Clinical trial NCT02473406: Thymosin Alpha 1 in the Prevention of Pancreatic Infection Following Acute Necrotizing Pancreatitis
Official title: Thymosin Alpha 1 in the Prevention of Pancreatic Infection Following Acute Necrotizing Pancreatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pancreatitis, Acute Necrotizing
Keywords: Acute Pancreatitis, prevent,Necrotizing
Lead sponsor: Nanjing University School of Medicine
Sponsor class: OTHER
Collaborators: name: The First Affiliated Hospital of Nanchang University
name: The Affiliated Hospital of Qingdao University
name: Zunyi Medical College
name: the Affiliated Nanhua Hospital, University of South China
name: Second Affiliated Hospital of Nantong University
name: Wannan Medical College Yijishan Hospital
name: the 908th Hospital of Chinese People's Liberation Army Joint Logistic Support Force
name: Jiangsu Province Hospital of Traditional Chinese Medicine
name: Zhejiang Provincial People's Hospital
name: Luoyang Central Hospital
name: The Affiliated Hospital of Henan University of Science and Technology
name: Clinical Medical College of Yangzhou University
name: The First People's Hospital of Shangqiu
name: Qilu Hospital of Shandong University
name: The First Affiliated Hospital of Anhui Medical University
First posted: 2015-06-16
Enrollment: 508
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: PREVENTION

Brief summary: 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: 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.

Eligibility 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.

Primary outcomes:
measure: Occurrence of pancreatic infection:
timeFrame: during the index admission
Secondary outcomes:
measure: The occurrence of new-onset organ failure and new-onset persistent organ failure
timeFrame: during the index admission
measure: In-hospital mortality
timeFrame: during the index admission
measure: Bleeding requiring intervention
timeFrame: during the index admission
measure: Gastrointestinal perforation or fistula requiring intervention
timeFrame: during the index admission
measure: Incidence of pancreatic fistula
timeFrame: during the index admission
measure: New receipt of mechanical ventilation/renal replacement therapy /New receipt of vasoactive agents
timeFrame: during the index admission
measure: The requirement for catheter drainage/Number of drainage procedures required
timeFrame: during the index admission
measure: The requirement for minimally-invasive debridement/Number of minimally invasive necrosectomy required
timeFrame: during the index admission
measure: The requirement for open surgery/Number of open surgery required
timeFrame: during the index admission
measure: Length of intensive care unit(ICU) stay/Length of hospital stay
timeFrame: during the index admission
measure: SOFA score/ CRP level/ HLA-DR level/ Lymphocyte count
timeFrame: on day0, day7, and day14
measure: In-hospital cost.
timeFrame: during the index admission
measure: Incidence of infection within 90 days after enrollment
timeFrame: 90 days after enrollment
measure: Mortality within 90 days after enrollment
timeFrame: 90 days after enrollment
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Department of SICU, Research Institute of General Surgery Jinling Hospital, Nanjing, Jiangsu, China
state: Jiangsu
city: Nanjing
country: China
facility: Jinling Hospital
state: Jiangsu
Study officials:
affiliation: Department of SICU, Research Institute of General Surgery Jinling Hospital, Nanjing, Jiangsu, Chin
name: Li Weiqin, M.D.
role: STUDY_CHAIR
affiliation: Department of SICU, Research Institute of General Surgery Jinling Hospital, Nanjing, Jiangsu, Chin
name: Ke Lu, M.D.
role: STUDY_DIRECTOR
affiliation: Department of SICU, Research Institute of General Surgery Jinling Hospital, Nanjing, Jiangsu, Chin
name: Zhou Jing, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhou J, Mao W, Ke L, Chen T, He W, Pan X, Chen M, He C, Gu W, Wu J, Song J, Ni H, Tu J, Sun J, Zhang G, Chen W, Xue B, Zhao X, Shao M, Liu Y, Tong Z, Li W; Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG). Thymosin alpha 1 in the prevention of infected pancreatic necrosis following acute necrotising pancreatitis (TRACE trial): protocol of a multicentre, randomised, double-blind, placebo-controlled, parallel-group trial. BMJ Open. 2020 Sep 29;10(9):e037231. doi: 10.1136/bmjopen-2020-037231.