Multicenter, Prospective, Open-label, Randomized Controlled Clinical Trial to Compare the Safety & Effectiveness of the VitaSmart Liver Machine Perfusion System With Static Cold Storage for Organ Preservation Prior to Liver Transplantation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 228
- 试验地点
- 21
- 主要终点
- Proportion of patients with early allograft dysfunction (EAD)
研究概览
简要总结
This is a prospective, multi-center, controlled, randomized, pivotal study to evaluate the safety and effectiveness of the VitaSmart™ Liver Machine Perfusion System by comparing clinical outcomes in patients undergoing liver transplantation with ex-vivo liver preservation using static cold storage (SCS) followed by hypothermic oxygenated machine perfusion (HOPE) versus SCS only.
详细描述
Patients on the UNOS waiting list for liver transplantation who have been consented, meet study eligibility criteria and are matched to a liver allograft from donation after brain death (DBD) or donation after circulatory death (DCD) that meet the extended risk eligibility criteria will be randomized 1:1 to SCS followed by HOPE (HOPE arm) or to SCS only (SCS arm). The objective of the study is to demonstrate the safety and effectiveness of the VitaSmart™ Liver Machine by comparing endpoints between the HOPE and SCS arms.
Following transplantation, patients will be monitored daily (labs, adverse events, medications/procedures) while inpatient, and then additionally on Days 14 and 30 and Months 3, 6 and 12. The primary efficacy endpoint of early allograft dysfunction (EAD) rate will be assessed between HOPE and control using a non-inferiority design. An interim analysis is planned after approximately 70% of patients have been completed primary endpoint data collection to assess for early study completion based on non-inferiority or superiority.
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
- Single (Outcomes Assessor)
盲法说明
A centralized radiologist who evaluates imaging (MRCP and ERCP) for one of the secondary endpoints (ischemic cholangiopathy) will be blinded to treatment assignment. The study is otherwise open label.
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
- •Donation after Brain Death (DBD) Liver Inclusion Criteria (one or more):
- •Donor age 50-85 years
- •Anticipated cold ischemia time 10-15 hours (excluding HOPE duration)
- •Macrosteatosis 10-40%
- •Terminal ALT 250-1500 IU/ml
- •Peak ALT within 3 days 1000-3000 IU/ml
- •Terminal total bilirubin 2-4 mg/dl
- •Donation after Brain Death (DBD) Liver
排除标准
- •(one or more):
- •Donor age <18 or >85 years
- •Anticipated cold ischemia >15 hours
- •Macrosteatosis >40%
- •Terminal ALT >1500 IU/ml
- •Peak ALT within 3 days >3000 IU/ml
- •Terminal total bilirubin >4 mg/dl
- •Presence of hemodynamic and/or anatomical donor abnormalities that, in the opinion of the Investigator, make the liver allograft unsuitable for transplant into the recipient subject
- •Liver intended for split transplant
- •Liver from living donor
- •Donor terminal serum Na >160 mmol/L
- •Donation after Cardio-circulatory Death (DCD) Liver Inclusion Criteria (all):
- •Donor age 18-60 years
- •Anticipated cold ischemia time <12 hours (excluding HOPE duration)
- •Functional warm ischemia time ≤35 minutes, defined as interval from the time of onset of donor hypotension (MAP <50mmHg) until the time of donor cross clamp
- •Macrosteatosis ≤20%
- •Terminal ALT ≤500 IU/ml
- •Peak ALT within 3 days ≤2000 IU/ml
- •Terminal total bilirubin ≤3 mg/dl
- •Donation after Cardio-circulatory Death (DCD) Liver Exclusion Criteria (one or more):
- •Presence of hemodynamic and/or anatomical donor abnormalities that, in the opinion of the Investigator, make the liver allograft unsuitable for transplant into the recipient subject
- •Liver intended for split transplant
- •Liver from living donor
- •Donor terminal serum Na >160 mmol/L
- •Recipient Inclusion Criteria (one or more):
- •Subject (or legally authorized representative) is able to provide informed consent and HIPAA authorization
- •Subject is male or female and at least 18 years of age
- •Subject is registered as an active liver recipient on the UNOS waiting list for liver transplantation
- •Subject will undergo primary liver transplantation
- •Subject is willing to comply with the study requirements and procedures
- •Subject with hepatocellular carcinoma as indication for Orthotopic Liver Transplantation; the tumor must be within Milan Criteria or down-staged to Milan Criteria
- •Recipient Exclusion Criteria (one or more):
- •Subject will undergo multiple organ transplantations (liver-kidney, liver-lung, etc.)
