NCT00876902

YSPSL for Prevention of Ischemic Reperfusion Injury in Patients Undergoing Cadaveric Orthotopic Liver Transplantation

A Controlled, Prospective, Blinded, Randomized, Single-Center, Study of YSPSL for Prevention of Ischemic Reperfusion Injury in Patients Undergoing Cadaveric Orthotopic Liver Transplantation

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 36 (actual)
• Sponsor: Y's Therapeutics, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The study is designed to assess the feasibility of evaluating YSPSL for the amelioration of ischemia reperfusion injury following liver transplantation by administering YSPSL into the liver graft directly ex vivo via the portal vein and to the recipient intravenously prior to reperfusion. This study is an extension of the recent pilot study YSPSL-0002 with an almost identical study protocol. The rationale of this and the previous study is based on the recent observation that P-selectin expression has been associated in liver grafts with prolonged cold storage times and rejection. By examining biomarkers of IRI including P-selectin by immunohistochemistry and/or quantitative PCR, liver histology and hepatic blood flow using established techniques, the goal of this study is to evaluate the feasibility of using these modalities for future studies of safety and efficacy.

Detailed description

YSPSL-0003 is an extension into 36 patients of the previous 12 patient pilot study YSPSL-0002 under an almost identical study protocol with extended inclusion criteria. Like YSPSL-0002, YSPSL-0003 is a single-center (UCLA), randomized, placebo-controlled, double-blind study. Patients are randomly assigned to either active study drug (Active group) or placebo (Control group) prior to transplantation. The active study drug dose includes both a 1 mg/kg IV infusion for the recipient and a 20 mg \[approximately 0.27 mg/kg\] as an ex vivo flush. The doses are administered via 2 separate infusions of study agent: one 20 mg dose into the portal vein of the liver prior to implantation as an ex vivo flush with Viaspan®; and the second infusion of 1 mg/kg intravenously into the recipient, when technically feasible, prior to the hepatic artery anastomosis. Placebo of a volume equivalent to active study drug is prepared for administration to the control group to help maintain the blind. Those patients that experience an intraoperative blood loss of \>10 units, receive an additional 1 mg/kg IV infusion of study agent (or placebo equivalent) at the end of the transplant surgery. The Investigator/Sponsor is blinded to the treatment assignment for each patient. Randomization assignment is maintained by UCLA's clinical pharmacist.

Conditions

• Ischemia Reperfusion Injury

Interventions

Type	Name	Description
DRUG	recombinant P-selectin glycoprotein ligand Ig fusion protein	The active study drug dose includes both a 1 mg/kg IV infusion for the recipient and a 20 mg \[approximately 0.27 mg/kg\] as an ex vivo flush. The doses will be administered via 2 separate infusions of study agent: one 20 mg dose into the portal vein of the liver prior to implantation as an ex vivo flush with Viaspan®; and the second infusion of 1 mg/kg intravenously into the recipient, when technically feasible, prior to the hepatic artery anastomosis. Those patients that experience an intraoperative blood loss of \>10 units, will receive an additional 1 mg/kg IV infusion of study agent at the end of the transplant surgery.
DRUG	Viaspan® and saline	Placebo of a volume equivalent to active study drug will be prepared for administration to the control group to help maintain the blind. Those patients that experience an intraoperative blood loss of \>10 units, will receive an additional 1 mg/kg IV infusion of placebo equivalent at the end of the transplant surgery.

Timeline

• Start date: 2008-05-01
• Primary completion: 2009-03-01
• Completion: 2009-10-01
• First posted: 2009-04-07
• Last updated: 2009-04-07

Locations

1 site across 1 country: United States