Ulinastatin in Severe Acute Pancreatitis

Techpool Bio-Pharma

Status and phase: Suspended; Phase 4

Conditions: Pancreatitis

Treatments: Drug: ulinastatin; Drug: placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01132521

UTI/SAP-S

Details and patient eligibility

About

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

Full 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.

Enrollment: 252 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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252 participants in 2 patient groups, including a placebo group

ulinastatin group

Experimental group

Description:

Regular treatments plus ulinastatin. Resolved 4 vials of drugs in 100ml physiological saline solution, intravenously infused for 1-2h, tid, for continuous 7 days.

Treatment:

Drug: ulinastatin

placebo group

Placebo Comparator group

Description:

Regular treatment plus placebo. Resolved 4 vials of drugs in 100ml physiological saline solution, intravenously infused for 1-2h, tid, for continuous 7 days.

Treatment:

Drug: placebo