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

NCT ID: NCT01884038

Last Updated: 2023-12-19

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2/PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2010-06-30

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.

Conditions

Liver Transplant

Keywords

Liver Transplant; Prostacyclin; Treprostinil sodium; Remodulin; Reperfusion Injury; Primary Nonfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

treprostinil sodium

Intervention Type: DRUG

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

Matching placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

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

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Remodulin; UT 15

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pittsburgh Medical Center

OTHER

Sponsor Role: collaborator

United Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amadeo Marcos, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh Medical Center

Raman Venkataramanan, Ph.D, F.C.P.

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh Medcial Center

Locations

University of Pittsburgh Medical Center, Starzl Transplantation Institute

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

RIV-LT-301

Identifier Type: -

Identifier Source: org_study_id