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Carvedilol to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by liver stiffness: study protocol for a randomied, double-blind, placebo-controlled, multicentre trial in China

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机构: [1]Southeast Univ, Med Sch, Zhongda Hosp, Ctr Portal Hypertens,Dept Radiol,Nurturing Ctr Jia, Nanjing, Jiangsu, Peoples R China [2]Southeast Univ, Zhongda Hosp, Basic Med Res & Innovat Ctr, Minist Educ,State Key Lab Digital Med Engn, Nanjing, Peoples R China [3]Lanzhou Univ, Portal Hypertens Res Inst, Dept Hepatol, Hosp 1, Lanzhou, Gansu, Peoples R China [4]China Med Univ, Dept Gastroenterol, Hosp 1, Shenyang, Liaoning, Peoples R China [5]Changi Gen Hosp, Dept Gastroenterol & Hepatol, Singapore, Singapore [6]Duke NUS Med Sch, Singapore, Singapore [7]Shenyang Sixth Peoples Hosp, Shenyang, Liaoning, Peoples R China [8]Qingdao Sixth Peoples Hosp, Qingdao, Shandong, Peoples R China [9]Lishui Peoples Hosp, Lishui, Zhejiang, Peoples R China [10]Peoples Hosp Ningxia Hui Autonomous Reg, Dept Gynecol, Yinchuan, Ningxia, Peoples R China [11]Peoples Liberat Army Gen Hosp, Dept Infect Dis, Med Ctr 5, Beijing, Peoples R China [12]Zhenjiang Third Peoples Hosp, Zhenjiang, Jiangsu, Peoples R China [13]Zhuhai Third Peoples Hosp, Zhuhai, Guangdong, Peoples R China [14]Shenzhen Peoples Hosp, Shenzhen, Guangdong, Peoples R China [15]Xingtai Peoples Hosp, Dept Infect Dis, Xingtai, Hebei, Peoples R China [16]Sichuan Univ, Huaxi Hosp, Tibet Chengban Branch, Chengdu, Sichuan, Peoples R China [17]Hubei Univ Med, Taihe Hosp, Inst Biomed Res, Hubei Prov Clin Res Ctr Precise Diag & Treatment L, Shiyan, Hubei, Peoples R China [18]Hubei Univ Med, Taihe Hosp, Hubei Key Lab Embryon Stem Cell Res, Shiyan, Hubei, Peoples R China [19]Hubei Univ Med, Taihe Hosp, Dept Infect Dis, Shiyan, Hubei, Peoples R China [20]Third Peoples Hosp Tibet Autonomous Reg, Lhasa, Tibet, Peoples R China [21]Handan Infect Dis Hosp, Handan, Hebei, Peoples R China [22]Qinhuangdao Third Hosp, Qinhuangdao, Hebei, Peoples R China [23]Zhengzhou Cent Hosp, Dept Gastroenterol, Zhengzhou, Henan, Peoples R China [24]Suining Cent Hosp, Digest Dis Ctr, Dept 4, Suining, Sichuan, Peoples R China [25]Peoples Hosp Bozhou, Dept Infect Dis, Bozhou, Anhui, Peoples R China [26]Jinhua Peoples Hosp, Jinhua, Zhejiang, Peoples R China [27]Zhongshan Second Peoples Hosp, Dept Hepatol, Zhongshan, Guangdong, Peoples R China [28]Chinese Peoples Liberat Army Gen Hosp, Sr Dept Hepatol, Med Ctr 5, Beijing 100039, Peoples R China [29]Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Infect Dis, Sch Med, Shanghai, Peoples R China [30]Zhengzhou Univ, Dept Infect Dis & Hepatol, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China [31]Nanjing Univ, Nanjing Drum Tower Hosp, Affiliated Hosp, Dept Infect Dis,Med Sch, Nanjing, Jiangsu, Peoples R China [32]Shulan Hangzhou Hosp, Hangzhou, Zhejiang, Peoples R China [33]First Peoples Hosp Lianyungang, Lianyungang, Jiangsu, Peoples R China [34]Huzhou Univ, Huzhou Cent Hosp, Affiliated Cent Hosp, Huzhou 313000, Zhejiang, Peoples R China [35]Sun Yat sen Univ, Affiliated Hosp 5, Dept Infect Dis, Zhuhai, Guangdong, Peoples R China [36]Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Gen Surg, Hangzhou, Zhejiang, Peoples R China [37]Hebei Med Univ, Dept Tradit & Western Med Hepatol, Hosp 3, Shijiazhuang, Hebei, Peoples R China
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关键词: Hepatobiliary disease Hepatology Gastroduodenal disease

摘要:
Introduction Patients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus. CSPH is defined by hepatic venous pressure gradient (HVPG)>= 10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)>= 25 kPa can be used as a surrogate of HVPG >= 10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS >= 25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%-6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS >= 25 kPa may benefit from carvedilol therapy.Methods and analysis This study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS >= 25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable.Ethics and dissemination The study protocol has been approved by the ethics committees of the Sixth People's Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences.Trial registration number ChiCTR2300073864.

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出版当年[2023]版:
大类 | 3 区 医学
小类 | 3 区 医学:内科
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 医学:内科
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出版当年[2023]版:
Q1 MEDICINE, GENERAL & INTERNAL
最新[2023]版:
Q1 MEDICINE, GENERAL & INTERNAL

影响因子: 最新[2023版] 最新五年平均 出版当年[2023版] 出版当年五年平均 出版前一年[2023版]

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第一作者机构: [1]Southeast Univ, Med Sch, Zhongda Hosp, Ctr Portal Hypertens,Dept Radiol,Nurturing Ctr Jia, Nanjing, Jiangsu, Peoples R China [2]Southeast Univ, Zhongda Hosp, Basic Med Res & Innovat Ctr, Minist Educ,State Key Lab Digital Med Engn, Nanjing, Peoples R China
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通讯机构: [1]Southeast Univ, Med Sch, Zhongda Hosp, Ctr Portal Hypertens,Dept Radiol,Nurturing Ctr Jia, Nanjing, Jiangsu, Peoples R China [2]Southeast Univ, Zhongda Hosp, Basic Med Res & Innovat Ctr, Minist Educ,State Key Lab Digital Med Engn, Nanjing, Peoples R China
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