Ulinastatin in Severe Acute Pancreatitis

This study has suspended participant recruitment.
(Revised project)
Sponsor:
Collaborators:
Peking Union Medical College Hospital
Wuhan Union Hospital, China
The first clinical college of harbin medical university
The First Affiliated Hospital with Nanjing Medical University
West China Hospital
First Affiliated Hospital, Sun Yat-Sen University
Information provided by (Responsible Party):
Techpool Bio-Pharma Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01132521
First received: May 26, 2010
Last updated: June 27, 2016
Last verified: June 2016
  Purpose
This study aims to evaluate the effect of ulinastatin in the treatment and prevention of organ failure in severe acute pancreatitis.

Condition Intervention Phase
Pancreatitis
Drug: ulinastatin
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multicenter, Double-bind, Randomised, Placebo Controlled Study of Ulinastatin in Severe Acute Pancreatitis

Resource links provided by NLM:


Further study details as provided by Techpool Bio-Pharma Co., Ltd.:

Primary Outcome Measures:
  • multiple organ dysfunction score [ Time Frame: 8 days ] [ Designated as safety issue: No ]
  • onset of (multiple) organ failure after randomized [ Time Frame: 8 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • mortality [ Time Frame: 8 days, 14 days and 28 days ] [ Designated as safety issue: No ]
  • Incidence of complications [ Time Frame: 8 days, 14 days and 28 days ] [ Designated as safety issue: No ]
  • APACHE Ⅱ score [ Time Frame: 8 days ] [ Designated as safety issue: No ]
  • Need for surgical intervention [ Time Frame: From admission to discharge ] [ Designated as safety issue: No ]
  • Hospital stay and ICU stay [ Time Frame: From admission to discharge ] [ Designated as safety issue: No ]
  • CT-scan score [ Time Frame: 8 days, 14 days ] [ Designated as safety issue: No ]

Enrollment: 252
Study Start Date: June 2010
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01132521

Locations
China, Guangdong
The First Affiliated Hospital of Sun Yat-Sen University
Guangzhou, Guangdong, China
China, Heilongjiang
The First Clinical College of Harbin University
Harbin, Heilongjiang, China
China, Hubei
Wuhan Union Hospital of China
Wuhan, Hubei, China
China, Jiangsu
Jiangsu Province Hospital
Nanjing, Jiangsu, China
China, Sichuan
West China Hospital
Chengdu, Sichuan, China
China
Peking Union Medical College Hospital
Beijing, China
Sponsors and Collaborators
Techpool Bio-Pharma Co., Ltd.
Peking Union Medical College Hospital
Wuhan Union Hospital, China
The first clinical college of harbin medical university
The First Affiliated Hospital with Nanjing Medical University
West China Hospital
First Affiliated Hospital, Sun Yat-Sen University
Investigators
Study Chair: Yupei Zhao, MD Peking Union Medical College Hospital
Principal Investigator: Chunyou Wang, MD Wuhan Union Hospital, China
  More Information

Additional Information:
Publications:
Responsible Party: Techpool Bio-Pharma Co., Ltd.
ClinicalTrials.gov Identifier: NCT01132521     History of Changes
Other Study ID Numbers: UTI/SAP-S 
Study First Received: May 26, 2010
Last Updated: June 27, 2016
Health Authority: China: Ethics Committee
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Techpool Bio-Pharma Co., Ltd.:
ulinastatin
severe acute pancreatitis

Additional relevant MeSH terms:
Pancreatitis
Pancreatic Diseases
Digestive System Diseases
Urinastatin
Trypsin Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 29, 2016