Clinical trial NCT05772871: The Efficacy and Safety of Prednisone Combined With Huaiqihuang Granule for Primary Nephrotic Syndrome in Children
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Nephrotic Syndrome in Children
Keywords: Huaiqihuang granule
Children
Nephrotic syndrome
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
Collaborators: name: LinkDoc Technology (Beijing) Co. Ltd.
First posted: 2023-03-16
Enrollment: 402
Sex: ALL
Minimum age (years): 18
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Maintaining remission rate
timeFrame: Start of randomization until 6-month follow-up
Secondary outcomes:
measure: Remission time to first relapse
timeFrame: Start of onset of remission after treatment until first relapse, assessed up to 6-month
measure: Number of relapses
timeFrame: Start of randomization until 6-month follow-up
measure: Relapse rate
timeFrame: Start of randomization until 6-month follow-up
measure: Incidence of frequently relapse
timeFrame: Start of randomization until 6-month follow-up
measure: Infection rate
timeFrame: Start of medication until 6-month follow-up
measure: Cumulative corticosteroids dosage adjusted by body weight
timeFrame: Start of receiving corticosteroids until 6-month follow-up
measure: Change in serum creatinine and estimated glomerular filtration rate (eGFR) before and after treatment
timeFrame: Start of randomization until 6-month follow-up
measure: Change in serum albumin before and after treatment
timeFrame: Start of randomization until 6-month follow-up
measure: Change in urinary albumin/creatinine ratio (ACR) before and after treatment
timeFrame: Start of randomization until 6-month follow-up
measure: Change in 24h urinary protein (applying to more than 3 years patients) before and after treatment
timeFrame: Start of randomization until 6-month follow-up
measure: Incidence and severity of adverse events (AE) and serious adverse events (SAE)
timeFrame: Start of randomization until 6-month follow-up
measure: Incidence and severity of adverse reactions (ADR), serious adverse reactions (SADR), suspicious and unexpected serious adverse reactions (SUSAR)
timeFrame: Start of randomization until 6-month follow-up
Other outcomes:
measure: Change in blood pressure before and after treatment
timeFrame: Start of randomization until 6-month follow-up
measure: Change in height before and after treatment
timeFrame: Start of randomization until 6-month follow-up
measure: Change in body weight before and after treatment
timeFrame: Start of randomization until 6-month follow-up
measure: Change in BMI before and after treatment
timeFrame: Start of randomization until 6-month follow-up
measure: Change in serum cholesterol before and after treatment
timeFrame: Start of randomization until 6-month follow-up
measure: Change in serum triglycerides before and after treatment
timeFrame: Start of randomization until 6-month follow-up
measure: Change in serum immunoglobulin before and after treatment
timeFrame: Start of randomization until 6-month follow-up
measure: Change in cortisolv (collecting at 8 am) before and after treatment
timeFrame: Start of randomization until 6-month follow-up
measure: Change in serum 25-hydroxyvitamin D before and after treatment
timeFrame: Start of randomization until 6-month follow-up
measure: Change in T cell subtypes before and after treatment
timeFrame: Start of randomization until 6-month follow-up
measure: Change in the nephronectin before and after treatment
timeFrame: Start of randomization until 6-month follow-up
measure: Change in the caveolin-1 before and after treatment
timeFrame: Start of randomization until 6-month follow-up
measure: Change in the heparanase before and after treatment
timeFrame: Start of randomization until 6-month follow-up
measure: The mutation ratio of single nucleotide polymorphism (SNP) in children and their parents at enrollment.
timeFrame: At enrollment until randomization.
Locations:
city: Hefei
country: China
facility: Anhui Children's Hospital
state: Anhui
city: Chongqing
country: China
facility: Children's Hospital of Chongqing Medical University
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Children's Hospital
state: Fujian
city: Fuzhou
country: China
facility: People's Liberation Army Joint Logistics Force No. 900 Hospital
state: Fujian
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Shijiazhuang
country: China
facility: Hebei Children's Hospital
state: Hebei
city: Harbin
country: China
facility: Harbin Children's Hospital
state: Heilongjiang
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical University
state: Henan
city: Zhengzhou
country: China
facility: Henan Children's Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Children's Hospital
state: Hunan
city: Suzhou
country: China
facility: Children's Hospital of Soochow University
state: Jiangsu
city: Changchun
country: China
facility: Baiqiu'en First Hospital of Jilin University
state: Jilin
city: Dalian
country: China
facility: Dalian Women and Children's Medical Centre
state: Liaoning
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Children's Hospital
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Children's Hospital
state: Shanxi
city: Chengde
country: China
facility: West China Second Hospital of Sichuan University
state: Sichuan
city: Chengdu
country: China
facility: Chengdu Women's and Children's Central Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Children's Hospital
state: Tianjin
city: Ürümqi
country: China
facility: Xinjiang Uiger Municipal People's Hospital
state: Xinjiang
city: Hangzhou
country: China
facility: Children's Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo Women's and Children's Hospital
state: Zhejiang
Study officials:
affiliation: Tongji Hospital
name: Jianhua Zhou, Dr.
role: PRINCIPAL_INVESTIGATOR
References: