BMJ Open (Apr 2025)
Endoscopic variceal ligation combined with carvedilol versus endoscopic variceal ligation combined with propranolol for the treatment of oesophageal variceal bleeding in cirrhosis: study protocol for a multicentre, randomised controlled trial
- Jing Wang,
- Meng Li,
- Lei Wang,
- Li Zhang,
- Ling Yang,
- Jian Wang,
- Duolao Wang,
- Rong Wang,
- Ya Peng,
- Chao Ma,
- Yiling Li,
- Yi Chen,
- Jing Xu,
- Xiaolong Qi,
- Hua Ye,
- Zhendong Jin,
- Hongyun Zhao,
- Wei Yan,
- Liwei Zhang,
- Chuan Liu,
- Andres Cardenas,
- Li Du,
- Ying Song,
- Biao Xie,
- Zhi Wei,
- Jianzhou Li,
- Wenhui Zhang,
- Qinghua Pan,
- Huiling Xiang,
- Shaoting Zhang,
- Shuairan Zhang,
- Xuan Liang,
- Shengjuan Hu,
- Lijun Peng,
- Xiaojie Zhang,
- Jingyi Xu,
- Xiaochao Liu,
- Huanhai Xu,
- Zhixu Fan,
- Lichun Shao,
- Pengyuan He,
- Qianlong Li,
- Yunhai Wu,
- Liyao Zhang,
- Dianliang Fang,
- Quanke Li,
- Dongli Xia,
- Yuchen Lv,
- Zongchao Zhang,
- Chaoguang Yan,
- Yuxia Wan,
- Haiming Fang,
- Wenlong Yang,
- Xiangman Zhang,
- Wei Rao,
- Xiurong Xia,
- Qiang Qiao,
- Ruimiao Yu,
- Changzhen Ren,
- Yuejun Yang,
- Zhenzhen Zhai,
- Xuejin Liu,
- Xingjun Lu,
- Yansheng Jia
Affiliations
- Jing Wang
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
- Meng Li
- NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, National Institutes for Food and Drug Control, Beijing, China
- Lei Wang
- 3 Outpatient Department Office, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Li Zhang
- Fujian Provincial Hospital, Fuzhou, China
- Ling Yang
- He Eye Specialist Hospital, Shenyang, China
- Jian Wang
- Department of Neurology, The Second People’s Hospital, Chengdu, Sichuan, China
- Duolao Wang
- professor
- Rong Wang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Ya Peng
- Department of Neurosurgery, Changzhou First People`s Hospital, Changzhou, Jiangsu, China
- Chao Ma
- 5 Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of MedicalSciences and Peking Union Medical College, Beijing, China
- Yiling Li
- 4 Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, Liaoning, China
- Yi Chen
- 2 Guangxi Academy of Medical Sciences & The People`s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
- Jing Xu
- 4 Centre for Quantitative Medicine, Duke-NUS Graduate Medical School, Singapore
- Xiaolong Qi
- 1 State Key Laboratory of Digital Medical Engineering, Department of Radiology, Zhongda Hospital, Southeast University, Nanjing, China
- Hua Ye
- Department of Rheumatology and Immunology, Peking University People’s Hospital, China
- Zhendong Jin
- Department of Gastroenterology, Naval Medical University, Shanghai, China
- Hongyun Zhao
- 1Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
- Wei Yan
- 6Sound Biologics, Bothell, WA, USA
- Liwei Zhang
- Department of Neurosurgery, Beijing Tiantan Hospital, Beijing, China
- Chuan Liu
- 1 Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, Jiangsu, China
- Andres Cardenas
- 3 Department of Epidemiology and Population Health, Stanford University, Stanford, California, USA
- Li Du
- Department of Anesthesiology, Sichuan Cancer Hospital and Research Institute, Chengdu, Sichuan, China
- Ying Song
- 1Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
- Biao Xie
- Department of Biostatistics, Chongqing Medical University, Chongqing, Sichuan, China
- Zhi Wei
- Department of Gastroenterology, Shandong Second Provincial General Hospital, Jinan, Shandong, China
- Jianzhou Li
- 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Wenhui Zhang
- Pain Medicine, Harbin Medical University Cancer Hospital, Harbin, China
- Qinghua Pan
- Department of Ophthalmology and Otorhinolaryngology, The Second People’s Hospital of Xiangtan City, Xiangtan, Hunan, China
- Huiling Xiang
- 8Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
- Shaoting Zhang
- Department of Anesthesiology, Guangdong Provincial People`s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Shuairan Zhang
- 4 Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, Liaoning, China
- Xuan Liang
- 7 Shenyang Sixth People’s Hospital, Shenyang, Liaoning, China
- Shengjuan Hu
- 10 Department of Gastroenterology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia, China
- Lijun Peng
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
- Xiaojie Zhang
- 1 Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/ National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Jingyi Xu
- College of Stomatology, Chongqing Medical University, Chongqing, China
- Xiaochao Liu
- Department of Gastroenterology, Hanzhong Central Hospity, Hanzhong, China
- Huanhai Xu
- Department of Gastroenterology, Affiliated Yueqing Hospital of Wenzhou Medical University, Yueqing, China
- Zhixu Fan
- Department of Gastroscope, The Sixth People’s Hospital of Dandong, Dandong, Liaoning, China
- Lichun Shao
- Department of Gastroenterology, Air Force Hospital of Northern Theater Command, Shenyang, Liaoning, China
- Pengyuan He
- Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China
- Qianlong Li
- Department of Gastroenterology, Suining Central Hospital, Suining, China
- Yunhai Wu
- The Sixth People’s Hospital of Shenyang, Shenyang, Liaoning, China
- Liyao Zhang
- The Sixth People’s Hospital of Shenyang, Shenyang, Liaoning, China
- Dianliang Fang
- Department of Gastroenterology, The Fourth People’s Hospital of Chongqing, Chongqing, China
- Quanke Li
- Department of Gastroenterology, Anqiu People’s Hospital, Weifang, Shandong, China
- Dongli Xia
- Department of Gastroenterology, Fuling Hospital affiliated to Chongqing University, Chongqing, China
- Yuchen Lv
- Medical Department, Qingdao Third People’s Hospital, Qingdao, Shandong, China
- Zongchao Zhang
- Department of Hepatology, The Fifth Hospital of Xingtai, Xingtai, Hebei, China
- Chaoguang Yan
- Department of Gastroenterology, Second People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
- Yuxia Wan
- Department of Endoscopy, Qianwei People’s Hospital, Leshan, Sichuan, China
- Haiming Fang
- Department of Gastroenterology, Pingshan Hospital of Southern Medical University, Shenzhen, China
- Wenlong Yang
- Department of Infectious Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Xiangman Zhang
- Suzhou Hengrui Medical Devices Co., Ltd, Suzhou, China
- Wei Rao
- Shenzhen New Industries Biomedical Engineering Co Ltd, Shenzhen, Guangdong, China
- Xiurong Xia
- Emergency Department, The Affiliated Qingdao Third People’s Hospital of Qingdao University, Qingdao, China
- Qiang Qiao
- Department of Gastroenterology, Ansteel Group General Hospital, Anshan, China
- Ruimiao Yu
- Department of Gastroenterology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia, China
- Changzhen Ren
- Department of Infectious Diseases, Zibo Central Hospital, Zibo, Shandong, China
- Yuejun Yang
- 8. Department of Gastroenterology, GongRen Hospital of WuZhou, Wuzhou, Guangxi, China
- Zhenzhen Zhai
- Department of Gastroenterology, Qilu Hospital of Shandong University Dezhou Hospital, Nanjing, Jiangsu, China
- Xuejin Liu
- Department of Gastroenterology, Zhoukou Central Hospital, Zhoukou, China
- Xingjun Lu
- Department of Gastroenterology, The Peoples’ Hospital of Bozhou, Bozhou, China
- Yansheng Jia
- Department of Endoscopy, The Fifth Hospital of Shijiazhuang, Shijiazbuang, Hebei, China
- DOI
- https://doi.org/10.1136/bmjopen-2024-093866
- Journal volume & issue
-
Vol. 15,
no. 4
Abstract
Introduction Liver cirrhosis and its severe complication, oesophageal variceal bleeding (EVB), pose significant health risks. Standard treatment for EVB combines non-selective beta-blockers (NSBB) with endoscopic variceal ligation (EVL). Carvedilol, an NSBB with additional benefits, is preferred for compensated cirrhosis. However, no randomised controlled trial (RCT) has compared carvedilol with propranolol, a conventional NSBB, in combination with EVL for secondary prophylaxis. This study aims to compare the effectiveness and safety of these treatments in preventing variceal rebleeding or death in patients with cirrhosis and EVB.Methods and analysis This multicentre, RCT is scheduled to begin in December 2024, with recruitment and follow-up continuing until December 2026. Eligible participants are patients with liver cirrhosis and EVB. Participants are randomly assigned in a 1:1 ratio to receive EVL combined with either carvedilol or propranolol. The primary endpoint is the incidence of variceal rebleeding or all-cause death. Secondary endpoints include all-cause death, liver-related death, each of the complications of portal hypertension (overt ascites, overt hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, portal vein thrombosis), hepatocellular carcinoma, changes in liver function (assessed by Child-Pugh and Model for End-Stage Liver Disease scores), changes in liver stiffness, changes in spleen stiffness, and adverse events. Subgroup and sensitivity analyses will be conducted to evaluate the consistency and robustness of the treatment effects. A total sample size of 524 patients (262 per group) is required to detect a significant difference between the treatment arms.Ethics and dissemination The study protocol has been approved by the ethics committee of the First Hospital of China Medical University (No. 2024-656-2). The study will follow the Declaration of Helsinki and Good Clinical Practice guidelines. The findings of this trial will be disseminated through peer-reviewed publications, conference presentations and healthcare professionals to guide future clinical practice.Trial registration number Chinese Clinical Trial Registry (Registration number: ChiCTR2400089692).
