- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00876902
YSPSL for Prevention of Ischemic Reperfusion Injury in Patients Undergoing Cadaveric Orthotopic Liver Transplantation (YSPSL)
April 6, 2009 updated by: Y's Therapeutics, Inc.
A Controlled, Prospective, Blinded, Randomized, Single-Center, Study of YSPSL for Prevention of Ischemic Reperfusion Injury in Patients Undergoing Cadaveric Orthotopic Liver Transplantation
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.
Study Overview
Status
Unknown
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
36
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
California
-
Los Angeles, California, United States, 90095
- UCLA School of Medicine
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patient will be a recipient of a primary (first) ABO compatible cadaveric liver allograft
- Patient's age is less than 18 years
- Patient is not a recipient of a multivisceral transplant or simultaneous kidney transplant
- Patient has not undergone prior organ or cellular transplant of any type
- Patient has a Model for End Stage Liver Disease (MELD) score of ≤38
- Cold ischemia time (CIT) anticipated to be less than 14 hours
- Donor liver procured by UCLA liver team
- Veno-veno bypass is not planned to be used for the patient (e.g. no prior surgery or other factor that indicates a risk for excessive blood loss and therefore a need for veno-veno bypass +/- autologous recovery during surgery)
- For patients who are women of childbearing potential, patient has a negative pregnancy test (either urine or serum) within 48 hours prior to transplant
- Patient (male and female) is willing to use an acceptable form of birth control for at least 3 months post-treatment
- Patient is willing and able to sign informed consent.
Exclusion Criteria:
- Patient has a prior organ transplant of any type
- Patient has known allergic or intolerance reactions to human immune globulins, antibodies, or components of the formulation or known contraindication to administration of YSPSL
- Patient has an uncontrolled active infection (on antibiotics with controlled infection is not an exclusion)
- Patient has active Hepatitis B virus (HBV)/transplant for HBV related cirrhosis
- Patient has previously participated in this study or another study with YSPSL
- Patient has received investigational therapy within 90 days prior to the transplant procedure
- Patient has current drug or alcohol abuse or, in the opinion of the investigator, is at risk for poor compliance with the visits in this protocol (no drug testing required)
- Patient is a pregnant or nursing female, a female of childbearing potential planning to become pregnant within the duration of this study, or is not practicing birth control
- Patient is planned to receive a living donor liver transplant
- Patient lives >200 miles away or otherwise is not able to participate in study follow-up visits
- Donor body mass index >40
- Donor liver biopsy >40% macrosteatotic fat
- Donor age >70.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1
Active Group: (18 subjects) YSPSL administered as an ex vivo flush (20 mg YSPSL in Viaspan® 200 mL total volume) into the portal vein prior to transplant at the back table; YSPSL 1 mg/kg administered IV to the transplant recipient PRIOR to arterial reperfusion of the liver.
One extra IV dose of 1 mg/kg will be given at the end of the procedure only to patients that have experienced an intraoperative blood loss of greater than 10 units.
|
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.
Other Names:
|
Placebo Comparator: 2
Placebo Control: (18 subjects) Ex vivo flush of placebo control (200 mL Viaspan®) into the portal vein prior to transplant and 0.1 mL/kg placebo control (saline) IV to the transplant recipient PRIOR to arterial reperfusion of the liver.
One additional infusion of 0.1 mL/kg placebo control (saline) will be given at the end of the procedure to patients that have experienced an intraoperative blood loss of greater than 10 units.
|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Safety will be evaluated by clinical and laboratory assessments, an abbreviated pharmacokinetic (PK) profile of the administered dose of YSPSL, and graft function and patient and graft survival through 6 months post-transplant.
Time Frame: 6 months post trasplant
|
6 months post trasplant
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To evaluate the potential efficacy of prophylaxis with YSPSL on ischemia reperfusion injury (IRI) as assessed by proposed efficacy evaluations of IRI in liver transplants, in patients who meet eligibility criteria for the trial.
