A Prospective, Open Label, Pilot Study Comparing the Use of Low-target Advagraf With Rabbit Antithymocyte Globulin Induction Versus Conventional Target Advagraf With Basiliximab Induction in a Steroid-avoidance Immunosuppressive Protocol for de Novo Renal Transplant Recipients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Number of Participants With New Onset Diabetes After Transplant (NODAT) or Acute Rejection
研究概览
简要总结
While the incidence of acute rejection and early graft loss have improved dramatically with the advent of newer immunosuppressant medications, improvements in long-term patient and allograft survival after kidney transplantation have not been achieved. The specific drug combination that provides the best outcomes with the least amount of side effects is not known. Each kidney transplant center uses the combination of drugs that they believe is optimal. This study is about identifying whether drugs that are currently approved for use in kidney transplantation can be used in a new combination safely and with potentially fewer side effects than the drug combinations that are currently used at St. Paul's Hospital and other transplant centres.
详细描述
Purpose This study has been designed to test whether using Thymoglobulin with low dose tacrolimus and early steroid withdrawal will minimize both kidney rejection and the development of new onset diabetes after transplant (NODAT).
Justification Experimental treatment is low target tacrolimus with thymoglobulin. Standard treatment is a standard target (higher dose) tacrolimus and basiliximab, instead of thymoglobulin.
The investigators hypothesize, that a combined approach of early steroid withdrawal and low dose tacrolimus in low immunologic risk transplant recipients will be effective in reducing the incidence of new onset diabetes mellitus, while maintaining a low risk of acute rejection.
Objective
The objective of this study is to compare early post-transplant outcomes with the use of low target versus standard target Advagraf in de novo kidney allograft recipients of low immunologic risk undergoing early corticosteroid withdrawal.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients over 18 years of age who receive a deceased, living unrelated or living related donor renal transplant
- •No history of pre-existing diabetes mellitus
- •Not using diabetic medications (insulin, hypoglycemic agents) at the time of transplantation
- •Random plasma glucose level <11.1 at the time of transplantation
- •Peak PRA (panel reactive antibody) <30%
- •Females capable of becoming pregnant must have a negative pregnancy test at baseline and are required to practice an approved method of birth control for the duration of the study and for a period of three months following discontinuation of study medication
- •The patient has given written informed consent to participate in the study
排除标准
- •Patients with primary non-function
- •Peak PRA>=30%
- •Multiple organ transplants
- •HLA (human leukocyte antigen) identical living donor transplant recipients
- •Cold ischemia time over 36 hours
- •Nonheart beating donor kidney recipients
- •Pediatric donor kidney recipients
- •Donor age>=65 years
- •Patients who are known to have a positive hepatitis C serology, who are human immunodeficiency virus (HIV) or Hepatitis B surface antigen positive. Laboratory results obtained within 6 months prior to study entry are acceptable. Recipients of organs from donors who test positive for Hepatitis B surface antigen or Hepatitis C will be excluded.
- •Patients who are Epstein-Barr virus (EBV) negative and are receiving a transplant from an EBV-positive donor (mismatch).
- •Presence of any severe allergy requiring acute (within 4 weeks of baseline) or chronic treatment, or hypersensitivity to drugs similar to those used in the study
- •Patients with systemic infections
- •Existence of any surgical or medical condition, other than the current transplant, which in the opinion of the investigator, preclude enrollment in this trial
- •Inability to cooperate or communicate with the investigator
研究组 & 干预措施
Low target tacrolimus (Advagraf)
This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf.
干预措施: Tacrolimus (Drug)
Standard target tacrolimus (Advagraf)
This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Number of Participants With New Onset Diabetes After Transplant (NODAT) or Acute Rejection
时间窗: 6 months post transplant
Composite endpoint of biopsy proven acute rejection and NODAT at 6 months post transplantation. NODAT will be defined as either FPG \>7.0mmol/L OR symptoms of hyperglycemia and a random plasma glucose of \>11.1 OR 2-h plasma glucose \>11.1 during an oral glucose tolerance test(OGTT).
次要结局
- Number of Participant Deaths(6 months post transplant)
- Number of Participants With Graft Failure(6 months post transplant)
- Number of Participants With Dialysis Events(6 months post transplant)
- Number of Participants With Infection Events(6 months post transplant)
- Number of Participants With Hospitalization Events(6 months post transplant)
- Number of Participants With Malignancy Events(6 months post transplant)
- Number of Participants With Cardiovascular Event(6 months post transplant)
- Number of Any Leukopenia Events(6 months post transplant)
- Number of Leukopenia Events on ≥2 Occasions(6 months post transplant)
- Change From Baseline in Weight(baseline to 6 months post transplant)
- eGFR at 6 Months(6 months post transplant)
研究者
Jagbir Gill
Assistant Professor
University of British Columbia