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

NCT01884038 | Withdrawn Phase 2 DMC

• 1 other identifier: RIV-LT-301
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Transplant

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Duration of the initial hospitalization (days) following transplantation

  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.

  7 days

Secondary Outcomes (9)

• Serum AST and alanine transaminase (ALT ) levels after transplant (Peak and Area Under the Curve [AUC])

  7 days

• Primary allograft nonfunction defined as patient death or retransplant within 30 days due to liver failure

  30 days

• Graft survival

  30 days, 90 days and 180 days

• Subject survival at

  Day 30, 90, and 180

• Post-transplant renal function

  30 days

Study Arms (2)

Remodulin

EXPERIMENTAL

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.

Drug: treprostinil sodium

Placebo

PLACEBO COMPARATOR

Matching placebo

Drug: Placebo

Interventions

treprostinil sodium 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

Also known as: Remodulin, UT 15

Remodulin

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• United Therapeutics: lead
• University of Pittsburgh Medical Center: collaborator

Study Sites (1)

University of Pittsburgh Medical Center, Starzl Transplantation Institute

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Reperfusion Injury

Interventions

treprostinil

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Amadeo Marcos, MD

  University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

• Raman Venkataramanan, Ph.D, F.C.P.

  University of Pittsburgh Medcial Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2012
• First Posted: June 21, 2013
• Study Start: June 1, 2008
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: December 19, 2023

Record last verified: 2013-06

Locations

US (1)