Clinical trial NCT01884038: Safety and Efficacy of Perioperative Remodulin® in Orthotopic Liver Transplant Recipients
Official title: A Single Center, Randomized, Double-Blind, Parallel Placebo-Controlled Study of the Safety and Efficacy of Perioperative Remodulin® in Orthotopic Liver Transplant Recipients
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: Liver Transplant
Keywords: Liver Transplant
Prostacyclin
Treprostinil sodium
Remodulin
Reperfusion Injury
Primary Nonfunction
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: University of Pittsburgh Medical Center
First posted: 2013-06-21
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Duration of the initial hospitalization (days) following transplantation
timeFrame: up to 180 days
measure: Area under the curve (AUC) of serum aspartate transaminase (AST) levels.
timeFrame: 7 days
Secondary outcomes:
measure: Serum AST and alanine transaminase (ALT ) levels after transplant (Peak and Area Under the Curve [AUC])
timeFrame: 7 days
measure: Primary allograft nonfunction defined as patient death or retransplant within 30 days due to liver failure
timeFrame: 30 days
measure: Graft survival
timeFrame: 30 days, 90 days and 180 days
measure: Subject survival at
timeFrame: Day 30, 90, and 180
measure: Post-transplant renal function
timeFrame: 30 days
measure: Duration of time spent in the intensive care unit (ICU; days) during the initial hospitalization.
timeFrame: up to 180 days
measure: Intra-operative blood product usage
timeFrame: 1 day
measure: Death from any cause
timeFrame: 180 days
measure: Total costs for initial transplant hospitalization
timeFrame: up to 180 days
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center, Starzl Transplantation Institute
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh Medical Center
name: Amadeo Marcos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh Medcial Center
name: Raman Venkataramanan, Ph.D, F.C.P.
role: PRINCIPAL_INVESTIGATOR
References: