Randomized Controlled Trial

. 2022 Jul;48(7):899-909.

doi: 10.1007/s00134-022-06745-7. Epub 2022 Jun 17.

Immune enhancement in patients with predicted severe acute necrotising pancreatitis: a multicentre double-blind randomised controlled trial

Lu Ke^#^{1

2}, Jing Zhou^#^{1

3}, Wenjian Mao^#³, Tao Chen⁴, Yin Zhu⁵, Xinting Pan⁶, Hong Mei⁷, Vikesh Singh⁸, James Buxbaum⁹, Gordon Doig¹⁰, Chengjian He¹¹, Weili Gu¹², Weihua Lu¹³, Shumin Tu¹⁴, Haibin Ni¹⁵, Guoxiu Zhang¹⁶, Xiangyang Zhao¹⁷, Junli Sun¹⁸, Weiwei Chen¹⁹, Jingchun Song²⁰, Min Shao²¹, Jianfeng Tu²², Liang Xia⁵, Wenhua He⁵, Qingyun Zhu⁶, Kang Li⁷, Hongyi Yao¹¹, Jingyi Wu¹³, Long Fu¹⁴, Wendi Jiang¹, He Zhang²³, Jiajia Lin¹, Baiqiang Li¹, Zhihui Tong²⁴, John Windsor²⁵, Yuxiu Liu^{1

26}, Weiqin Li^{27

28

29}; Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG)

Collaborators, Affiliations

Collaborators

Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG):
Lu Ke, Jing Zhou, Wenjian Mao, Wendi Jiang, He Zhang, Jiajia Lin, Mingfeng Huang, Longxiang Cao, Mengjie Lu, Yan Chen, Gang Li, Bo Ye, Baiqiang Li, Zhihui Tong, Yuxiu Liu, Weiqin Li, Tao Chen, Fang Shao, Nonghua Lv, Yin Zhu, Liang Xia, Wenhua He, Zhenping Chen, Xinting Pan, Qingyun Zhu, Youdong Wan, Hong Mei, Kang Li, Miao Chen, Chengjian He, Hongyi Yao, Zigui Zhu, Weili Gu, Weihua Lu, Jingyi Wu, Feng Zhou, Shumin Tu, Long Fu, Bing Xue, Haibin Ni, Xiaofei Huang, Dandan Zhou, Guoxiu Zhang, Lening Ren, Dahuan Li, Xiangyang Zhao, Wei Zhao, Xiaomei Chen, Junli Sun, Keke Xin, Weiwei Chen, Qingcheng Xu, Jingchun Song, Qingbo Zeng, Min Shao, Dongsheng Zhao, Jianfeng Tu, Hongguo Yang, Bin Wu, Huaguang Ye, Mingzhi Chen, Yingjie Chen, Mei Yang, Hong Gao, Qiang Li, Lijuan Zhao, Guobing Chen, Yafei Li, Honghai Xia, Dongliang Yang, Shusheng Zhou, Jiyan Lin, Siyao Liu, Donghuang Hong, Songjing Shi, Zuozheng Wang, Weijie Yao, Yi Sun, Kaixiu Qin, Shan Xu, Lei Yu, Feng Guo, Yongjun Lin, Yun Zhou, Qinghai Jiao, Quanxing Feng, Zhiyong Li

Affiliations

¹ Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, 210000, Jiangsu, China.
² National Institute of Healthcare Data Science, Nanjing University, Nanjing, 210010, Jiangsu, China.
³ Department of Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, 210010, Jiangsu, China.
⁴ Department of Public Health, Policy and Systems, Institute of Population Health, Whelan Building, Quadrangle, The University of Liverpool, Liverpool, L69 3GB, UK.
⁵ Pancreatic Disease Centre, Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
⁶ Department of Emergency Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China.
⁷ Department of Critical Care Medicine, The Affiliated Hospital of Zunyi Medical University, Zunyi, 536000, Guizhou, China.
⁸ Pancreatitis Centre, Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
⁹ Division of Gastroenterology, Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, USA.
¹⁰ Northern Clinical School, Royal, North Shore Hospital, University of Sydney, Sydney, Australia.
¹¹ Department of Critical Care Medicine, the Affiliated Nanhua Hospital, University of South China, Hengyang, 421002, Hunan, China.
¹² Department of Critical Care Medicine, Affiliated Hospital 2 of Nantong University, Nantong, 226000, Jiangsu, China.
¹³ Department of Intensive Care Unit, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China.
¹⁴ Department of Emergency Medicine, Shangqiu First People's Hospital, Shangqiu, 476000, Henan, China.
¹⁵ Department of Emergency Medicine, Jiangsu Provincial Hospital of Integrated Chinese and Western Medicine, Nanjing, 210010, Jiangsu, China.
¹⁶ Department of Emergency Medicine, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, Henan, China.
¹⁷ Department of Intensive Care Unit, Qilu Hospital of Shandong University, Qingdao, 266000, Shandong, China.
¹⁸ Department of Intensive Care Unit, Luoyang Central Hospital, Zhengzhou University, Luoyang, 471100, Henan, China.
¹⁹ Department of Gastroenterology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China.
²⁰ Department of Critical Care Medicine, 94Th Hospital of PLA, Nanchang, 330006, Jiangxi, China.
²¹ Department of Intensive Care Unit, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.
²² Department of Emergency Medicine, Zhejiang Provincial People's Hospital, Hangzhou, 310014, Zhejiang, China.
²³ Department of Critical Care Medicine, Jinling Hospital, Medical School of Southeast University, Nanjing, 210002, Jiangsu, China.
²⁴ Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, 210000, Jiangsu, China. njzyantol@aliyun.com.
²⁵ Surgical and Translational Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, 1142, New Zealand.
²⁶ Department of Medical Statistics, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China.
²⁷ Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, 210000, Jiangsu, China. ctgchina@medbit.cn.
²⁸ Department of Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, 210010, Jiangsu, China. ctgchina@medbit.cn.
²⁹ National Institute of Healthcare Data Science, Nanjing University, Nanjing, 210010, Jiangsu, China. ctgchina@medbit.cn.

