Phase 4 Randomized, Controlled Study Comparing Sirolimus and Mycophenolate Mofetil to Prevent or Reverse Progression in Pediatric Renal Transplants With Chronic Allograft Nephropathy
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- histological quantification of interstitial fibrosis at 2 years
研究概览
简要总结
The purpose of this study is to determine whether treatment with sirolimus, in combination with low-dose tacrolimus and prednisone, is effective for the treatment of chronic allograft nephropathy (progressive scarring) in children who have previously received a kidney transplant. This treatment is compared to the standard therapy which uses low-dose tacrolimus, mycophenolate mofetil and prednisons.
This study is a pilot study that will determine whether treatment with sirolimus reduces or improves the rate of scarring seen on kidney biopsy of the transplanted kidney over time, compared to children who continue to be treated with mycophenolate mofetil.
详细描述
PROTOCOL SYNOPSIS
Title Of Study: A Single Center, Prospective, Randomized, Controlled Study Of Two Chronic Immunosuppressive Protocols Using Sirolimus Or Mycophenolate Mofetil To Prevent Or Reverse Disease Progression In Pediatric Renal Transplants With Chronic Allograft Nephropathy
Short Title: Winnipeg-CAN-1
Clinical Trial: Phase-IV
Objectives: This prospective, randomized, controlled study will evaluate the effectiveness of two different chronic immunosuppressive protocols in the treatment of chronic allograft nephropathy (CAN) in children. One protocol will continue with standard immunosuppression which includes mycophenolate mofetil (MMF), and the other will substitute MMF with sirolimus.
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
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All male or female patients aged less than 17 years.
- •The patient has undergone a kidney transplant, from a cadaveric or living donor with compatible ABO blood type.
- •The patient is more than 12 months post-transplantation.
- •The allograft demonstrates histological changes consistent with CAN according to the Banff 97 classification schema (minimum of ct1 and ci1 score for tubular atrophy and interstitial fibrosis respectively).
排除标准
- •The patient, or in case the patient is minor, the patient's parent(s) or their legal representative, has been fully informed and will not give informed consent to participate in the study.
- •The allograft demonstrates histological changes at the time of enrollment consistent with acute allograft rejection Grade Ia or worse, according to the Banff 97 classification schema (minimum of t2 and i2 score for tubulitis and interstitial inflammation respectively).
- •The patient is known to be allergic or intolerant to MMF, sirolimus or any of their known metabolites.
- •The patient for who routine protocol kidney biopsy is contraindicated.
- •Patients whose maintenance immunosuppression does not include both tacrolimus and prednisone at the time on study enrollment.
- •Patients previously treated with sirolimus.
- •The patient requires ongoing dosing with a systemic immunosuppressive drug at study entry for any reason other than kidney transplantation.
- •The patient and/or donor is known to be HIV or HCV positive.
- •The patient has significant liver disease, defined as having during the past 28 days continuously elevated ASAT (SGOT) and/or ALAT (SGPT) levels greater than 3 times the upper value of the normal range of the investigational site.
- •The patient has persistent leukopenia (WBC <3.0 x109/L).
- •The patient has persistent thrombocytopenia (<100 x109/L).
- •The patient has pre-existing significant hyperlipidemia (total cholesterol >7.8 mmol/L), not responding to medical therapy.
- •The patient has pre-existing elevated triglycerides, not responding to medical therapy.
- •The patient with malignancy or history of malignancy except for successfully treated Wilm's tumor (2 years) or non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully.
- •The patient has significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting or active peptic ulcer.
- •The patient has previously received or is receiving an organ transplant other than kidney.
- •The patient is taking or has been taking an investigational drug in the past 28 days or is currently participating in another clinical intervention trial.
- •Patients with the relapsing, non-diarrheal form of haemolytic-uraemic syndrome.
- •The patient is unlikely to comply with the protocol.
- •The patient has any form of substance abuse, psychiatric disorder or condition which, in the opinion of the investigator, may invalidate communication with the investigator
- •Sexually active female patients who are pregnant or lactating or who do not consent to effective birth control.
- •The patient is less than 6 years of age.
- •The patient has significant and persistent EBV activity as measured by PCR amplification from blood samples.
- •The patient has a prior history of post-transplant lymphoproliferative disease.
结局指标
主要结局
histological quantification of interstitial fibrosis at 2 years
次要结局
- Renal function at 1 and 2 years.
- Proteinuria at 2 years.
- Freedom from acute rejection and graft loss over the 2 year study period.
- Cumulative incidence and prevalence of adverse events and serious adverse events over the 2-year study period.