Time Frame: 6 months post transplant
|
6 months post transplant
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Stefan Hemmerich, PhD, Y's Therapeutics, Inc.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Amersi F, Farmer DG, Shaw GD, Kato H, Coito AJ, Kaldas F, Zhao D, Lassman CR, Melinek J, Ma J, Volk HD, Kupiec-Weglinski JW, Busuttil RW. P-selectin glycoprotein ligand-1 (rPSGL-Ig)-mediated blockade of CD62 selectin molecules protects rat steatotic liver grafts from ischemia/reperfusion injury. Am J Transplant. 2002 Aug;2(7):600-8. doi: 10.1034/j.1600-6143.2002.20704.x.
- Busuttil RW, Lipshutz GS, Kupiec-Weglinski JW, Ponthieux S, Gjertson DW, Cheadle C, Watkins T, Ehrlich E, Katz E, Squiers EC, Rabb H, Hemmerich S. rPSGL-Ig for improvement of early liver allograft function: a double-blind, placebo-controlled, single-center phase II study. Am J Transplant. 2011 Apr;11(4):786-97. doi: 10.1111/j.1600-6143.2011.03441.x. Epub 2011 Mar 14.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2008
Primary Completion (Actual)
March 1, 2009
Study Completion (Anticipated)
October 1, 2009
Study Registration Dates
First Submitted
April 3, 2009
First Submitted That Met QC Criteria
April 6, 2009
First Posted (Estimate)
April 7, 2009
Study Record Updates
Last Update Posted (Estimate)
April 7, 2009
Last Update Submitted That Met QC Criteria
April 6, 2009
Last Verified
April 1, 2009
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Postoperative Complications
- Ischemia
- Wounds and Injuries
- Reperfusion Injury
- Physiological Effects of Drugs
- Anti-Infective Agents
- Antiviral Agents
- Antineoplastic Agents
- Immunologic Factors
- Protective Agents
- Adjuvants, Immunologic
- Antibiotics, Antineoplastic
- Interferon Inducers
- Radiation-Protective Agents
- polysaccharide-K
Other Study ID Numbers
- YSPSL-0003-PF.3
- IND 101,040
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Ischemia Reperfusion Injury
-
University of ChileFondo Nacional de Desarrollo Científico y Tecnológico, ChileCompletedReperfusion Injury | Acute Myocardial Infarction | Ischemia-reperfusion Injury | Reperfusion Injury, Myocardial | Reperfusion ArrhythmiasChile
-
University of AarhusErasmus Medical Center; Fonden til Lægevidenskabens FremmeCompletedIschemia Reperfusion Injury | Ischaemia Reperfusion InjuryDenmark
-
Samsung Medical CenterCompletedIschemia/Reperfusion Injury of Liver Graft | Ischemia/Reperfusion Injury of Kidney | Remote Ischemic PostconditioningKorea, Republic of
-
Shahid Beheshti University of Medical SciencesPooyesh DarouCompletedMyocardial Ischemic Reperfusion InjuryIran, Islamic Republic of
-
Tambi JarmiWithdrawn
-
University of PennsylvaniaActive, not recruiting
-
José García de la AsunciónCompleted
-
Medical University InnsbruckUnknownIschemia Reperfusion Injury
-
Aristotle University Of ThessalonikiCompletedIschemia Reperfusion Injury
-
MWolztUnknown
Clinical Trials on recombinant P-selectin glycoprotein ligand Ig fusion protein
-
Y's Therapeutics, Inc.Completed
-
Y's Therapeutics, Inc.Completed
-
Y's Therapeutics, Inc.UnknownLiver DiseasesUnited States
-
Huabo Biopharm Co., Ltd.Recruiting
-
National Cancer Institute (NCI)CompletedMelanoma | Stage III Cutaneous Melanoma AJCC v7 | Stage IV Cutaneous Melanoma AJCC v6 and v7 | Ocular Melanoma | Stage IIIC Cutaneous Melanoma AJCC v7 | Melanoma of Unknown Primary | Cutaneous Melanoma | Mucosal Melanoma | Stage IIIA Cutaneous Melanoma AJCC v7 | Stage IIIB Cutaneous Melanoma AJCC v7 | Stage... and other conditionsUnited States