End-ischemic Hypothermic Oxygenated Perfusion for Extended Criteria Donors in Liver Transplantation - A Multicenter, Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 266
- 试验地点
- 16
- 主要终点
- Early allograft dysfunction (EAD) according to Olthoff criteria.
研究概览
简要总结
Given the scarce donor supply, an increasing number of so-called marginal or extended criteria donor (ECD) organs have been used for liver transplantation. These ECD liver grafts are, however, known to be associated with a higher rate of early allograft dysfunction (EAD) and primary non-function because of a greater vulnerability to ischemia-reperfusion injury. The end-ischemic Hypothermic Oxygenated Machine Perfusion (HOPE) technique may improve outcomes of liver transplantation with ECD grafts by decreasing reperfusion injury.
The study aim is to assess the efficacy of HOPE used before transplantation of ECD liver grafts from brain-dead donors in reducing postoperative EAD within the first 7 postoperative days (POD) compared to simple cold static storage.
The study is comparative open-label, multicenter, national, prospective, randomized, in two parallel groups, using the gold standard procedure as control.
详细描述
This multicentric randomized controlled trial concerns adult patients undergoing whole liver transplantation in any of the 8 participating centers in France, who will receive an ECD liver graft from a brain-dead donor.
After providing written informed consent prior to the performance of any study specific procedure, the recruited patients will be randomized either in the experimental group (HOPE group) or in the control group.
In the HOPE group, ECD liver grafts will undergo a hypothermic oxygenated perfusion (HOPE) via the portal vein for a period of 1 to 4 hours (minimum 1 hour) after the "back-table" phase (graft preparation), in parallel with the recipient hepatectomy, using the CE-certified Liver Assist® perfusion pump/device (Organ Assist®, the Netherlands) with Machine Perfusion Solution (Belzer-MPS, CE-certified).
The control group will consist of a classic static cold (4°C) storage with Institute George Lopez (IGL-1)® solution from graft harvesting until liver transplantation, which is the gold standard procedure in liver transplantation.
The primary endpoint will be early allograft dysfunction (EAD) according to Olthoff's criteria, which will be compared with the Model of Early Allograft Function score (MEAF score) and the Liver Graft Assessment Following Transplantation risk factor (L-GrAFT).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provide written informed consent prior to the performance of any study specific procedure
- •Affiliated to the French social security system
- •Recipient age ≥ 18 years
- •Patients undergoing primary liver transplantation.
- •Candidate for a first elective liver transplantation, whatever the indication, with a liver graft harvested from a brain-dead ECD defined by the presence of at least one of the following criteria:
- •Donor age > 65 years
- •Intensive care unit stay > 7 days
- •BMI > 30
- •Proven macro-steatosis biopsy ≥ 30%
- •Natremia > 155 mmol/L at any time
- •AST > 150 IU/mL at any time
- •ALT > 170 IU/mL at any time.
排除标准
- •Fulminant hepatic failure
- •Retransplantation
- •Split liver transplantation
- •Living donor liver transplantation
- •Grafts donated after cardiac arrest (DCD grafts)
- •Domino transplantation
- •Combined liver transplant
- •Unexpected medical contraindication to liver transplantation
- •Patient participating in other interventional research, excluding routine care research (old regulation) and category 2 research not interfering with primary endpoint analysis
- •Patient under legal protection
- •Patient deprived of liberty by a judicial or administrative decision
- •Patient refusing to participate in the study
- •Pregnant or lactating women
- •Inability to understand information concerning the protocol
结局指标
主要结局
Early allograft dysfunction (EAD) according to Olthoff criteria.
时间窗: During the first postoperative week
EAD is defined by the presence of at least one of the following criteria: * Bilirubin level \> 10 mg/dL (i.e. 171 µmol/L) on POD 7 * International Normalized Ratio (INR) \> 1.6 on POD 7 * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels \> 2000 IU/L within the first 7 PODs Additionally EAD will be also assessed by the MEAF score and the L-GrAFT risk factor.
次要结局
- Model of Early Allograft Function score (MEAF score).(During the first 3 postoperative days.)
- Occurrence of post-reperfusion syndrome(Day of liver transplantation (Day 0))
- 3-month and one-year patient and graft survivals(within one year after liver transplantation)
- Untargeted liver graft metabolic profiling(Day of liver transplantation (Day 0))
- Liver Graft Assessment Following Transplantation risk factor (L-GrAFT)(During the first 10 postoperative days.)
- Liver contrast-enhanced MRI including a Magnetic Resonance CholangioPancreatography (MRCP)(Within 1 year after liver transplantation)
- 90-day morbidity and mortality(During the first 90 days after surgery.)
- Hospital costs (Euros) of liver transplantation(At one year after liver transplantation)
- Length of intermediate care unit stay (days)(From randomization until intermediate care unit discharge, estimated up to 7 days)
- Length of hospital stay (days)(From randomization until hospital discharge, estimated up to 21 days)