search
Back to results

Safety and Efficacy of Treprostinil in Ischemia and Reperfusion Injury in Adult Orthotopic Liver Transplantation

Primary Purpose

Ischemia Reperfusion Injury

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Treprostinil
Sponsored by
Abhinav Humar, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemia Reperfusion Injury focused on measuring liver transplantation, treprostinil

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Have signed appropriate informed consent.
  2. Be between 18 years and 65 years of age.
  3. Have been accepted as a liver transplant candidate at the University of Pittsburgh Medical center (UPMC).
  4. Be receiving a cadaver donor liver transplant.
  5. Be treated in accordance with the standard of care protocol(s) currently in effect for liver transplant recipients at the UPMC, including immunosuppression and other elements of pre- and post-operative care.

Exclusion Criteria:

Subjects must not:

  1. Be receiving a living donor liver transplant.
  2. Be receiving a donor liver with a cold ischemia time less than 5 hours or greater than 12 hours.
  3. Be receiving any investigational drug (a drug other than Treprostinil administered under an IND) or participating in any other investigational study, with the exception of alemtuzumab (Campath).
  4. Be receiving any prostanoid to treat portopulmonary hypertension.
  5. Have had a failed liver transplant within the previous 180 days.
  6. Be undergoing multi-organ transplantation (transplantation of organs other than liver at the same time as the liver transplantation procedure).
  7. Have fulminant hepatic failure
  8. Model for end stage liver diseases (MELD) score of > 40
  9. Hepatitis C positive donor liver
  10. On renal replacement therapy at the time of study
  11. Be receiving any non-standard immunosuppression protocol or other non-standard treatment that could affect interpretation of the study results.
  12. Those currently receiving treatment for portopulmonary hypertension.
  13. Those with significant cardiovascular disease including treatment with inotropes.
  14. Have any known hypersensitivity to prostaglandins, prostacyclin or treprostinil.
  15. If female, be pregnant or nursing (as confirmed by urine pregnancy test at Baseline).
  16. HIV positive
  17. Individuals who are allergic to iodine
  18. Individuals who are receiving methylene blue
  19. A donor liver with macrosteatosis greater than 40% if biopsy results are available

Sites / Locations

  • Abhinav Humar
  • University of Pittsburgh Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treprostinil

Arm Description

This is a single center, open-label, dose-escalation Phase I/II study of Treprostinil.

Outcomes

Primary Outcome Measures

Serum ALT concentration after treprostinil treatment in liver transplant patients
The liver injury marker such as alanine aminotransferase (ALT) will be measured in order to evaluate the protective effect of treprostinil in liver transplant recipients.

Secondary Outcome Measures

Pharmacokinetics of treprostinil in liver transplant patients
Clearance and half life

Full Information

First Posted
October 20, 2011
Last Updated
August 3, 2023
Sponsor
Abhinav Humar, MD
search

1. Study Identification

Unique Protocol Identification Number
NCT01481974
Brief Title
Safety and Efficacy of Treprostinil in Ischemia and Reperfusion Injury in Adult Orthotopic Liver Transplantation
Official Title
An Evaluation of the Safety and Preliminary Efficacy of Perioperative Treprostinil in Preventing Ischemia and Reperfusion Injury in Adult Orthotopic Liver Transplant Recipients
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 2012 (undefined)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Abhinav Humar, MD

