A Prospective, Single-Center, Non-Randomized, Clinical Trial of Transplantation of Discarded Livers Using Normothermic Machine Perfusion (NMP)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of Patients With no Graft Failure at 6 Months
研究概览
简要总结
This is a prospective, non-randomized, clinical trial of discarded liver transplants that have received normothermic machine perfusion (NMP), compared with standard cold preservation liver transplants. The discarded livers rejected by all other centers and meeting pre-NMP eligibility criteria will receive NMP using the OrganOx® metra device. The NMP-treated liver that meets the viability criteria will be transplanted to patients who are eligible and consented to the study. Liver transplant outcomes will be ascertained during 12 months post-transplantation. The results of the trial will be compared with those of contemporary comparison groups of patients who received the standard criteria donor liver transplantation.
详细描述
This is a single center, prospective, non-randomized, clinical trial to assess the feasibility of successful transplantation of NMP-treated livers to patients. First, up to 71 marginal livers declined for transplantation will be treated with NMP using the OrganOx® metra device and tested for viability using previously defined criteria. NMP-treated viable livers will be subsequently transplanted to patients (n=5 in the 1st stage; additional 10 transplantation in the 2nd stage; additional 10 transplantation in the 3rd stage: total N=25). Patients will be closely followed for clinical outcomes of the transplantation during 6 months post-transplantation. The follow-up will also be extended up to 1 year post-transplantation. The trial will compare the results to those of three comparison groups - 1) matched patients who received liver transplantation at Washington University/Barnes Jewish Hospital; 2) matched patients who received DBD liver transplantation in the OPTN/UNOS database; and 3) matched patients who received DCD liver transplantation in the OPTN/UNOS database. Given that patient safety is the priority, the trial uses a multi-stage design in which the study stops earlier when NMP-treated liver transplantation is observed to be ineffective (see trial schema in Section 3.1).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •PRE-NMP DECLINED LIVER ELIGIBILITY:
- •Inclusion Criteria:
- •DCD donor aged 6 years or greater and liver weight between 1 kg and 3.4 kg, with functional warm ischemic time (defined as the period between the systolic blood pressure less than 60 mmHg to the time of commencing donor aortic perfusion) in DCD donors less than 40 minutes
- •DCD asystolic warm ischemia time (from heartbeat stopping to initiation of cold flush) less than 15 minutes
- •DBD donor aged 6 years or greater and liver weight between 1 kg and 3.4 kg, with less than 8 hours cold ischemia time and DCD livers with less than 7 hours cold ischemia time (defined as the interim from initiation of donor in vivo cold organ preservation to removal of the liver graft from cold storage)
- •'Rapid Recovery' donors for liver procurement, meeting the above criteria
- •Suboptimal in situ flush
排除标准
- •DBD or DCD donor less than 6 years old
- •DCD grafts with donor functional warm ischemic time (defined as the period between the systolic blood pressure less than 60 mmHg to the time of commencing donor aortic perfusion) greater than or equal to 40 minutes
- •DCD asystolic warm ischemia time (from heartbeat stopping to initiation of cold flush) greater than or equal to 15 minutes
- •DBD livers with cold ischemia time greater than or equal to 8 hours and DCD livers with greater than or equal to 7 hours cold ischemia time
- •Donor serum bilirubin greater than or equal to 5 mg/dL
- •Liver weight less than 1 kg or greater than or equal to 3.5 kg
- •Grafts from patients with HIV infection
- •Cirrhotic livers
- •Livers with bridging fibrosis
- •LIVER TRANSPLANTATION - HUMAN
- •Inclusion criteria:
- •Subject must be greater than or equal to 18 years of age.
- •Subject with end-stage liver disease who is actively listed for primary liver transplantation on the UNOS waiting list
- •Subject, or a legally authorized representative, has given informed consent to participate in the study
- •Subject has a frailty classification of "Mild frailty/No frailty (Robust)", based on the Liver Frailty Index (LFI), which has been assessed within 6 months prior to liver transplant OR Subject is able to perform >350 m on a 6 minute walk test (6MWT) within 6 months prior to liver transplant.
- •In all cases, the "most recent" (and within 6 months prior to transplant) measurement of LFI or 6MWT will be used to determine eligibility.
- •Exclusion criteria:
- •Subject is currently listed as a UNOS status 1A.
- •Subject is requiring oxygen therapy via ventilator/respiratory support.
- •Subject is planned to undergo simultaneous solid organ transplant.
- •Subject is pregnant at the time of transplant.
- •Subject MELD score 29 or higher
- •Subject receives re-transplantation of liver.
研究组 & 干预措施
Declined liver in Normothermic Machine Perfusion (NMP)
The discarded livers rejected by all other centers and meeting pre-NMP eligibility criteria will receive NMP using the OrganOx® metra device. The NMP-treated liver that meets the viability criteria will be transplanted to patients who are eligible and consented to the study. NMP of the donated declined liver utilizing the OrganOx® metra device. NMP involves (warm) machine perfusion with oxygenated blood at normal body temperature. During NMP, the device also allows for ongoing assessment of donor liver function and further viability assessment to help determine suitability of the organ for transplant.
干预措施: Declined liver in Normothermic Machine Perfusion (NMP) (Device)
Standard cold preservation of liver
This group will receive liver transplant using the standard method of preservation. There will be 3 comparison groups: one local comparison group and two comparison groups from the national UNOS data.
干预措施: Standard cold preservation of liver (Procedure)
结局指标
主要结局
Number of Patients With no Graft Failure at 6 Months
时间窗: Up to 6 months
6-month graft survival as an indicator of liver function after NMP- treated liver transplantation. This is a nationally accepted outcome routinely assessed in organ transplantation programs. 6-month graft survival rate = (Number of patients with no graft failure at 6-month post transplantation)/(Total number patients who received transplantation with NMP-treated liver)
6-month Patient Survival
时间窗: Up to 6 months
6-month patient survival rate = (Number of patients who survive by 6-month post transplantation)/(Total number patients in the cohort who received transplantation)
次要结局
- Liver Graft Function Assessment: Early Allograft Dysfunction(First 7 days)
- Liver Graft Function Assessment: Primary Non-Function (PNF)(First 7 days)
- No Graft Failure at 90 Days(3 months)
- 90-day Patient Survival(3 months)
- Number of Patients With no Graft Failure at 12 Months(12 months)
- 12-Month Patient Survival(12 months)
- Incidence of Intrahepatic Biliary Strictures(12 Months)
- Incidence of Vascular Complications(0-12 months)
- Event Rate of Requirement of Renal Replacement Therapy(0-12 Months)
- Incidence of Biopsy-Proven Acute Rejection(0-12 months)
- Event Rate of Transplant Related Reoperation Rate(0-12 Months)
- Length of ICU Stay(0-3 Months)
- Length of Hospital Stay(0-2 Months)
- Event Rate of Readmissions(0-12 Months)
- Quality of Life Score(0-6 Months)
- NMP-treated Liver Rescue Rate(course of study)