Compare the Efficacy and Safety of Prednisone Combined With Huaiqihuang Granule Versus Combined With Levamisole for Primary Nephrotic Syndrome in Children: A Prospective, Multi-center, Randomized, Double-blind, Non-inferiority Study
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 402
- 试验地点
- 26
- 主要终点
- Maintaining remission rate
研究概览
简要总结
This non-inferiority study aims to compare the efficacy of Prednisone combined with Huaiqihuang Granule against Prednisone combined with Levamisole in the treatment of primary nephrotic syndrome (PNS) in children.
详细描述
Nephrotic syndrome (NS) is the most frequent glomerular disease in children, with an incidence of 1.15-16.9 per 100,000 children. Children present with the disease at a median age of 2-3 years, and it is twice as common in boys. More than 90% of children who present with NS respond to corticosteroid treatment, and current practice is to treat most patients empirically with prednisone. However, after initial successful treatment, around 80% of children with steroid sensitive NS have disease relapses requiring further courses of prednisone. About 50% of patients develop frequent relapsing or steroid dependent. Further, the long-term use of corticosteroids is associated with numerous side effects, like obesity, diabetes and hypertension.
Traditional Chinese medicine plays a unique role in the enhancement of immune function and kidney function. Huaiqihuang granule is composed of Trametes robiniophila Murr, Fructus Lycii, and Polygonatum sibiricum. It has been used for the treatment of primary nephrotic syndrome (PNS) in China. Previous studies showed Huaiqihuang granule combined with corticosteroids could significantly decrease relapse and infection rates of PNS and were well tolerated by children. This non-inferiority study aims to compare the efficacy of Prednisone combined with Huaiqihuang Granule against Prednisone combined with Levamisole in the treatment of PNS in children.
In this study, about 20 research centers will participate. A total of 402 participants will be divided into two groups (the intervention group and control group) at a ratio of 1:1. The intervention group will receive Prednisone, Huaiqihuang granule and Levamisole placebo, and the control group will receive Prednisone, Levamisole and Huaiqihuang granule placebo. The planned length of patient recruitment enrolment will be 2 years and the total length of visits be 6 months. After enrollment, participants will be followed up until the end of the study (6 months), second relapse, develop as steroid-resistant, lost to follow-up, withdrawal from the study for any reason, or die, whichever occurs first.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age from 1.5 to 18 years;
- •According to the Evidence-based Guideline for Diagnosis and Treatment of Hormone-sensitive, Relapsed/dependent Nephrotic Syndrome in Children (2016), children diagnosed with PNS;
- •At enrollment, estimated glomerular filtration rate (eGFR)≥90ml/min/1.73m2；
- •At enrollment, serum albumin level below 30g/L, and morning urine protein is 4+ or urinary albumin/creatinine ratio (ACR)≥2.0g/g;
- •Volunteered to participate in this study and signed informed consent. For children less than 8 years, legal guardians need to sign the informed consent.
排除标准
- •Children who were diagnosed as steroid-resistant NS;
- •Patients who received Prednisone, other corticosteroids (like Prednisolone, Methylprednisolone), or immunosuppressants (Tacrolimus, Mycophenolate Mofetil, Cyclosporine A, Rituximab, Cyclophosphamide) within 3 months before enrollment;
- •Secondary NS caused by lupus nephritis, hepatitis B associated nephritis, purpura nephritis, and EB virus, cytomegalovirus (CMV), etc;
- •With combined diseases of autoimmune disorder or primary immunodeficiency or malignancy;
- •With combined diseases of the cardiovascular, liver, hematopoietic system, mental disorders, and other serious diseases;
- •With serious infectious diseases (like tuberculosis) in the past or at present;
- •With combined diseases of Human immunodeficiency virus (HIV), hepatitis B and /or C virus (HBV, HCV), and other active virus infections;
- •History of diabetes;
- •Abnormal liver function: alanine aminotransferase and aspartate aminotransferase levels exceed twice the upper limit of the normal range;
- •Participation in other ongoing clinical trials;
- •Other reasons that the researcher considers unsuitable to participate in this study.
研究组 & 干预措施
Prednisone, Huaiqihuang granule, and Levamisole placebo
In this group, patients will take Prednisone, Huaiqihuang granule, and Levamisole placebo.
干预措施: Huaiqihuang granule (Drug)
Prednisone, Huaiqihuang granule, and Levamisole placebo
In this group, patients will take Prednisone, Huaiqihuang granule, and Levamisole placebo.
干预措施: Prednisone (Drug)
Prednisone, Huaiqihuang granule, and Levamisole placebo
In this group, patients will take Prednisone, Huaiqihuang granule, and Levamisole placebo.
干预措施: Levamisole placebo (Drug)
Prednisone, Levamisole, and Huaiqihuang granule placebo
In this group, patients will take Prednisone, Levamisole, and Huaiqihuang granule placebo.
干预措施: Prednisone (Drug)
Prednisone, Levamisole, and Huaiqihuang granule placebo
In this group, patients will take Prednisone, Levamisole, and Huaiqihuang granule placebo.
干预措施: Levamisole (Drug)
Prednisone, Levamisole, and Huaiqihuang granule placebo
In this group, patients will take Prednisone, Levamisole, and Huaiqihuang granule placebo.
干预措施: Huaiqihuang Granule placebo (Drug)
结局指标
主要结局
Maintaining remission rate
时间窗: Start of randomization until 6-month follow-up
At the end of the study, the proportion of patients who maintained urine protein negative without relapse (removed the patients who developed steroid resistance at the first 4 weeks of treatment of Prednisone).
次要结局
- Change in serum albumin before and after treatment(Start of randomization until 6-month follow-up)
- Remission time to first relapse(Start of onset of remission after treatment until first relapse, assessed up to 6-month)
- Relapse rate(Start of randomization until 6-month follow-up)
- Incidence of frequently relapse(Start of randomization until 6-month follow-up)
- Number of relapses(Start of randomization until 6-month follow-up)
- Cumulative corticosteroids dosage adjusted by body weight(Start of receiving corticosteroids until 6-month follow-up)
- Change in serum creatinine and estimated glomerular filtration rate (eGFR) before and after treatment(Start of randomization until 6-month follow-up)
- Change in urinary albumin/creatinine ratio (ACR) before and after treatment(Start of randomization until 6-month follow-up)
- Incidence and severity of adverse events (AE) and serious adverse events (SAE)(Start of randomization until 6-month follow-up)
- Infection rate(Start of medication until 6-month follow-up)
- Change in 24h urinary protein (applying to more than 3 years patients) before and after treatment(Start of randomization until 6-month follow-up)
- Incidence and severity of adverse reactions (ADR), serious adverse reactions (SADR), suspicious and unexpected serious adverse reactions (SUSAR)(Start of randomization until 6-month follow-up)
研究者
Jianhua Zhou
Professor
Tongji Hospital