Administration of Albumin Solution Increases Serum Levels of Albumin in Patients With Chronic Liver Failure in a Single-Arm Feasibility Trial.
Administration of Albumin Solution Increases Serum Levels of Albumin in Patients With Chronic Liver Failure in a Single-Arm Feasibility Trial.
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DOI：
10.1016/j.cgh.2017.09.012
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
O'Brien A
中科院分区：
文献类型：
--
作者：
China L;Skene SS;Shabir Z;Maini A;Sylvestre Y;Bennett K;Bevan S;O'Beirne J;Forrest E;Portal J;Ryder S;Wright G;Gilroy DW;O'Brien A
感染对于急性失代偿和慢加急性肝衰竭（AD/ACLF）患者来说是危及生命的。 AD/ACLF 患者存在前列腺素 E2 介导的免疫抑制，可通过服用白蛋白来逆转；输注 20% 人白蛋白溶液 (HAS) 可能会改善感染的结果。我们进行了可行性研究，以确定最佳试验设计、评估安全性并验证免疫功能的实验室评估，为 3 期试验的设计提供信息。我们对 2015 年 5 月至 12 月在英国 10 家医院观察的 79 名 AD/ACLF 且白蛋白水平低于 30 g/L 的患者进行了一项前瞻性多中心、单组、开放标签试验。根据血清水平，每天给患者输注 20% HAS，持续 14 天或直至出院。记录感染率、器官功能障碍和院内死亡率。主要终点是治疗期间每日血清白蛋白水平。如果 60% 的人在记录水平的至少三分之一的时间内达到并维持血清白蛋白水平等于或高于 30 g/L，则证明成功。患者的终末期疾病评分平均模型为 20.9 ± 6.6。 79 名患者中有 68 名达到了主要终点（在至少三分之一记录的天数内白蛋白≥30 g/L）； 75% 的给药符合建议的给药方案。平均治疗持续时间为 10.3 天（施用 104 ± 678 mL）。独立数据监测委员会认为，有 8 例死亡和 13 例严重不良事件与预期相符。 13 名出现呼吸或心血管功能障碍（基于病房临床定义）作为其唯一器官功能障碍的患者中，有 12 名患者在 30 天时存活，而出现肾功能障碍的 3 名患者中只有 1 名存活。仅记录了 1 例脑功能障碍。在一项可行性试验中，我们发现服用 HAS 会增加 AD/ACLF 患者的血清白蛋白水平。该给药方案在多个地点是可接受的，并且被独立数据监测委员会认为是安全的。我们还开发了一个强大的系统来记录感染。肾功能不全患者的预后不良已得到证实。然而，患有心血管或呼吸功能障碍的患者却有良好的预后，这是违反直觉的。严重脑病的报告似乎严重不足，这表明无法足够准确地记录基于病房的这些参数评估，无法用作 3 期试验的主要结局。试验注册号：EudraCT 2014-002300-24 和 ISRCTN14174793。
Infections are life-threatening to patients with acute decompensation and acute-on-chronic liver failure (AD/ACLF). Patients with AD/ACLF have prostaglandin E2–mediated immune suppression, which can be reversed by administration of albumin; infusion of 20% human albumin solution (HAS) might improve outcomes of infections. We performed a feasibility study to determine optimal trial design, assess safety, and validate laboratory assessments of immune function to inform design of a phase 3 trial. We performed a prospective multicenter, single-arm, open-label trial of 79 patients with AD/ACLF and levels of albumin lower than 30 g/L, seen at 10 hospitals in the United Kingdom from May through December 2015. Patients were given daily infusions of 20% HAS, based on serum levels, for 14 days or until discharge from the hospital. Rates of infection, organ dysfunction, and in-hospital mortality were recorded. The primary end point was daily serum albumin level during the treatment period. Success would be demonstrated if 60% achieved and maintained serum albumin levels at or above 30 g/L on at least one third of days with recorded levels. The patients’ mean model for end-stage disease score was 20.9 ± 6.6. The primary end point (albumin ≥30 g/L on at least one third of days recorded) was achieved by 68 of the 79 patients; 75% of administrations were in accordance with suggested dosing regimen. Mean treatment duration was 10.3 days (104 ± 678 mL administered). There were 8 deaths and 13 serious adverse events, considered by the independent data-monitoring committee to be consistent with those expected. Twelve of 13 patients that developed either respiratory or cardiovascular dysfunction (based on ward-based clinical definitions) as their only organ dysfunction were alive at 30 days compared with 1 of 3 that developed renal dysfunction. Only 1 case of brain dysfunction was recorded. In a feasibility trial, we found that administration of HAS increased serum levels of albumin in patients with AD/ACLF. The dosing regimen was acceptable at multiple sites and deemed safe by an independent data-monitoring committee. We also developed a robust system to record infections. The poor prognosis for patients with renal dysfunction was confirmed. However, patients with cardiovascular or respiratory dysfunction had good outcomes, which is counterintuitive. Severe encephalopathy appeared substantially under-reported, indicating that ward-based assessment of these parameters cannot be recorded with sufficient accuracy for use as a primary outcome in phase 3 trials. Trial registration no: EudraCT 2014-002300-24 and ISRCTN14174793.
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