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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by University of Pittsburgh
Sponsor:
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01481974
First received: October 20, 2011
Last updated: October 18, 2013
Last verified: October 2013
  Purpose

The overall purpose of this study is to evaluate the safety, pharmacokinetics and preliminary efficacy of a two-day peri-operative course of Treprostinil in liver transplant patients.

The hypothesis of this study is that Treprostinil can be safely administered perioperatively 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.


Condition Intervention Phase
Ischemia Reperfusion Injury
Drug: Treprostinil
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Serum ALT concentration after treprostinil treatment in liver transplant patients [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]
    The liver injury marker such as 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 [ Time Frame: 2, 4, 6, 12, 18, 24, 30, 36, 42, 48 hrs during therapy and approximately 0.5, 1, 2, 4, 6, 8, 12 and 24 hr post study drug termination ] [ Designated as safety issue: Yes ]
    Clearance and half life


Estimated Enrollment: 30
Study Start Date: December 2012
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treprostinil
This is a single center, open-label, dose-escalation Phase I/II study of Treprostinil.
Drug: Treprostinil

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 48 hours.

Treatment phase activities include:

• Initiation of Treprostinil after induction of anesthesia for the transplant surgery. (Treprostinil dosing will follow a standard 3 + 3 phase 1 design.

Other Name: Brand name: REMODULIN

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 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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 6 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. MELD score of > 35
  9. Hepatitis C positive donor liver
  10. On inotropes at the time of the study
  11. On renal replacement therapy at the time of study
  12. Be receiving any non-standard immunosuppression protocol or other non-standard treatment that could affect interpretation of the study results.
  13. Those currently receiving treatment for portopulmonary hypertension.
  14. Those with significant cardiovascular disease.

16. 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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01481974

Contacts
Contact: Abhinav Humar, M.D. 412-692-4553 humara2@upmc.edu

Locations
United States, Pennsylvania
Abhinav Humar Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15261
Sub-Investigator: Raman Venkataramanan, PhD         
Sub-Investigator: Paulo Fontes, M.D.         
Sub-Investigator: Ruy J Cruz, M.D., PhD         
Sub-Investigator: Mark L Sturdevant, M.D.         
Sub-Investigator: Roberto C Lopez, M.D.         
Sub-Investigator: Anthony Demetris, M.D.         
Sub-Investigator: Raymond Planinsic, M.D.         
Sub-Investigator: Venkateswaran Chithambaram Pillai, PhD         
Sub-Investigator: Heather Johnson, Pharm.D.         
Sub-Investigator: Tracy Grogan         
Sub-Investigator: Sheila Fedorek, RN CCRC         
Sub-Investigator: Laurie Hope, R.N.         
Sub-Investigator: Stephanie Dermont, R.N.         
Sub-Investigator: Christopher Hughes, M.D.         
Sub-Investigator: Al H Al-Khafaji, M.D.         
Sub-Investigator: Vikram Raghu         
Sub-Investigator: Juan Megia         
Sub-Investigator: Edgar Ramos         
Sub-Investigator: Dilip Suryavanshi         
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15261
Contact: ABHINAV HUMAR, MD         
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Abhinav Humar, M.D. University of Pittsburgh
  More Information

No publications provided

Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01481974     History of Changes
Other Study ID Numbers: PRO10050268
Study First Received: October 20, 2011
Last Updated: October 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:
liver transplantation
treprostinil

Additional relevant MeSH terms:
Ischemia
Reperfusion Injury
Wounds and Injuries
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications
Treprostinil
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014