Study of Adrenocorticotropic Hormone on Children With Frequent Relapse or Steroid-dependent Nephrotic Syndrome: a Prospective, Multicenter, Randomized，Open-label Clinical Trial.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 140
- 试验地点
- 8
- 主要终点
- Recurrence-free survival time(day) within 48 weeks
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 useful for primary nephrotic syndrome, proving 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, multicenter, randomized，open-label clinical trial, evaluating the efficacy and safety of steroid combined with adrenocorticotrophic hormone（ACTH） 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 will bring some serious irreversible side effects.
The clinical application of ACTH in children with nephrotic syndrome dates back to the late 1940s. In recent years, the new mechanism of action of ACTH is also being explored. A number of clinical studies on the treatment of nephrotic syndrome by ACTH have found that it can still achieve good efficacy in patients who are ineffective in first-line treatment. This study evaluated the efficacy of ACTH in the treatment of relapsing or steroid-dependent nephrotic syndrome in children, 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 14 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 2-14 years old;
- •Sensitive but frequent relapses or steroids dependence nephrotic syndrome
- •No severe hormonal side effects and/or low-dose steroids dependent idiopathic nephrotic syndrome in children (defined as two relapses with an average dose < 0.5mg/kg/day or equivalent alternate-day dose)
- •Normal renal function: eGFR≥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;
- •Prednisone dose was 1.5-2 mg/kg per day before admission;
- •No use of other immunosuppressants (such as tacrolimus, mortecophenolate, cyclosporin A, cyclophosphamide, levamisole, imidazole ribin, or tripterygium, etc.) within 3 months, and no use of rituximab or beliumab within 6 months.
排除标准
- •Family history of nephrotic syndrome, chronic glomerulonephritis, uremia and other kidney diseases;
- •Patients with congenital or acquired immunodeficiency, or with active tuberculosis, active CMV, EBV, hepatitis B, hepatitis C, HIV infection, deep fungal infection, or other active infections;
- •Recurrent or persistent hypertension;
- •Secondary nephrotic syndrome, such as nephrotic syndrome secondary to systemic lupus erythematosus, diabetes, drug poisoning and infection;
- •Combined with other kidney diseases, such as polycystic kidney, ANCA vasculitis, urinary system malformations, etc.;
- •Patients with hypertension, diabetes, tuberculosis, suppurative or fungal infection, gastric and duodenal ulcer disease and heart failure; Patients with other serious heart, liver and other important organs, blood system, endocrine system and other system lesions;
- •Co-occurrence of other monogenic genetic diseases known to affect the condition of nephrotic syndrome;
- •Patients with serious autoimmune diseases or tumors;
- •Use of other immunosuppressants (such as tacrolimus, mortecophenolate, cyclosporin A, cyclophosphamide, levamisole, imidazole ribin, or tripterygium, etc.) within 3 months, and no use of rituximab or beliumab within 6 months;
- •Patients who are known to be allergic to ACTH, glucocorticoids, or any of the components of these drugs, and patients with severe hormone-related side effects
- •History of organ transplantation (excluding corneal and hair transplantation);
- •Patients who had participated in other clinical trials within three months prior to enrollment;
- •Any patient whom the investigator determines is not suitable for inclusion in the trial.
研究组 & 干预措施
Adrenocorticotrophic Hormone Group
ACTH 2 IU/kg/ day, qd,（the maximum dose ≤ 50 IU）, 28 days of continuous use for 5 days， for 24 weeks.
Prednisone: 5mg；Oral tablets; 1.5-2 mg/kg, qod or 0.75-1mg/kg/day,qd
干预措施: Adrenocorticotrophic Hormone (Drug)
Steroid Group
Prednisone: 5mg；Oral tablets; 1.5-2 mg/kg, qod or 0.75-1mg/kg/day,qd, then gradually taper the steroid by 0.25mg/kg （qod） or 0.125mg/kg （qd） every 4 weeks.
干预措施: Steroid (Drug)
结局指标
主要结局
Recurrence-free survival time(day) within 48 weeks
时间窗: Within 48 weeks after randomization
Recurrence-free survival time(day) within 48 weeks
次要结局
- Number of relapses during 48 weeks follow up(Within 48 weeks after randomization)
- Cumulative prednisone dosage (milligrams per kilogram per year)(Within 48 weeks after randomization)
- Change in serum cholesterol, hemoglobin and blood albumin of the patients(Within 48 weeks after randomization)
- Adverse event(Within 48 weeks after randomization)
- The first time to relapse(Within 48 weeks after randomization)
- Change in anthropometry and growth velocity during 48 weeks after randomization(Within 48 weeks after randomization)
- Change in renal function of the patients(Within 48 weeks after randomization)
- Incidence of infection(Within 48 weeks after randomization)
研究者
Mao Jianhua
professor
The Children's Hospital of Zhejiang University School of Medicine