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The overall purpose of this study is to evaluate the safety, pharmacokinetics and preliminary efficacy of a five-days post-operative course of Treprostinil in liver transplant patients. The hypothesis of this study is that Treprostinil can be safely administered post-operatively in liver transplant patients. Once safety is documented future studies will address its ability to ameliorate or prevent reperfusion mediated dysfunction of the liver graft and thereby reduce morbidity, leading to shorter hospital stays as compared to historical controls.
Detailed Description
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 minimizing the effect of ischemia and re perfusion injury of the liver graft. 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. Routine use of prostaglandins (PGE1 and PGI2), however, was limited by its instability and short half life. Treprostinil, as a prostanoid (prostacyclin analog), is expected to facilitate restoration of the blood supply to the revascularized graft and provide the well-characterized protective effects of this class of compounds in liver transplant patients. Treprostinil has the advantage of a longer elimination half-life than other prostanoids previously tested in these patients. Treprostinil is expected to significantly protect the graft from ischemia and re perfusion injury. This is a pilot study to evaluate the safety, pharmacokinetics and preliminary efficacy of Treprostinil in orthotopic liver transplant patients as a first step to evaluate its use in prevention of ischemia and reperfusion injury of the grafted liver.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemia Reperfusion Injury
Keywords
liver transplantation, treprostinil

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treprostinil
Arm Type
Experimental
Arm Description
This is a single center, open-label, dose-escalation Phase I/II study of Treprostinil.
Intervention Type
Drug
Intervention Name(s)
Treprostinil
Other Intervention Name(s)
Brand name: REMODULIN
Intervention Description
The Treatment Phase will begin at the initiation of Treprostinil after induction of anesthesia for the transplant surgery and continues throughout the surgery and for approximately a total of 120 hours. Treatment phase activities include: • Initiation of Treprostinil after the patient is hemodynamically stable following transplant surgery. (Treprostinil dosing will follow a standard 3 + 3 phase 1 design.
Primary Outcome Measure Information:
Title
Serum ALT concentration after treprostinil treatment in liver transplant patients
Description
The liver injury marker such as alanine aminotransferase (ALT) will be measured in order to evaluate the protective effect of treprostinil in liver transplant recipients.
Time Frame
Day 7
Secondary Outcome Measure Information:
Title
Pharmacokinetics of treprostinil in liver transplant patients
Description
Clearance and half life
Time Frame
0, 2, 4, 6, 12, 18, 24, 30, 36, 42, 48, 72, 96 and 120 hrs during therapy and approximately 0.5, 1, 2, 4, 6, 8, 12 and 24 hr post study drug termination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Have signed appropriate informed consent. Be between 18 years and 65 years of age. Have been accepted as a liver transplant candidate at the University of Pittsburgh Medical center (UPMC). Be receiving a cadaver donor liver transplant. Be treated in accordance with the standard of care protocol(s) currently in effect for liver transplant recipients at the UPMC, including immunosuppression and other elements of pre- and post-operative care. Exclusion Criteria: Subjects must not: Be receiving a living donor liver transplant. Be receiving a donor liver with a cold ischemia time less than 5 hours or greater than 12 hours. Be receiving any investigational drug (a drug other than Treprostinil administered under an IND) or participating in any other investigational study, with the exception of alemtuzumab (Campath). Be receiving any prostanoid to treat portopulmonary hypertension. Have had a failed liver transplant within the previous 180 days. Be undergoing multi-organ transplantation (transplantation of organs other than liver at the same time as the liver transplantation procedure). Have fulminant hepatic failure Model for end stage liver diseases (MELD) score of > 40 Hepatitis C positive donor liver On renal replacement therapy at the time of study Be receiving any non-standard immunosuppression protocol or other non-standard treatment that could affect interpretation of the study results. Those currently receiving treatment for portopulmonary hypertension. Those with significant cardiovascular disease including treatment with inotropes. Have any known hypersensitivity to prostaglandins, prostacyclin or treprostinil. If female, be pregnant or nursing (as confirmed by urine pregnancy test at Baseline). HIV positive Individuals who are allergic to iodine Individuals who are receiving methylene blue A donor liver with macrosteatosis greater than 40% if biopsy results are available
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Abhinav Humar, M.D.
Organizational Affiliation
University of Pittsburgh Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Abhinav Humar
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15261
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15261
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Safety and Efficacy of Treprostinil in Ischemia and Reperfusion Injury in Adult Orthotopic Liver Transplantation

We'll reach out to this number within 24 hrs