The Efficacy and Safety of Prednisone Combined With Huaiqihuang Granule for Primary Nephrotic Syndrome in Children
- Conditions
- Nephrotic Syndrome in Children
- Interventions
- Drug: Huaiqihuang Granule placebo
- Registration Number
- NCT05772871
- Lead Sponsor
- Jianhua Zhou
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 402
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Prednisone, Huaiqihuang granule, and Levamisole placebo Levamisole placebo In this group, patients will take Prednisone, Huaiqihuang granule, and Levamisole placebo. Prednisone, Levamisole, and Huaiqihuang granule placebo Huaiqihuang Granule placebo In this group, patients will take Prednisone, Levamisole, and Huaiqihuang granule placebo. Prednisone, Huaiqihuang granule, and Levamisole placebo Huaiqihuang granule In this group, patients will take Prednisone, Huaiqihuang granule, and Levamisole placebo. Prednisone, Huaiqihuang granule, and Levamisole placebo Prednisone In this group, patients will take Prednisone, Huaiqihuang granule, and Levamisole placebo. Prednisone, Levamisole, and Huaiqihuang granule placebo Prednisone In this group, patients will take Prednisone, Levamisole, and Huaiqihuang granule placebo. Prednisone, Levamisole, and Huaiqihuang granule placebo Levamisole In this group, patients will take Prednisone, Levamisole, and Huaiqihuang granule placebo.
- Primary Outcome Measures
Name Time Method Maintaining remission rate 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).
- Secondary Outcome Measures
Name Time Method Change in serum albumin before and after treatment Start of randomization until 6-month follow-up The level change of serum albumin between baseline and the last testing result during follow-up
Remission time to first relapse Start of onset of remission after treatment until first relapse, assessed up to 6-month Among patients who get remission after treatment, time from the onset of remission to the first relapse
Relapse rate Start of randomization until 6-month follow-up Among patients who get remission after treatment, proportion of patients with relapse
Incidence of frequently relapse Start of randomization until 6-month follow-up Among patients who get remission after treatment, proportion of patients with more than two times of relapses within 6-month follow-up
Number of relapses Start of randomization until 6-month follow-up Among patients who get remission after treatment, number of relapse per patient
Cumulative corticosteroids dosage adjusted by body weight Start of receiving corticosteroids until 6-month follow-up Total amount of per patient per kilogram cumulative corticosteroids dosage
Change in serum creatinine and estimated glomerular filtration rate (eGFR) before and after treatment Start of randomization until 6-month follow-up The level change of serum creatinine, eGFR between baseline and the last testing result during follow-up
Change in urinary albumin/creatinine ratio (ACR) before and after treatment Start of randomization until 6-month follow-up The level change of urinary albumin/creatinine ratio (ACR) between baseline and the last testing result during 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 Proportion of patients experiencing infection during the treatment. Infections include respiratory tract infections, urinary tract infections, skin infections, gastrointestinal infections, and others.
Change in 24h urinary protein (applying to more than 3 years patients) before and after treatment Start of randomization until 6-month follow-up The level change of 24h urinary protein (applying to more than 3 years patients) between baseline and the last testing result during 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
Trial Locations
- Locations (26)
Children's Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Anhui Children's Hospital
🇨🇳Hefei, Anhui, China
Children's Hospital of Chongqing Medical University
🇨🇳Chongqing, Chongqing, China
Fujian Children's Hospital
🇨🇳Fuzhou, Fujian, China
People's Liberation Army Joint Logistics Force No. 900 Hospital
🇨🇳Fuzhou, Fujian, China
The First Affiliated Hospital, Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
Hebei Children's Hospital
🇨🇳Shijiazhuang, Hebei, China
Harbin Children's Hospital
🇨🇳Harbin, Heilongjiang, China
The First Affiliated Hospital of Xinxiang Medical University
🇨🇳Xinxiang, Henan, China
Henan Children's Hospital
🇨🇳Zhengzhou, Henan, China
The First Affliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Hunan Children's Hospital
🇨🇳Changsha, Hunan, China
Children's Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
Baiqiu'en First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Dalian Women and Children's Medical Centre
🇨🇳Dalian, Liaoning, China
Shandong Provincial Hospital
🇨🇳Jinan, Shandong, China
Shengjing Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Shanxi Children's Hospital
🇨🇳Taiyuan, Shanxi, China
West China Second Hospital of Sichuan University
🇨🇳Chengde, Sichuan, China
Chengdu Women's and Children's Central Hospital
🇨🇳Chengdu, Sichuan, China
Shanghai Children's Hospital
🇨🇳Shanghai, Shanghai, China
Tianjin Children's Hospital
🇨🇳Tianjin, Tianjin, China
Xinjiang Uiger Municipal People's Hospital
🇨🇳Ürümqi, Xinjiang, China
Ningbo Women's and Children's Hospital
🇨🇳Ningbo, Zhejiang, China