Safety and Efficacy of Treprostinil in Ischemia and Reperfusion Injury in Adult Orthotopic Liver Transplantation
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.
|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|
- 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.
- 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
|Study Start Date:||December 2012|
|Estimated Study Completion Date:||July 2015|
|Estimated Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
This is a single center, open-label, dose-escalation Phase I/II study of 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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01481974
|Contact: Abhinav Humar, M.D.||firstname.lastname@example.org|
|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|
|Principal Investigator:||Abhinav Humar, M.D.||University of Pittsburgh|