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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Recruitment Status : Withdrawn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

Tracking Information
First Submitted Date  ICMJE October 19, 2012
First Posted Date  ICMJE June 21, 2013
Last Update Posted Date June 21, 2013
Study Start Date  ICMJE June 2008
Estimated Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2013)
  • Duration of the initial hospitalization (days) following transplantation [ Time Frame: up to 180 days ]
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2013)
  • Serum AST and alanine transaminase (ALT ) levels after transplant (Peak and Area Under the Curve [AUC]) [ Time Frame: 7 days ]
  • Primary allograft nonfunction defined as patient death or retransplant within 30 days due to liver failure [ Time Frame: 30 days ]
  • Graft survival [ Time Frame: 30 days, 90 days and 180 days ]
  • Subject survival at [ Time Frame: Day 30, 90, and 180 ]
  • Post-transplant renal function [ Time Frame: 30 days ]
  • Duration of time spent in the intensive care unit (ICU; days) during the initial hospitalization. [ Time Frame: up to 180 days ]
  • Intra-operative blood product usage [ Time Frame: 1 day ]
  • Death from any cause [ Time Frame: 180 days ]
  • Total costs for initial transplant hospitalization [ Time Frame: up to 180 days ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Perioperative Remodulin® in Orthotopic Liver Transplant Recipients
Official Title  ICMJE A Single Center, Randomized, Double-Blind, Parallel Placebo-Controlled Study of the Safety and Efficacy of Perioperative Remodulin® in Orthotopic Liver Transplant Recipients
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Liver Transplant
Intervention  ICMJE
  • 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
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: 1
    Intervention: Drug: treprostinil sodium
  • Placebo Comparator: 2
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: June 20, 2013)
0
Original Actual Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2010
Estimated Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01884038
Other Study ID Numbers  ICMJE RIV-LT-301
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party United Therapeutics
Study Sponsor  ICMJE United Therapeutics
Collaborators  ICMJE University of Pittsburgh
Investigators  ICMJE
Principal Investigator: Amadeo Marcos, MD University of Pittsburgh Medical Center
Principal Investigator: Raman Venkataramanan, Ph.D, F.C.P. University of Pittsburgh Medcial Center
PRS Account United Therapeutics
Verification Date June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP