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

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ClinicalTrials.gov Identifier: NCT01884038
Recruitment Status : Withdrawn
First Posted : June 21, 2013
Last Update Posted : June 21, 2013
Sponsor:
Collaborator:
University of Pittsburgh
Information provided by (Responsible Party):
United Therapeutics

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.

Condition or disease Intervention/treatment Phase
Liver Transplant Drug: treprostinil sodium Drug: Placebo Phase 2 Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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 Start Date : June 2008
Estimated Primary Completion Date : June 2010
Estimated Study Completion Date : June 2010

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 1 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

Other Names:
  • Remodulin
  • UT 15

Placebo Comparator: 2 Drug: Placebo



Primary Outcome Measures :
  1. Duration of the initial hospitalization (days) following transplantation [ Time Frame: up to 180 days ]
  2. Area under the curve (AUC) of serum aspartate transaminase (AST) levels. [ Time Frame: 7 days ]
    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.


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


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01884038


Locations
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United States, Pennsylvania
University of Pittsburgh Medical Center, Starzl Transplantation Institute
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
United Therapeutics
University of Pittsburgh
Investigators
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Principal Investigator: Amadeo Marcos, MD University of Pittsburgh Medical Center
Principal Investigator: Raman Venkataramanan, Ph.D, F.C.P. University of Pittsburgh Medcial Center

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Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT01884038     History of Changes
Other Study ID Numbers: RIV-LT-301
First Posted: June 21, 2013    Key Record Dates
Last Update Posted: June 21, 2013
Last Verified: June 2013

Keywords provided by United Therapeutics:
Liver Transplant
Prostacyclin
Treprostinil sodium
Remodulin
Reperfusion Injury
Primary Nonfunction

Additional relevant MeSH terms:
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Treprostinil
Antihypertensive Agents