Thymosin Alpha 1 in the Prevention of Pancreatic Infection Following Acute Necrotizing Pancreatitis

Study Overview
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Brief Summary
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Infected pancreatic necrosis and its related septic complications are the major cause of death in patients with acute pancreatitis, therefore prevention of pancreatic infection is of great clinical value in the treatment of AP. Immunosuppression and disorders characterized by decreased HLA-DR expression and unbalanced CD3/CD4+/CD8+ T cells of PBMC are thought to be associated with the development of pancreatic infection. Thymosin alpha 1 has been shown to have immunomodulatory properties and its effects in preventing pancreatic infection was not well studied. To evaluate the effects of TA1 use in the early phase on preventing pancreatic infection, immunomodulation and clinical outcomes in patients with AP,we aimed to design this study.

Detailed Description
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Study Background & Rationale: Infected pancreatic necrosis and its related septic complications are the major cause of death in patients with acute pancreatitis1, therefore prevention of pancreatic infection is of great clinical value in the treatment of AP. Immunosuppression and disorders characterized by decreased HLA-DR expression and unbalanced CD3/CD4+/CD8+ T cells of PBMC are thought to be associated with the development of pancreatic infection2, 3. Thymosin alpha 1 has been shown to have immunomodulatory properties and its effects in preventing pancreatic infection was not well studied4. Aim of This Study: To evaluate the effects of TA1 use in the early phase on preventing pancreatic infection, immunomodulation and clinical outcomes in patients with AP. Sample Size Estimation: The prevalence of pancreatic infection was reported to be around 25% in AP episodes. To demonstrate a 40% reduction in the prevalence of pancreatic infection with 80% power at a two-sided alpha level of .05, we projected an estimated sample size of 500 participants. Considering possible 2% withdraw, we plan to randomize 510 patients in total.

Official Title
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Thymosin Alpha 1 in the Prevention of Pancreatic Infection Following Acute Necrotizing Pancreatitis

Conditions
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Pancreatitis, Acute Necrotizing

Intervention / Treatment
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* Drug: Thymosin Alpha 1
* Drug: normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Symptoms and signs of acute pancreatitis based on abdominal pain suggestive of AP, serum amylase at least three times the upper limit of normal, and/or characteristic findings of AP on computed tomography or less commonly magnetic resonance imaging (MRI) or transabdominal ultrasonography according to the Revised Atlanta Criteria[15]; Less than one week from the onset of abdominal pain; Age between 18 to 70 years old; Acute Physiology and Chronic Health Evaluation(APACHE II) score ≥8 during the last 24 hours before enrollment Balthazar CT score ≥5 (presence of pancreatic necrosis)[16]. Written informed consent obtained Exclusion criteria Pregnant pancreatitis; History of chronic pancreatitis； Malignancy related acute pancreatitis Receiving early intervention or surgery due to abdominal compartment syndrome or other reasons before admission； Patients with a known history of severe cardiovascular, respiratory, renal or hepatic diseases defined as (1) greater than New York Heart Association Class II heart failure(Class II not included), (2) active myocardial ischemia or (3) cardiovascular intervention within previous 60 days, (4) history of cirrhosis or (5) chronic kidney disease with creatinine clearance< 40 mL/min, or (6) chronic obstructive pulmonary disease with requirement for home oxygen; Patients with preexisting immune disorders such as AIDS.

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thymosin<br>Thymosin alpha 1 has been shown to have immunomodulatory properties | Drug: Thymosin Alpha 1<br>* In addition to the standard treatment, thymosin therapy will be started after admission: 1.6mg I.H q12h for the first 7 days and 1.6mg I.H, qd for the following 7 days or until discharge.<br>* Other names: Thymosin Group;|
| Placebo Comparator: Placebo<br>normal saline; | Drug: normal saline<br>* Placebo inject will be given at the same dose as Thymosin in addition to the standard treatment.<br>* Other names: Placebo Group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of pancreatic infection: |  | during the index admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The occurrence of new-onset organ failure and new-onset persistent organ failure | (SOFA score for respiration, cardiovascular, or renal system ≥2 ). New-onset is defined as events that occur after randomization and not present 24 hours before randomization | during the index admission | 
| In-hospital mortality |  | during the index admission | 
| Bleeding requiring intervention |  | during the index admission | 
| Gastrointestinal perforation or fistula requiring intervention |  | during the index admission | 
| Incidence of pancreatic fistula |  | during the index admission | 
| New receipt of mechanical ventilation/renal replacement therapy /New receipt of vasoactive agents | not applied 24 hours before randomization | during the index admission | 
| The requirement for catheter drainage/Number of drainage procedures required |  | during the index admission | 
| The requirement for minimally-invasive debridement/Number of minimally invasive necrosectomy required |  | during the index admission | 
| The requirement for open surgery/Number of open surgery required |  | during the index admission | 
| Length of intensive care unit(ICU) stay/Length of hospital stay |  | during the index admission | 
| SOFA score/ CRP level/ HLA-DR level/ Lymphocyte count |  | on day0, day7, and day14 | 
| In-hospital cost. |  | during the index admission | 
| Incidence of infection within 90 days after enrollment |  | 90 days after enrollment | 
| Mortality within 90 days after enrollment |  | 90 days after enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Pancreatitis, prevent,Necrotizing