Study of Tacrolimus vs Mycophenolate Mofetil in Pediatric Patients With Frequently Relapsing or Steroid Dependent Nephrotic Syndrome: a Randomized, Multicenter, Open-label, Parallel-arm Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 270
- 试验地点
- 12
- 主要终点
- 1-year relapse-free survival rate
研究概览
简要总结
Primary nephrotic syndrome accounts for approximately 90% of the total number of nephrotic syndrome in childhood and it is the most common glomerular disease in children. Although treatment with steroids is uesful for primary nephrotic syndrome, proning to cause frequent relapse/steroid-dependent nephrotic syndrome after treatment, and the usage of immunosuppressive agents has become a new choice for the treatment of such patients. This study is a prospective, randomized, multicenter, open, parallel controlled trial, evaluating the efficacy and safety of steroid combined with the immunosuppressive agents which are tacrolimus and mycophenolate mofetil to children who with frequently relapsing or steroid-dependent nephrotic syndrome, all we wish to obtain the proper drug choice and individualized treatment options for children with nephrotic syndrome.
详细描述
Although steroids are recognized as first-line treatments for nephrotic syndrome, the vast majority of children relapse, and about half of them have frequent relapse or steroids dependence after treatment with steroids alone. Some children experienced steroids-resistance after multiple relapses, and eventually developed into chronic kidney dysfunction. Long-term or repeated application of large doses of steroids will lead to side effects such as obesity, growth retardation, and hypertension. Although the treatment of steroids with immunosuppressive agents is a new choice for the treatment of such patients, traditional immunosuppressive agents such as cyclophosphamide and cyclosporine A will bring some serious irreversible side effects, while immunosuppressive agents tacrolimus has the dual effects of immunosuppression and podocyte protection, and is more widely used in the department of nephrology, what's more, the other immunosuppressive agents mycophenolate mofetil has advantage of no kidney toxic, less adverse reactions and higher safety, which gradually being valued by nephrologists in recent years. This study mainly compares the efficacy and safety of tacrolimus and mycophenolate mofetil in the treatment of children with frequently relapsing or steroids-dependent nephrotic syndrome, in order to provide a more effective and safer treatment for children with nephrotic syndrome as well as the therapeutic medication options.
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
- 2 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Sensitive but frequent relapses or steroids dependence nephrotic syndrome
- •Age: 2 to 18 years old
- •Normal renal function: estimated glomerular filtration rate ≥90ml/min/1.73m2
- •Morning urine protein <1+ or urine protein-creatinine ratio <0.2g/g (<20 mg/mmol) for 3 consecutive days and above when in enroll
- •No tacrolimus, mycophenolate mofetil, cyclosporine A, rituximab or cyclophosphamide was used within 2 years prior to the enrollment
排除标准
- •steroids-resistant nephrotic syndrome
- •Family history of nephrotic syndrome, chronic glomerulonephritis or uremia
- •Leukopenia (White Blood Cells ≤ 3.0 * 10^9 / L)
- •Moderate to severe anemia (hemoglobin <9.0 g/dL)
- •Thrombocytopenia (platelet count <100*10^12/L)
- •Positive Hepatitis B virus serological indicators (Hepatitis B surface antigen or / and Hepatitis B virus e antigen or / and Hepatitis B core antibody), Hepatitis C virus-positive or patients with abnormal liver function (2 or more times of alamine aminotransferase or total bilirubin was exceeded the normal value, and continued to rise for 2 weeks)
- •There are chronic active infections such as Epstein-Barrvirus, cytomegalovirus or Mycobacterium tuberculosis, and the usage of steroids and immunosuppressive agents may aggravate the state of an illness
- •Secondary nephrotic syndrome (such as purpuric nephritis, lupus nephritis, etc.)
- •Those who with hematological or endocrine system diseases as well as serious organs illness such as heart, liver or kidney
- •Those who with other autoimmune diseases or primary immunodeficiencies or tumors
- •Those who was known to be sensitized to tacrolimus, mycophenolate mofetil, glucocorticoids, or any of the above drugs
- •Those who have participated in other clinical trials within three months prior to the enrollment
- •Those who was not suitable for participating this study judged by investigator
研究组 & 干预措施
Tacrolimus(Group A)
Tacrolimus: 0.5mg and 1mg; Capsule; 0.05-0.10mg/kg/day，BID; Steroid: 5mg; Oral tablets; 1.0-1.5 mg/kg, qod or 0.5-0.75 mg/kg/day, qd;
干预措施: Tacrolimus (Drug)
Mycophenolate Mofetil(Group B)
Mycophenolate Mofetil: 250mg; Dispersible tablets; 20~30mg/kg/day，BID; Steroid: 5mg; Oral tablets; 1.0-1.5 mg/kg, qod or 0.5-0.75 mg/kg/day, qd;
干预措施: Mycophenolate Mofetil (Drug)
结局指标
主要结局
1-year relapse-free survival rate
时间窗: 1-year period after randomization
The rate of no relapse within 1 year
次要结局
- Relapse of nephrotic syndrome during 12 months after randomization(1-year period after randomization)
- Number of relapses during 12 months follow up(1-year period after randomization)
- Change in renal function of the patients(1-year period after randomization)
- Adverse event(1-year period after randomization)
- The first time to relapse(1-year period after randomization)
- Cumulative prednisone dosage (milligrams per kilogram per year)(1-year period after randomization)
- Change in serum cholesterol, hemoglobin and blood albumin of the patients(1-year period after randomization)
- Change in anthropometry and growth velocity during 12-month period after randomization(1-year period after randomization)
研究者
Mao Jianhua
Chief Physician
The Children's Hospital of Zhejiang University School of Medicine