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Abstract：
BACKGROUND: 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: 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.
BACKGROUND: 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.
BACKGROUND: ChiCTR2300073864.
METHODS: 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.
BACKGROUND: 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.
BACKGROUND: ChiCTR2300073864.
摘要：
背景：建议使用非选择性β受体阻滞剂治疗具有临床意义的门静脉高压症（CSPH）的患者（即，卡维地洛）通过更新BavenoVII共识来预防第一次肝失代偿事件。CSPH定义为肝静脉压力梯度（HVPG）≥10mmHg;然而，HVPG测量由于其侵入性而未被广泛采用。肝硬度（LS）≥25kPa可用作HVPG≥10mmHg的替代品，以统治CSPH，在大多数患者病因中有90％的阳性预测值。一个令人信服的论据是存在使用LS≥25kPa来诊断CSPH，然后开始卡维地洛患者代偿期肝硬化，在此诊断标准下,约5%-6%的患者可能无法从卡维地洛获益,并且有降低心率和平均动脉压的风险.关于使用卡维地洛预防LS诊断的CSPH中肝脏失代偿的随机对照试验仍有待阐明。因此,我们旨在调查LS≥25kPa的代偿性肝硬化患者是否可以从卡维地洛治疗中获益.
方法：这项研究是一项随机的，双盲,安慰剂对照,多中心试验。我们将随机分配446名成人代偿性肝硬化患者，LS≥25kPa，没有任何先前的失代偿期事件，也没有高风险的胃食管静脉曲张。患者随机分为两组,A组223名受试者,B组223名受试者,A组为卡维地洛干预组,B组为安慰剂组。两组中的所有患者都将接受病因治疗，并以6个月的间隔进行随访。肝硬化相关和肝脏相关死亡失代偿性事件的3年发生率是主要结果。次要结果包括门静脉高压症的每种并发症的发展（腹水，静脉曲张出血或明显的肝性脑病），自发性细菌性腹膜炎和其他细菌感染的发展，新静脉曲张的发展，小静脉曲张生长为大静脉曲张，LS和脾僵硬的δ变化，通过Child-Pugh和终末期肝病评分模型评估肝功能障碍的变化，血小板计数的变化，肝细胞癌的发展，3年随访门静脉血栓形成和不良事件的发展。将执行预定义的中期分析以确保计算是合理的。
背景：研究方案已获得沈阳市第六人民医院伦理委员会（2023-05-003-01）和中大医院临床研究独立伦理委员会的批准，隶属于东南大学(2023ZDSYLL433-P01)。该试验的结果将提交在同行评审的期刊上发表，并将在国际会议上发表。
背景：ChiCTR2300073864。
方法：这项研究是一项随机的，双盲,安慰剂对照,多中心试验。我们将随机分配446名成人代偿性肝硬化患者，LS≥25kPa，没有任何先前的失代偿期事件，也没有高风险的胃食管静脉曲张。患者随机分为两组,A组223名受试者,B组223名受试者,A组为卡维地洛干预组,B组为安慰剂组。两组中的所有患者都将接受病因治疗，并以6个月的间隔进行随访。肝硬化相关和肝脏相关死亡失代偿性事件的3年发生率是主要结果。次要结果包括门静脉高压症的每种并发症的发展（腹水，静脉曲张出血或明显的肝性脑病），自发性细菌性腹膜炎和其他细菌感染的发展，新静脉曲张的发展，小静脉曲张生长为大静脉曲张，LS和脾僵硬的δ变化，通过Child-Pugh和终末期肝病评分模型评估肝功能障碍的变化，血小板计数的变化，肝细胞癌的发展，3年随访门静脉血栓形成和不良事件的发展。将执行预定义的中期分析以确保计算是合理的。
背景：研究方案已获得沈阳市第六人民医院伦理委员会（2023-05-003-01）和中大医院临床研究独立伦理委员会的批准，隶属于东南大学(2023ZDSYLL433-P01)。该试验的结果将提交在同行评审的期刊上发表，并将在国际会议上发表。
背景：ChiCTR2300073864。
