Safety and Efficacy of Perioperative Remodulin® in Orthotopic Liver Transplant Recipients

Liver Transplant Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01884038
• Other study ID #: RIV-LT-301
• Status: Withdrawn
• Phase: Phase 2/Phase 3
• Start date: June 2008
• Est. completion date: June 2010

Study information

• Verified date: June 2013
• Source: United Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Liver Transplant

Intervention

Drug:
• treprostinil sodium
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
• Placebo

Locations

Country	Name	City	State
United States	University of Pittsburgh Medical Center, Starzl Transplantation Institute	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
United Therapeutics	University of Pittsburgh Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of the initial hospitalization (days) following transplantation		up to 180 days
Primary	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.	7 days
Secondary	Serum AST and alanine transaminase (ALT ) levels after transplant (Peak and Area Under the Curve [AUC])		7 days
Secondary	Primary allograft nonfunction defined as patient death or retransplant within 30 days due to liver failure		30 days
Secondary	Graft survival		30 days, 90 days and 180 days
Secondary	Subject survival at		Day 30, 90, and 180
Secondary	Post-transplant renal function		30 days
Secondary	Duration of time spent in the intensive care unit (ICU; days) during the initial hospitalization.		up to 180 days
Secondary	Intra-operative blood product usage		1 day
Secondary	Death from any cause		180 days
Secondary	Total costs for initial transplant hospitalization		up to 180 days