Department of Medical and Surgical Sciences, and Center for Applied Biomedical Research, University of Bologna, Bologna, Italy.
Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
Lancet. 2018 Jun 16;391(10138):2417-2429. doi: 10.1016/S0140-6736(18)30840-7. Epub 2018 Jun 1.
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.
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.
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.
In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis.
Italian Medicine Agency.
长期给予人血白蛋白（human albumin，HA）治疗失代偿期肝硬化患者的疗效证据有限。本研究旨在阐明这一问题，故开展了一项由研究者发起的多中心、随机、平行、开放标签、实用临床试验。
我们在意大利 33 家学术和非学术医院开展了这项研究。我们将正在接受醛固酮拮抗剂（≥200mg/天）和呋塞米（≥25mg/天）治疗且无并发症性腹水的肝硬化患者随机分为标准治疗（SMT）组或 SMT 加 HA 组（前 2 周每周 2 次给予 40g，随后每周给予 40g），治疗时间最长为 18 个月。主要终点为 18 个月死亡率，评估方法为改良意向治疗人群和方案人群中纳入患者的事件差异和生存时间分析。本研究在 EudraCT 注册，编号为 2008-000625-19，在 ClinicalTrials.gov 注册，编号为 NCT01288794。
从 2011 年 4 月 2 日至 2015 年 5 月 27 日，共有 440 例患者被随机分配，431 例患者纳入改良意向治疗分析。SMT 加 HA 组和 SMT 组分别有 218 例患者中的 38 例和 213 例患者中的 46 例死亡。SMT 加 HA 组的 18 个月总生存率明显高于 SMT 组（Kaplan-Meier 估计值分别为 77%和 66%；p=0·028），死亡风险比降低 38%（0·62 [95%CI 0·40-0·95]）。SMT 组和 SMT 加 HA 组各有 22%（46 例）和 22%（49 例）的患者发生 3-4 级非肝脏相关不良事件。
在这项试验中，长期给予 HA 治疗可延长总体生存率，可能作为失代偿期肝硬化患者的一种疾病修正治疗。
意大利药品管理局。
