A Phase I Pilot Study to Assess Safety and Feasibility of Normothermic Machine Preservation In Human Liver Transplantation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- the rate of Early Allograft Dysfunction post-transplantation in Normothermically Machine Perfused (NMP) livers
研究概览
简要总结
Normothermic machine perfusion (NMP) preservation is a promising method to decrease the complication of marginal donor livers compared to cold storage (CS). The aim of this project is to assess safety and feasibility of NMP in human liver transplantation. This will be a single center prospective cohort pilot study. Thirty-two livers with acceptable quality for transplantation will be preserved with NMP in 2-18 hours and transplanted. The follow-up period will be 6 months post-transplantation. The outcome will be compared to 100 historical patients transplanted in our program in the past 5 years (liver preserved using CS) with matched characteristics on age, Model for End-Stage Liver Disease (MELD) score, preservation time, etc.
详细描述
The shortage of donor organs leads to the use of marginal donors including donors after cardiac death. Normothermic machine perfusion (NMP) preservation is a promising method to decrease their high risk of complication compared to the standard cold storage (CS). The aim of this project is to assess safety and feasibility of NMP in human liver transplantation.
This will be a single center prospective cohort pilot study. Thirty-two livers that have acceptable quality for transplantation will be preserved with NMP in 2-18 hours after cross clamp and cold flush. The liver grafts at NMP will be at physiological temperature and have oxygen and nutrient supply with continuous perfusion. The transplantation and post-transplant care will follow the standard of care. The follow-up period is 12 months after transplantation. The primary end point will be the rate of post-transplant Early Allograft Dysfunction (EAD), while the secondary end points will be: primary non function (PNF) rate, 1 and 6 months patient and graft survival, peak liver function tests in the first 7 days after transplantation, intraoperative hepatic arterial and portal flow measurement, rate and magnitude of post-reperfusion syndrome, surgical outcomes (operative time, transfusion requirement etc.), rate of post-transplant kidney failure, assessment of histological ischemia reperfusion (liver and bile duct), rate of vascular complications, rate of biliary complications, hospital and ICU length of stay, rejection rate, infection rate, the ability to predict function based on "on-pump" viability markers, and the incidence of adverse effect (AE).
The outcome will be compared to a control group of 100 historical patients (matched with a 1:4 ratio) transplanted in our program in the past 10 years (liver preserved using CS). Control subjects will be matched using donor and recipient age, Model for End-Stage Liver Disease (MELD) score, cold ischemia time, donor risk index and presence of steatosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients undergoing primary liver transplantation
- •Age 18-75 years at the time of transplantation
- •Willingness and ability to comply with the study procedures
- •Signed Informed Consent Form
- •For patients with hepatocellular carcinoma as indication for Orthoptic Liver Transplantation (OLT), tumor must be within Milan Criteria or down-staged to Milan Criteria.
排除标准
- •Recipient Exclusion Criteria:
- •History of prior solid organ transplantation
- •Patient on a respiratory and/or cardiocirculatory support at the time of transplant
- •MELD score >35
- •HIV positive patient
- •Patient with current severe systemic infection
- •Multiorgan transplant
- •Donor Exclusion Criteria:
- •Donor age <14 or >70 years
- •Liver steatosis (on visual estimate or on liver biopsy) > 30%
- •Donors with Grade 2-3 traumatic liver laceration
- •Partial grafts (living donors and split liver donors)
- •Liver in which the investigator is unwilling or unable (for logistical reasons) to perform normothermic machine perfusion (NMP) preservation
- •Inability to NMP perfuse the liver within 4 hours after cross clamp
结局指标
主要结局
the rate of Early Allograft Dysfunction post-transplantation in Normothermically Machine Perfused (NMP) livers
时间窗: 7 days post-transplantation
The presence of at least one of the following at post-transplant 7 days: serum bilirubin \>= 10 mg/dL, international normalized ratio (INF) \>= 1.6; and/or aspartate aminotransferase (AST) \> 2000 U/L at any time in the first 7 post-transplant days (POD)
次要结局
- surgical outcomes (composite)(intraoperative)
- primary non-function rate(in the first 10 days post-transplantation)
- graft survival(6 months post-transplantation)
- peak liver function tests in the first 7 days post-transplantation(in the first 7 days post-transplantation)
- intraoperative flow measurement(intraoperative)
- post reperfusion syndrome (composite)(in the first 7 days post-transplantation)
- rate of post-transplant kidney failure(in the 1, 3, 6 ,9 months post-transplantation)
- histology of liver parenchyma(On the day of transplantation)
- vascular complications rate(in the first day post-transplantation)
- biliary complications rate(6 months post-transplantation)
- hospital and ICU length of stay (composite)(6 months post-transplantation)
- rejection rate(6 months post-transplantation)
- opportunistic viral infection rate(6 months post-transplantation)
- patient survival(6 months post-transplantation)
- histology of bile duct(On the day of transplantation)
研究者
Cristiano Quintini
Sponsor-Investigator
The Cleveland Clinic