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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
A single dose strength of treprostinil sodium (1.0 mg/mL) and matching placebo will be provided in 20-mL multi-dose vials. The study drug will be started after induction of anesthesia and increased incrementally to a target dose of 10 ng/kg/min during surgery and 48 hours post-operative
University of Pittsburgh Medical Center, Starzl Transplantation Institute
Pittsburgh, Pennsylvania, United States
Duration of the initial hospitalization (days) following transplantation
Time frame: up to 180 days
Area under the curve (AUC) of serum aspartate transaminase (AST) levels.
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.
Time frame: 7 days
Serum AST and alanine transaminase (ALT ) levels after transplant (Peak and Area Under the Curve [AUC])
Time frame: 7 days
Primary allograft nonfunction defined as patient death or retransplant within 30 days due to liver failure
Time frame: 30 days
Graft survival
Time frame: 30 days, 90 days and 180 days
Subject survival at
Time frame: Day 30, 90, and 180
Post-transplant renal function
Time frame: 30 days
Duration of time spent in the intensive care unit (ICU; days) during the initial hospitalization.
Time frame: up to 180 days
Intra-operative blood product usage
Time frame: 1 day
Death from any cause
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Time frame: 180 days
Total costs for initial transplant hospitalization
Time frame: up to 180 days