥3, APACHE II score ≥8 Organ Failure and/or Local Complications: Necrosis, Abscess, Pseudocyst;

• Admission within 72h after onset of symptoms of pancreatitis
• 18-70 years old
• Signed the informed consent form

Exclusion Criteria:

• Pre-existing chronic renal insufficiency requiring hemodialysis or peritoneal dialysis
• pre existing heart dysfunction or NYHA classification score above III
• pregnancy or lactation
• Allergy for ulinastatin
• Received an investigational drug or device within 90 days prior to entering study
• serious mentally-ill patients including dementia
• On the verge of death (estimated to be mortal in 12h).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ulinastatin group; Regular treatments plus ulinastatin. Resolved 4 vials of drugs in 100ml physiological saline solution, intravenously infused for 1-2h, tid, for continuous 7 days.	Drug: ulinastatin; Resolved 4 vials of drugs in 100ml physiological saline solution, intravenously infused for 1-2h, tid, for continuous 7 days.; Other Names: UTI; urinary trypsin inhibitor; bikunin
Placebo Comparator: placebo group; Regular treatment plus placebo. Resolved 4 vials of drugs in 100ml physiological saline solution, intravenously infused for 1-2h, tid, for continuous 7 days.	Drug: placebo; Resolved 4 vials of drugs in 100ml physiological saline solution, intravenously infused for 1-2h, tid, for continuous 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
multiple organ dysfunction score	8 days
onset of (multiple) organ failure after randomized	8 days

Secondary Outcome Measures

Outcome Measure	Time Frame
mortality	8 days, 14 days and 28 days
Incidence of complications	8 days, 14 days and 28 days
APACHE Ⅱ score	8 days
Need for surgical intervention	From admission to discharge
Hospital stay and ICU stay	From admission to discharge
CT-scan score	8 days, 14 days

Collaborators and Investigators

• Sponsor: Techpool Bio-Pharma Co., Ltd.
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; Peking Union Medical College Hospital; First Affiliated Hospital, Sun Yat-Sen University; West China Hospital; Wuhan Union Hospital, China; The first clinical college of harbin medical university
• Investigators: Study Chair: Yupei Zhao, MD, Peking Union Medical College Hospital; Principal Investigator: Chunyou Wang, MD, Wuhan Union Hospital, China

Publications and helpful links

General Publications

• Wang CY, Zhao YP. Progress of therapeutic effect in severe acute pancreatitis: Mini-review of treatment viewpoints and technique improvements. Chin J Surg 44(13): 872-4, 2006. (Article in Chinese)
• Maehara K, Kanayama N, Halim A, el Maradny E, Oda T, Fujita M, Terao T. Down-regulation of interleukin-8 gene expression in HL60 cell line by human Kunitz-type trypsin inhibitor. Biochem Biophys Res Commun. 1995 Jan 26;206(3):927-34. doi: 10.1006/bbrc.1995.1131.
• Tsujino T, Komatsu Y, Isayama H, Hirano K, Sasahira N, Yamamoto N, Toda N, Ito Y, Nakai Y, Tada M, Matsumura M, Yoshida H, Kawabe T, Shiratori Y, Omata M. Ulinastatin for pancreatitis after endoscopic retrograde cholangiopancreatography: a randomized, controlled trial. Clin Gastroenterol Hepatol. 2005 Apr;3(4):376-83. doi: 10.1016/s1542-3565(04)00671-8.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2010
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: May 26, 2010
• First Submitted That Met QC Criteria: May 26, 2010
• First Posted (Estimate): May 28, 2010

Study Record Updates

• Last Update Posted (Actual): January 17, 2018
• Last Update Submitted That Met QC Criteria: January 16, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: severe acute pancreatitis; ulinastatin
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Urinastatin; Trypsin Inhibitors
• Other Study ID Numbers: UTI/SAP-S

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided