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

United Therapeutics

Status and phase: Withdrawn; Phase 3; Phase 2

Conditions: Liver Transplant

Treatments: Drug: Placebo; Drug: treprostinil sodium

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01884038

RIV-LT-301

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 2 patient groups, including a placebo group

Remodulin

Experimental group

Description:

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.

Treatment:

Drug: treprostinil sodium

Placebo

Placebo Comparator group

Description:

Matching placebo

Treatment:

Drug: Placebo