^# Contributed equally.

PMID: 35713670
PMCID: PMC9205279
DOI: 10.1007/s00134-022-06745-7

Randomized Controlled Trial

Immune enhancement in patients with predicted severe acute necrotising pancreatitis: a multicentre double-blind randomised controlled trial

Lu Ke et al. Intensive Care Med. 2022 Jul.

. 2022 Jul;48(7):899-909.

doi: 10.1007/s00134-022-06745-7. Epub 2022 Jun 17.

Authors

Collaborators

Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG):
Lu Ke, Jing Zhou, Wenjian Mao, Wendi Jiang, He Zhang, Jiajia Lin, Mingfeng Huang, Longxiang Cao, Mengjie Lu, Yan Chen, Gang Li, Bo Ye, Baiqiang Li, Zhihui Tong, Yuxiu Liu, Weiqin Li, Tao Chen, Fang Shao, Nonghua Lv, Yin Zhu, Liang Xia, Wenhua He, Zhenping Chen, Xinting Pan, Qingyun Zhu, Youdong Wan, Hong Mei, Kang Li, Miao Chen, Chengjian He, Hongyi Yao, Zigui Zhu, Weili Gu, Weihua Lu, Jingyi Wu, Feng Zhou, Shumin Tu, Long Fu, Bing Xue, Haibin Ni, Xiaofei Huang, Dandan Zhou, Guoxiu Zhang, Lening Ren, Dahuan Li, Xiangyang Zhao, Wei Zhao, Xiaomei Chen, Junli Sun, Keke Xin, Weiwei Chen, Qingcheng Xu, Jingchun Song, Qingbo Zeng, Min Shao, Dongsheng Zhao, Jianfeng Tu, Hongguo Yang, Bin Wu, Huaguang Ye, Mingzhi Chen, Yingjie Chen, Mei Yang, Hong Gao, Qiang Li, Lijuan Zhao, Guobing Chen, Yafei Li, Honghai Xia, Dongliang Yang, Shusheng Zhou, Jiyan Lin, Siyao Liu, Donghuang Hong, Songjing Shi, Zuozheng Wang, Weijie Yao, Yi Sun, Kaixiu Qin, Shan Xu, Lei Yu, Feng Guo, Yongjun Lin, Yun Zhou, Qinghai Jiao, Quanxing Feng, Zhiyong Li

Affiliations

¹ Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, 210000, Jiangsu, China.
² National Institute of Healthcare Data Science, Nanjing University, Nanjing, 210010, Jiangsu, China.
³ Department of Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, 210010, Jiangsu, China.
⁴ Department of Public Health, Policy and Systems, Institute of Population Health, Whelan Building, Quadrangle, The University of Liverpool, Liverpool, L69 3GB, UK.
⁵ Pancreatic Disease Centre, Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
⁶ Department of Emergency Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China.
⁷ Department of Critical Care Medicine, The Affiliated Hospital of Zunyi Medical University, Zunyi, 536000, Guizhou, China.
⁸ Pancreatitis Centre, Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
⁹ Division of Gastroenterology, Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, USA.
¹⁰ Northern Clinical School, Royal, North Shore Hospital, University of Sydney, Sydney, Australia.
¹¹ Department of Critical Care Medicine, the Affiliated Nanhua Hospital, University of South China, Hengyang, 421002, Hunan, China.
¹² Department of Critical Care Medicine, Affiliated Hospital 2 of Nantong University, Nantong, 226000, Jiangsu, China.
¹³ Department of Intensive Care Unit, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China.
¹⁴ Department of Emergency Medicine, Shangqiu First People's Hospital, Shangqiu, 476000, Henan, China.
¹⁵ Department of Emergency Medicine, Jiangsu Provincial Hospital of Integrated Chinese and Western Medicine, Nanjing, 210010, Jiangsu, China.
¹⁶ Department of Emergency Medicine, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, Henan, China.
¹⁷ Department of Intensive Care Unit, Qilu Hospital of Shandong University, Qingdao, 266000, Shandong, China.
¹⁸ Department of Intensive Care Unit, Luoyang Central Hospital, Zhengzhou University, Luoyang, 471100, Henan, China.
¹⁹ Department of Gastroenterology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China.
²⁰ Department of Critical Care Medicine, 94Th Hospital of PLA, Nanchang, 330006, Jiangxi, China.
²¹ Department of Intensive Care Unit, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.
²² Department of Emergency Medicine, Zhejiang Provincial People's Hospital, Hangzhou, 310014, Zhejiang, China.
²³ Department of Critical Care Medicine, Jinling Hospital, Medical School of Southeast University, Nanjing, 210002, Jiangsu, China.
²⁴ Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, 210000, Jiangsu, China. njzyantol@aliyun.com.
²⁵ Surgical and Translational Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, 1142, New Zealand.
²⁶ Department of Medical Statistics, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China.
²⁷ Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, 210000, Jiangsu, China. ctgchina@medbit.cn.
²⁸ Department of Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, 210010, Jiangsu, China. ctgchina@medbit.cn.
²⁹ National Institute of Healthcare Data Science, Nanjing University, Nanjing, 210010, Jiangsu, China. ctgchina@medbit.cn.

