A Single Center, Randomized, Double-Blind, Parallel Placebo-Controlled Study of the Safety and Efficacy of Perioperative Remodulin® in Orthotopic Liver Transplant Recipients
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Duration of the initial hospitalization (days) following transplantation
研究概览
简要总结
Patients undergoing orthotopic liver transplant will experience some degree of clinical and/or biochemical hepatic dysfunction. This early injury is known as primary graft dysfunction and varies from minor abnormalities to primary nonfunction. Prostaglandin-class drugs, including prostacyclin and its analogs, could represent an important advance toward the goal of reducing transplant related morbidity, mortality and associated costs by providing these benefits.
详细描述
In vitro and in vivo research has consistently demonstrated an array of potential beneficial effects of prostanoids under both immune and non-immune circumstances relevant to liver allografts. (1-3) Recent reviews summarize the pharmacologic rationale and nonclinical and clinical experience supporting for the use of prostanoids, including prostacyclin and its analogs, in reducing early morbidity and mortality associated with liver transplantation. Prostaglandin-class drugs, including prostacyclin and its analogs, could represent an important advance toward the goal of reducing transplant related morbidity, mortality and associated costs by providing these benefits. Additionally, the reduction in serum creatinine and reduced need for post-operative dialysis observed in some studies has implications in protecting the kidneys from the nephrotoxic affects of the immunosuppressant agents, especially during the early post-operative period.
As a chemically stable analog of prostacyclin (PGI2), peri-operative intravenous administration of Remodulin is hypothesized to ameliorate or prevent reperfusion damage and thereby decrease hospitalization time and improve the clinical outcome of liver transplantation, compared to placebo control. Remodulin, as a prostanoid, is expected to facilitate restoration of the blood supply to the revascularized graft, and to provide the well-characterized protective effects of this class of compounds in liver transplant patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Accepted as a liver transplant candidate at the University of Pittsburgh Medical Center
- •Be receiving a cadaver donor liver transplant
- •Treated in accordance with the standard of care protocol(s) in effect for liver transplant recipients at the University of Pittsburgh Medical Center.
排除标准
- •Receiving a living done liver transplant
- •Receiving a donor liver with a cold ischemia time less that 6 hours
- •Receiving a donor liver with macrosteatosis greater than 30%
- •Receiving any investigation drug with the except of alemtuzamab (Camphath)
- •Failed liver transplant in previous 180 days
- •Prior organ transplant or cell infusion
- •Undergoing multi-organ transplant
- •Pregnant or nursing female
研究组 & 干预措施
Remodulin
Remodulin initiated as a continuous IV infusion at a dose of 2.5 ng/kg/min after subjects have been assessed as hemodynamically stable in the ICU. Dose may be escalated in 1.25- to 2.5-ng/kg/min increments, up to 7.5 ng/kg/min, with a target dose of 5 ng/kg/min, based on tolerability. The dose will be maintained at the maximum tolerated dose, not to exceed 7.5 ng/kg/min for 5 days after the transplantation surgery.
干预措施: treprostinil sodium (Drug)
Placebo
Matching placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Duration of the initial hospitalization (days) following transplantation
时间窗: up to 180 days
Area under the curve (AUC) of serum aspartate transaminase (AST) levels.
时间窗: 7 days
The difference in serum AST as measured by AUC during the first seven days post-transplant will be compared between placebo and Remodulin treatment groups. AST is a serum transaminase marker of hepatic injury, and the AUC of AST levels represents the total magnitude of injury the liver experiences against time.
次要结局
- Primary allograft nonfunction defined as patient death or retransplant within 30 days due to liver failure(30 days)
- Total costs for initial transplant hospitalization(up to 180 days)
- Subject survival at(Day 30, 90, and 180)
- Post-transplant renal function(30 days)
- Intra-operative blood product usage(1 day)
- Death from any cause(180 days)
- Serum AST and alanine transaminase (ALT ) levels after transplant (Peak and Area Under the Curve [AUC])(7 days)
- Graft survival(30 days, 90 days and 180 days)
- Duration of time spent in the intensive care unit (ICU; days) during the initial hospitalization.(up to 180 days)