Clinical trial NCT01132521: Ulinastatin in Severe Acute Pancreatitis
Official title: Multicenter, Double-bind, Randomised, Placebo Controlled Study of Ulinastatin in Severe Acute Pancreatitis
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE4
Conditions: Pancreatitis
Keywords: ulinastatin
severe acute pancreatitis
Lead sponsor: Techpool Bio-Pharma Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Peking Union Medical College Hospital
name: Wuhan Union Hospital, China
name: The first clinical college of harbin medical university
name: The First Affiliated Hospital with Nanjing Medical University
name: West China Hospital
name: First Affiliated Hospital, Sun Yat-Sen University
First posted: 2010-05-28
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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 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).

Primary outcomes:
measure: multiple organ dysfunction score
timeFrame: 8 days
measure: onset of (multiple) organ failure after randomized
timeFrame: 8 days
Secondary outcomes:
measure: mortality
timeFrame: 8 days, 14 days and 28 days
measure: Incidence of complications
timeFrame: 8 days, 14 days and 28 days
measure: APACHE Ⅱ score
timeFrame: 8 days
measure: Need for surgical intervention
timeFrame: From admission to discharge
measure: Hospital stay and ICU stay
timeFrame: From admission to discharge
measure: CT-scan score
timeFrame: 8 days, 14 days
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Harbin
country: China
facility: The First Clinical College of Harbin University
state: Heilongjiang
city: Wuhan
country: China
facility: Wuhan Union Hospital of China
state: Hubei
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Chengdu
country: China
facility: West China Hospital
state: Sichuan
city: Beijing
country: China
facility: Peking Union Medical College Hospital
Study officials:
affiliation: Peking Union Medical College Hospital
name: Yupei Zhao, MD
role: STUDY_CHAIR
affiliation: Wuhan Union Hospital, China
name: Chunyou Wang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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)
citation: 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.
citation: 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.