^# Contributed equally.

PMID: 35713670
PMCID: PMC9205279
DOI: 10.1007/s00134-022-06745-7

Abstract

Purpose: Infected pancreatic necrosis (IPN) is a highly morbid complication of acute necrotising pancreatitis (ANP). Since there is evidence of early-onset immunosuppression in acute pancreatitis, immune enhancement may be a therapeutic option. This trial aimed to evaluate whether early immune-enhancing Thymosin alpha 1 (Tα1) treatment reduces the incidence of IPN in patients with predicted severe ANP.

Methods: We conducted a multicentre, double-blind, randomised, placebo-controlled trial involving ANP patients with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 8 and a computed tomography (CT) severity score ≥ 5 admitted within 7 days of the advent of symptoms. Enrolled patients were assigned to receive a subcutaneous injection of Tα1 1.6 mg every 12 h for the first 7 days and 1.6 mg once a day for the subsequent 7 days or matching placebos (normal saline). The primary outcome was the development of IPN during the index admission.

Results: A total of 508 patients were randomised, of whom 254 were assigned to receive Tα1 and 254 placebo. The vast majority of the participants required admission to the intensive care unit (ICU) (479/508, 94.3%). During the index admission, 40/254(15.7%) patients in the Tα1 group developed IPN compared with 46/254 patients (18.1%) in the placebo group (difference -2.4% [95% CI - 7.4 to 5.1%]; p = 0.48). The results were similar across four predefined subgroups. There was no difference in other major complications, including new-onset organ failure (10.6% vs. 15%), bleeding (6.3% vs. 3.5%), and gastrointestinal fistula (2% vs. 2.4%).

Conclusion: The immune-enhancing Tα1 treatment of patients with predicted severe ANP did not reduce the incidence of IPN during the index admission.

Keywords: Acute pancreatitis; Immunosuppression; Infection; Pancreatic necrosis; Thymosin.

PubMed Disclaimer

Conflict of interest statement

WL reports consultancy fees and grants from SciClone Pharmaceuticals. ZT reports speaker fees from SciClone Pharmaceuticals. LK reports speaker fees from SciClone Pharmaceuticals. VS reports consultant fees and grants Abbvie, medical advisory board participant for Envara, and grants from Theraly and Orgenesis. The other authors have no relevant conflict of interest to declare.

Figures

**Fig. 1**
Enrolment, randomisation, and follow-up of patients in the TRACE trial. TRACE denotes thymosin α1 in prevention of infected pancreatic necrosis following acute necrotising pancreatitis. APACHE II denotes acute physiology and chronic health evaluation II. CTSI denotes computed tomography severity index. ITT denotes intention to treat. Tα1 denotes Thymosin α1

**Fig. 2**
Time- to-infection by day 90. The Kaplan–Meier curves for the cumulative incidence of infected pancreatic necrosis from randomisation to day 90 in the intention-to-treat population

**Fig. 3**
Subgroup analysis of the risk of infected pancreatic necrosis by the index hospital discharge and day 90. Panel A shows the risk difference of infected pancreatic necrosis during the index admission between the two treatment groups. Panel B shows the risk difference of infected pancreatic necrosis up to 90 days after randomisation. A risk difference of less than 0 indicates better results for the Tα1 group

See this image and copyright information in PMC

References

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Immune enhancement in patients with predicted severe acute necrotising pancreatitis: a multicentre double-blind randomised controlled trial

Collaborators

Affiliations

Immune enhancement in patients with predicted severe acute necrotising pancreatitis: a multicentre double-blind randomised controlled trial

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

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