A Study in Adults on Pre LT Dialysis With Basiliximab, Delayed Tacrolimus (TAC), Mycophenolate (MMF), Steroids (Grp 1) vs. Basiliximab, Delayed TAC, MMF, Steroids, With Everolimus 30d Post LT(Grp 2), vs. TAC, MMF, Steroids (Grp 3).
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 71
- 试验地点
- 1
- 主要终点
- Participants Who Have Recovered Renal Function
研究概览
简要总结
This is a study to help understand how well new combinations of immunosuppressive medications (medications that weaken your immune system to prevent your body from rejecting the transplanted liver) work compared to standard immunosuppressive medications after your liver transplant. Also the study will assess how safe the new combination of immunosuppressive medicines are and if there are any changes in how your kidneys work after taking these medicines.
详细描述
A single center, open label, randomized, prospective, pilot study of induction and maintenance immunosuppression in adult subjects >18 years undergoing orthotopic liver transplantation (OLT) with Basiliximab, delayed dose tacrolimus plus mycophenolate mofetil and standard of care (SOC) corticosteroids (Group 1) versus basiliximab, delayed dose tacrolimus plus mycophenolate mofetil, SOC corticosteroids, with addition of delayed maintenance Everolimus at one month post OLT with subsequent mycophenolate mofetil minimization (Group 2) versus standard dose tacrolimus plus mycophenolate mofetil plus SOC corticosteroids (Group 3; control) with concomitant renal dysfunction prior to OLT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 78 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients eligible for inclusion in this study have to fulfill all of the following criteria:
- •A signed informed consent prior to patient participation in the study and before any assessment is performed.
- •Patients who are able to take oral medication.
- •18 years old
- •Undergoing first OLT
- •Dialysis for 45 days or less at time of transplant
- •Able and willing to conform to requirements of the study
- •Able and willing to provide informed consent
排除标准
- •< 18 years old
- •Autoimmune liver disease, Primary Sclerosing Cholangitis, Primary Biliary Cirrhosis
- •Dialysis greater than 45 days
- •Receiving ATG, IVIG therapy, or sirolimus/everolimus around time of transplant or sirolimus/everolimus after transplant
- •Unable to take oral medications
- •Participating in another clinical research study involving the evaluation of another investigational drug or device
- •Documented allergy to basiliximab, TAC, MMF or any macrolide antibiotic.
- •Presence of thrombosis of any major hepatic arteries
- •Complex/high risk arterial reconstruction at any time (graft vessel patency by Doppler ultrasound confirmed and documented).
- •Patients who are recipients of multiple solid organ transplants, (e.g., multivisceral or combined liver-kidney transplants), or have previously received an organ or tissue transplanted, or who received an ABO incompatible transplant.
- •Patients who have severe hypercholesterolemia (>215 mg/dL; >5.5 mmol/L) or hypertriglyceridemia (>265 mg/dL; >3.0 mmol/L) at Baseline.
- •Patients who have severe thrombocytopenia or neutropenia (platelet count >20 and MLCs>1000)
- •Patients who have any surgical or medical condition, which in the opinion of the investigator, might significantly alter the absorption, distribution, metabolism and excretion of study drugs
- •Patients with a known hypersensitivity to the drugs used on study or their class, or to any of the excipients.
- •Patients with clinically significant systemic infection
- •Pregnant or nursing (lactating) female patients, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive βHCG laboratory test (>9 mIU/mL) at Baseline.
研究组 & 干预措施
basiliximab with Delayed TAC
basiliximab
- Dose #1: 20mg IV within 2 hours of transplant
- Dose #2: 20mg IV Post-operative day #4
Tacrolimus (with basiliximab induction) o Beginning day #5 post-transplant or when SCr < 1.8 mg/dl (subjects off dialysis) to six months: 0.03-0.1mg/kg q12h PO to maintain whole blood trough concentration of 4-6ng/mL
Mycophenolate mofetil
o 1000 mg po bid
Corticosteroids (SOC): Per UCLA protocol
Post-operative taper:
- Post-op day 1- methylprednisolone 50mg IVP Q6H
- Post-op day 2- methylprednisolone 40mg IVP Q6H
- Post-op day 3- methylprednisolone 30mg IVP Q6H
- Post-op day 4- methylprednisolone 20mg IVP Q6H
- Post-op day 5- methylprednisolone 20mg IVP Q12H
- Post-op day 6- methylprednisolone 10mg IVP Q12H until taking PO, then change to: prednisone 20mg PO QAM
干预措施: Basiliximab 20 MG (Drug)
basiliximab, Delayed TAC with Everolimus
basiliximab
Tacrolimus (with basiliximab induction)
o Beginning day #5 post-transplant or when SCr < 1.8 mg/dl (subjects off dialysis) to POD 30: 0.03-0.1mg/kg q12h PO to maintain whole blood trough concentration of 4-6ng/mL
Mycophenolate mofetil o 1000 mg po bid up to POD 30: reduce mycophenolate mofetil following achievement of steady state everolimus (POD 35) as clinically indicated
Corticosteroids (SOC): Per UCLA protocol
Everolimus (delayed)
o Add by POD 30: 1 mg po bid and adjusted to maintain whole blood trough concentrations of 3-8 ng/ml.
干预措施: Basiliximab 20 MG (Drug)
结局指标
主要结局
Participants Who Have Recovered Renal Function
时间窗: 6 months
Assessment of dialysis independence (patients no longer requiring dialysis post LT)
次要结局
未报告次要终点
研究者
Fady M Kaldas, M.D., F.A.C.S.
Clincal Professor of Surgery
University of California, Los Angeles