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

Weiqin Li

Status and phase: Completed; Phase 4

Conditions: Pancreatitis, Acute Necrotizing

Treatments: Drug: normal saline; Drug: Thymosin Alpha 1

Study type: Interventional

Funder types: Other

Identifiers

NCT02473406

TRACE trial

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 508 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

1. 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];
2. Less than one week from the onset of abdominal pain;
3. Age between 18 to 70 years old;
4. Acute Physiology and Chronic Health Evaluation(APACHE II) score ≥8 during the last 24 hours before enrollment
5. Balthazar CT score ≥5 (presence of pancreatic necrosis)[16].
6. Written informed consent obtained

Exclusion criteria

1. Pregnant pancreatitis;
2. History of chronic pancreatitis；
3. Malignancy related acute pancreatitis
4. Receiving early intervention or surgery due to abdominal compartment syndrome or other reasons before admission；
5. 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;
6. Patients with preexisting immune disorders such as AIDS.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

508 participants in 2 patient groups, including a placebo group

Thymosin

Experimental group

Description:

Thymosin alpha 1 has been shown to have immunomodulatory properties

Treatment:

Drug: Thymosin Alpha 1

Placebo

Placebo Comparator group

Description:

normal saline;

Treatment:

Drug: normal saline