- •Subject is listed for liver transplantation due to fulminant liver failure (UNOS status 1A)
- •Subject is pregnant
- •Subject is on respiratory (ventilator dependent) and/or cardiocirculatory support (requires at least one intravenous inotrope to maintain hemodynamics)
- •Subject is enrolled in an interventional clinical trial with an investigational drug or device
研究组 & 干预措施
Hypothermic oxygenated perfusion (HOPE)
Ex-vivo donor liver preservation using static cold storage followed by HOPE using the VitaSmart™ Liver Machine
干预措施: Static cold storage (Other)
Hypothermic oxygenated perfusion (HOPE)
Ex-vivo donor liver preservation using static cold storage followed by HOPE using the VitaSmart™ Liver Machine
干预措施: VitaSmart™Liver Machine Perfusion System (Device)
Static Cold Storage (SCS)
Ex-vivo donor liver preservation using static cold storage only
干预措施: Static cold storage (Other)
结局指标
主要结局
Proportion of patients with early allograft dysfunction (EAD)
时间窗: At Day 7 post-transplant
Early Allograft Dysfunction (EAD)
时间窗: 7 days
Proportion of participants with EAD by 7 days post-transplant (or at hospital discharge if prior to 7 days). Defined by the presence of one or more of the following outcomes: * Serum bilirubin ≥10 mg/dL at day 7 post-transplant * INR ≥1.6 at day 7 post-transplant * ALT or AST \>2000 IU/L within the first 7 days post-transplant
Graft Survival at 6 Months
时间窗: 6 months following transplantation
Graft survival is defined as absence of death or graft failure
Participant Survival at 6 Months
时间窗: 6 months following transplantation
Participant survival is defined as absence of death.
次要结局
- Incidence of biopsy-proven liver rejection(6 months, 1 year post-transplant)
- Proportion of patients with primary non-function (PNF)(Within 7 days post-transplant)
- Length of hospital stay(Up to study participation ends at 1-year follow-up)
- Donor liver utilization rate(Up to study participation ends at 1-year follow-up)
- Model for early allograft function (MEAF) score(Within 3 days post-transplant)
- Duration on dialysis(Up to study participation ends at 1-year follow-up)
- Patient survival rate(30 days, 6 months, 1 year post-transplant)
- Graft survival rate(30 days, 6 months, 1 year post-transplant)
- Incidence of adverse events (AEs)(1 year post-transplant)
- Incidence of unanticipated adverse device effects (UADEs)(1 year post-transplant)
- Length of intensive care unit stay(Up to study participation ends at 1-year follow-up)
- Incidence of serious AEs (SAEs)(1 year post-transplant)
- Incidence of ischemic cholangiopathy(6 months, 1 year post-transplant)
- Graft Survival at 12 Months/30 Days(Up to 12 months following transplantation)
- Participant Survival at 12 Months/30 Days(Up to 12 months following transplantation)
- Model for Early Allograft Function (MEAF) Score(Within 3 days post-transplant)
- Primary Non-function (PNF)(Within 7 days post-transplant)
- Length of Hospital Stay(End of surgery to hospital discharge)
- Length of Intensive Care Unit Stay(End of surgery to ICU discharge)
- Duration on Renal Replacement Therapy (RRT)(Post-transplantation until RRT discontinued for >2 weeks)
- Donor Liver Utilization(Randomization to transplantation)
- Biopsy-proven Liver Rejection(Up to 12 months following transplantation)
- Central Radiologist Diagnosed Non-anastomotic Strictures (NAS)(Up to 12 months after transplantation)
- Unanticipated Adverse Device Effects (UADEs)(12 months after transplantation)