Safety and Efficacy of Treprostinil in Ischemia and Reperfusion Injury in Adult Orthotopic Liver Transplantation
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|ClinicalTrials.gov Identifier: NCT01481974|
Recruitment Status : Recruiting
First Posted : November 30, 2011
Last Update Posted : February 13, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Ischemia Reperfusion Injury||Drug: Treprostinil||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 Start Date :||December 2012|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2018|
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 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.
Other Name: Brand name: REMODULIN
- Serum ALT concentration after treprostinil treatment in liver transplant patients [ Time Frame: Day 7 ]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.
- Pharmacokinetics of treprostinil in liver transplant patients [ 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 ]Clearance and half life
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01481974
|Contact: Abhinav Humar, M.D.||email@example.com|
|United States, Pennsylvania|
|Pittsburgh, Pennsylvania, United States, 15261|
|Sub-Investigator: Raman Venkataramanan, Ph.D.|
|Sub-Investigator: Roberto C Lopez, M.D.|
|Sub-Investigator: Anthony Demetris, M.D.|
|Sub-Investigator: Raymond Planinsic, M.D.|
|Sub-Investigator: Heather Johnson, Pharm.D.|
|Sub-Investigator: Sheila Fedorek, R.N. CCRC|
|Sub-Investigator: Stephanie Dermont, R.N.|
|Sub-Investigator: Christopher Hughes, M.D.|
|Sub-Investigator: Ali H Al-Khafaji, M.D.|
|Sub-Investigator: Omar A Almazroo, Ph.D. CCTR|
|Sub-Investigator: Amit Tevar, M.D.|
|Sub-Investigator: Staci Ziobert, Pharm.D.|
|Sub-Investigator: Md Kowser Miah, Ph.D.|
|Sub-Investigator: Swaytha Ganesh, M.D.|
|Sub-Investigator: Michele Molinari, M.D.|
|Sub-Investigator: Imam Hussain Shaik, Ph.D.|
|University of Pittsburgh Medical Center||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15261|
|Contact: ABHINAV HUMAR, MD|
|Principal Investigator:||Abhinav Humar, M.D.||University of Pittsburgh|