P-5 阿帕奇研究设计,旨在评估用 5%人血清白蛋白进行血浆置换对住院死亡风险较高的急慢性肝衰竭患者短期存活率的有效性和安全性。

IF 3.7 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Annals of hepatology Pub Date : 2024-02-01 DOI:10.1016/j.aohep.2023.101192
Nikolaos Pyrsopoulos , Giovanni Perricone , Jasmohan S. Bajaj , Thierry Gustot , Thomas Reiberger , Mireia Torres , Peter Nelson , Javier Fernandez , Apache Study Investigators
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引用次数: 0

摘要

导言和目的肝硬化患者急性慢性肝功能衰竭(ACLF)的特点是肝功能急性恶化和严重的器官损伤,短期死亡率高。肝移植是提高存活率的唯一治疗方法。一项试点研究表明,用人血清白蛋白 5%(PEA5%)作为替代液进行血浆置换对 ACLF 患者是可行且安全的,并可改善器官功能和存活率。本研究旨在通过一项关键性研究评估 PE-A5% 作为 ACLF 患者的治疗方法。材料与方法一项第 3 期、多中心、随机(1:1)、对照、平行组、开放标签研究(APACHE)将标准药物治疗(SMT)+ PE-A5%(治疗组)与单纯 SMT(对照组)进行了比较。PE-A5% 采用 Albutein 5% (Grifols)。治疗计划包括连续两天的首次 PE-A5% 治疗,然后隔天进行一次 PE-A5%(最少-最多 4-9 次 PE-A5%)。患者在每两次 PE-A5% 后接受 IVIG(200 毫克/千克),以预防与低丙种球蛋白血症相关的感染,并在每次 PE-A5% 后接受 FFP,以预防凝血病。符合条件的患者为成人(18-79 岁),入院时或住院期间患有 ACLF-1b、ACLF-2 或 ACLF-3a。主要排除标准为:ACLF-1a或ACLF-3b患者、随机化前10天患有ACLF的患者、需要去甲肾上腺素(0.3µg/kg/min)或第二种血管抑制剂的脓毒性休克患者、活动性感染患者以及严重呼吸衰竭患者。主要疗效终点是 90 天总生存率。次要疗效终点包括 90 天无移植生存率和 28 天总生存率。主要探索性终点包括第28天和第90天的总生存率和无移植生存率、住院时间和重症监护室停留时间、器官功能衰竭发生率以及 ACLF 病程。安全性分析包括不良事件、生命体征、身体评估和实验室检查。结论APACHE将提供有关PE-A5%作为改善ACLF存活率的治疗方法的有效性和安全性的关键性结果(NCT03702920;EudraCT:2016-001787-10)。
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P-5 APACHE STUDY DESIGN TO EVALUATE THE EFFICACY AND SAFETY OF PLASMA EXCHANGE WITH HUMAN SERUM ALBUMIN 5% ON SHORT-TERM SURVIVAL IN PATIENTS WITH ACUTE-ON-CHRONIC LIVER FAILURE AT HIGH RISK OF HOSPITAL MORTALITY.

Introduction and Objectives

Acute-on-chronic liver failure (ACLF) in cirrhotic patients is characterized by acute deterioration of liver function and severe organ injury with high short-term mortality. Liver transplantation is the only treatment to improve survival. A pilot study suggested that plasma exchange with human serum albumin 5% (PEA5%) as a replacement fluid is feasible and safe in ACLF patients and may improve organ function and survival. This study aimed to assess PE-A5% as a treatment for patients with ACLF in a pivotal study.

Materials and Methods

A phase 3, multicenter, randomized (1:1), controlled, parallel-group, open-label study (APACHE) compares standard medical treatment (SMT) + PE-A5% (treatment arm) to SMT alone (control arm). PE-A5% is performed using Albutein 5% (Grifols). Treatment schedule consists of two initial PE-A5% sessions on consecutive days followed by every other day PE-A5% (min-max 4-9 PE-A5%). Patients receive IVIG (200mg/kg) after every 2 PE-A5% to prevent hypogammaglobulinemia-associated infections, and FFP after each PE-A5% to prevent coagulopathy. Eligible patients are adult (18-79 years old), with ACLF-1b, ACLF-2, or ACLF-3a at admission or during hospitalization. Main exclusion criteria are patients with ACLF-1a or ACLF-3b, ACLF >10 days before randomization, septic shock requiring norepinephrine (>0.3µg/kg/min) or a second vasopressor, active infection, and severe respiratory failure.

Results

Target enrollment is 380 ACLF patients at high risk of hospital mortality. The primary efficacy endpoint is the 90-day overall survival. Secondary efficacy endpoints include 90-day transplant-free survival and 28-day overall survival. Main exploratory endpoints include overall and transplant-free survival at days 28 and 90, in-patient hospital and ICU stay, incidence of organ failures and ACLF course. Safety analyses include adverse events, vital signs, physical assessments, and laboratory tests.

Conclusions

APACHE will provide pivotal results on the efficacy and safety of PE-A5% as a treatment to improve survival in ACLF (NCT03702920;EudraCT:2016-001787-10).

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来源期刊
Annals of hepatology
Annals of hepatology 医学-胃肠肝病学
CiteScore
7.90
自引率
2.60%
发文量
183
审稿时长
4-8 weeks
期刊介绍: Annals of Hepatology publishes original research on the biology and diseases of the liver in both humans and experimental models. Contributions may be submitted as regular articles. The journal also publishes concise reviews of both basic and clinical topics.
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Editorial board Global multi-societies endorsement of the MAFLD definition An Acknowledgement Biological aging accelerates hepatic fibrosis: Insights from the NHANES 2017-2020 and genome-wide association study analysis. Development of a biodegradable prosthesis through tissue engineering, for the organ-replacement or substitution of the extrahepatic bile duct
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