A Controlled, Prospective, Blinded, Randomized, Single-Center, Study of YSPSL for Prevention of Ischemic Reperfusion Injury in Patients Undergoing Cadaveric Orthotopic Liver Transplantation
试验速览
- 阶段
- 2 期
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: recombinant P-selectin glycoprotein ligand Ig fusion protein (Drug)
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.
干预措施: Viaspan® and saline (Drug)
结局指标
主要结局
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.
时间窗: 6 months post trasplant
次要结局
- 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.(6 months post transplant)