Tripathi Dhiraj, Handley Kelly, Holden Lisa, Abdali Zainab, Jowett Sue, Mathers Jonathan, Poyner Christopher, Richardson Paul, Ferguson James, Rowe Ian
Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham Health Partners, Birmingham, UK.
Immunology and Immunotherapy, College of Medicine and Health, University of Birmingham, Birmingham Health Partners, Birmingham, UK.
Aliment Pharmacol Ther. 2025 Jun;61(11):1740-1754. doi: 10.1111/apt.70080. Epub 2025 Apr 16.
The superior efficacy of non-selective beta-blockers (NSBB) compared with variceal band ligation (VBL) in the primary prevention of variceal bleeding is uncertain.
To compare carvedilol versus VBL for primary prevention of variceal bleeding.
CALIBRE was an investigator-initiated, multicentre, randomised, controlled, open-label trial. Participants were randomly assigned to 12.5 mg carvedilol once daily or VBL. Inclusion criteria were cirrhosis and medium to large oesophageal varices that had not bled. The primary outcome is any variceal bleeding within 1 year of randomisation. Secondary outcomes include survival, other complications of cirrhosis, quality of life, cost-effectiveness and adverse events. Recruitment closed early, mainly due to the impact of the pandemic.
265 participants (10% of the intended sample size) from 52 sites were randomised to carvedilol (n = 133) or VBL (n = 132) between 22 January 2019 and 31 August 2022. 5/133 participants (3.8%) in the carvedilol arm vs. 10/132 participants (7.6%) in the VBL arm experienced variceal bleeding (risk ratio 0.50 (95% confidence interval [CI]; 0.17-1.41); risk difference - 0.038 (95% CI; -0.094-0.017)). Serious adverse events occurred in one participant in each treatment arm, with no treatment-related deaths. Of the secondary outcomes, there were no statistically significant differences. Carvedilol was cheaper and resulted in slightly more quality-adjusted life years than VBL.
The early terminated and, thus, underpowered CALIBRE trial showed no difference between carvedilol and VBL in the primary prevention of variceal bleeding in patients with cirrhosis and medium-to large-sized oesophageal varices. No untoward safety concerns were noted.
ISRCTN73887615.
在预防静脉曲张出血的一级预防中，非选择性β受体阻滞剂（NSBB）与静脉曲张套扎术（VBL）相比，其卓越疗效尚不确定。
比较卡维地洛与VBL在预防静脉曲张出血一级预防中的效果。
CALIBRE是一项由研究者发起的、多中心、随机、对照、开放标签试验。参与者被随机分配至每日一次服用12.5毫克卡维地洛或接受VBL。纳入标准为肝硬化且有未出血的中至大食管静脉曲张。主要结局是随机分组后1年内发生的任何静脉曲张出血。次要结局包括生存率、肝硬化的其他并发症、生活质量、成本效益和不良事件。招募提前结束，主要是由于疫情的影响。
2019年1月22日至2022年8月31日期间，来自52个地点的265名参与者（占预期样本量的10%）被随机分配至卡维地洛组（n = 133）或VBL组（n = 132）。卡维地洛组133名参与者中有5名（3.8%）发生静脉曲张出血，而VBL组132名参与者中有10名（7.6%）发生静脉曲张出血（风险比0.50（95%置信区间[CI]；0.17 - 1.41）；风险差 -0.038（95% CI；-0.094 - 0.017））。每个治疗组各有一名参与者发生严重不良事件，无治疗相关死亡。在次要结局方面，无统计学显著差异。卡维地洛更便宜，且比VBL产生的质量调整生命年略多。
提前终止且因此效力不足的CALIBRE试验表明，在肝硬化和中至大食管静脉曲张患者的静脉曲张出血一级预防中，卡维地洛与VBL之间无差异。未发现不良安全问题。
ISRCTN73887615
