Nikolaos Pyrsopoulos , Giovanni Perricone , Jasmohan S. Bajaj , Thierry Gustot , Thomas Reiberger , Mireia Torres , Peter Nelson , Javier Fernandez , Apache Study Investigators
{"title":"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。","authors":"Nikolaos Pyrsopoulos , Giovanni Perricone , Jasmohan S. Bajaj , Thierry Gustot , Thomas Reiberger , Mireia Torres , Peter Nelson , Javier Fernandez , Apache Study Investigators","doi":"10.1016/j.aohep.2023.101192","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction and Objectives</h3><p>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.</p></div><div><h3>Materials and Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusions</h3><p>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).</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1665268123002958/pdfft?md5=8d6962308fbc79301a93d2eb15e3d679&pid=1-s2.0-S1665268123002958-main.pdf","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"Nikolaos Pyrsopoulos , Giovanni Perricone , Jasmohan S. Bajaj , Thierry Gustot , Thomas Reiberger , Mireia Torres , Peter Nelson , Javier Fernandez , Apache Study Investigators\",\"doi\":\"10.1016/j.aohep.2023.101192\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction and Objectives</h3><p>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.</p></div><div><h3>Materials and Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusions</h3><p>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).</p></div>\",\"PeriodicalId\":7979,\"journal\":{\"name\":\"Annals of hepatology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1665268123002958/pdfft?md5=8d6962308fbc79301a93d2eb15e3d679&pid=1-s2.0-S1665268123002958-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of hepatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1665268123002958\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of hepatology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1665268123002958","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
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).
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.