Clinical Evaluation of the Safety and Preliminary Efficacy of Continuous Infusion of Treprostinil to Prevent Ischemia and Reperfusion Injury in Adult Orthotopic Liver Transplant Recipients.
1Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA
2Thomas Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA
3Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA
4Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA
Meeting: 2017 American Transplant Congress
Abstract number: 252
Keywords: Graft function, Ischemia, Liver transplantation, Survival
Session Information
Session Name: Concurrent Session: Liver Retransplantation and Other Complications
Session Type: Concurrent Session
Date: Monday, May 1, 2017
Session Time: 2:30pm-4:00pm
Presentation Time: 3:30pm-3:42pm
Location: E353B
Introduction:
Liver transplantation is currently the only therapeutic option for patients with end stage liver diseases. Liver allografts undergo cold ischemic injury and warm reperfusion injury during preservation and transplantation procedure, respectively, which is known as ischemia reperfusion injury. We hypothesize that treprostinil, a stable prostacyclin analog, can be safely administered to the liver transplant patients who are hemodynamically stable, and predict that treprostinil will ameliorate ischemia reperfusion injury due to its vasodilatory and antiplatelet activity and ability to down-regulate pro-inflammatory cytokines.
Methods:
This study is a pilot single center, open-label, dose-escalation phase I/II study with outpatient follow-up for up to 180 days. Treprostinil was administered IV as a continuous infusion for 120 hrs after the patient is hemodynamically stable following the placement of new liver graft.
Results:
8 patients have completed the study and were dosed at 3 different infusion rates; 5 ng/kg/min for 48 hrs and 2.5 and 5 ng/kg/min for 120 hrs. Patients safety profile was documented by assessing: mPAP, CO, CI, HR, SBP and DBP. None of the hemodynamic parameters were affected by treprostinil and were within normal ranges. During the first 7 days after liver transplantation, total bilirubin, ALT and AST gradually reduced to normal levels in all patients. 95% of indocyanine green plasma disappearance rate values at day 2 and 5 of our patients were >18%/min (normal healthy subject value), indicating that treprostinil improved the hepatic uptake and hepatobiliary excretory capacity. All subjects and grafts survived throughout the study period (180 days).
Conclusion:
Our study shows that treprostinil can be safely given to liver transplant patients and appears to minimize hepatic ischemia and reperfusion injury.
CITATION INFORMATION: Almazroo O, Miah M, Pillai V, Humar A, Tevar A, Hughes C, AlKhafaji A, Demetris A, Dermont S, Fedorek S, Johnson H, Lopez R, Planinsic R, Sengupta B, Sethu I, Sturdevant M, Ziobert S, Venkataramanan R. Clinical Evaluation of the Safety and Preliminary Efficacy of Continuous Infusion of Treprostinil to Prevent Ischemia and Reperfusion Injury in Adult Orthotopic Liver Transplant Recipients. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Almazroo O, Miah M, Pillai V, Humar A, Tevar A, Hughes C, AlKhafaji A, Demetris A, Dermont S, Fedorek S, Johnson H, Lopez R, Planinsic R, Sengupta B, Sethu I, Sturdevant M, Ziobert S, Venkataramanan R. Clinical Evaluation of the Safety and Preliminary Efficacy of Continuous Infusion of Treprostinil to Prevent Ischemia and Reperfusion Injury in Adult Orthotopic Liver Transplant Recipients. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/clinical-evaluation-of-the-safety-and-preliminary-efficacy-of-continuous-infusion-of-treprostinil-to-prevent-ischemia-and-reperfusion-injury-in-adult-orthotopic-liver-transplant-recipients/. Accessed May 10, 2025.« Back to 2017 American Transplant Congress