Ulinastatin in Severe Acute Pancreatitis

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

Detailed Description
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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.

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

Conditions
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Pancreatitis

Intervention / Treatment
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* Drug: ulinastatin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ulinastatin group<br>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<br>* Resolved 4 vials of drugs in 100ml physiological saline solution, intravenously infused for 1-2h, tid, for continuous 7 days.<br>* Other names: bikunin;|
| Placebo Comparator: placebo group<br>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<br>* Resolved 4 vials of drugs in 100ml physiological saline solution, intravenously infused for 1-2h, tid, for continuous 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ulinastatin, severe acute pancreatitis