Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial
Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial
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DOI：
10.1016/s0140-6736(18)30840-7
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发表时间：
2018-06-16
期刊：
影响因子：
168.9
通讯作者：
Bernardi, Mauro
中科院分区：
文献类型：
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作者：
Caraceni, Paolo;Riggio, Oliviero;Bernardi, Mauro
背景失代偿期肝硬化患者长期使用人血白蛋白（HA）的疗效证据很少。人血白蛋白的治疗meNt的aScites患者hEscherichiRhosis（ANSWER）研究的目的是澄清这一问题，方法我们做了一个制药商发起的多中心随机，平行，开放标签，务实的试验在33个学术和非学术意大利医院。我们将接受抗醛固酮药物（>= 200 mg/天）和呋塞米（>= 25 mg/天）治疗的肝硬化和无并发症腹水患者随机分配至接受标准药物治疗（SMT）或SMT加HA（40 g每周两次，持续2周，然后每周40 g），持续18个月。主要终点为18个月死亡率，评价为改良意向治疗人群和符合方案人群中患者的事件差异和生存时间分析。本研究已在EudraCT（编号2008-000625-19）和ClinicalTrials注册。结果从2011年4月2日至2015年5月27日，440名患者被随机分配，431名患者被纳入改良的意向治疗分析。SMT + HA组218例患者中38例死亡，SMT组213例患者中46例死亡。SMT + HA组的总体18个月生存率显著高于SMT组（Kaplan-Meier估计值为77% vs 66%; p=0.028），导致死亡风险比降低38%（0.62 [95%CI 0.40-0.95]）。SMT组中46名（22%）患者和SMT加HA组中49名（22%）患者具有3-4级非肝脏相关的不良事件。(C)2018爱思唯尔有限公司版权所有。
Background Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue.Methods We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (>= 200 mg/day) and furosemide (>= 25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008-000625-19, and ClinicalTrials. gov, number NCT01288794.Findings From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0.028), resulting in a 38% reduction in the mortality hazard ratio (0.62 [95% CI 0.40-0.95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3-4 non-liver related adverse events.Interpretation In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. (C) 2018 Elsevier Ltd. All rights reserved.