The Efficacy and Safety of Prednisone Combined With Huaiqihuang Granule for Primary Nephrotic Syndrome in Children

Nephrotic Syndrome in Children Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05772871
• Other study ID #: HQH-202205
• Status: Recruiting
• Phase: Phase 4
• Start date: April 26, 2023
• Est. completion date: October 30, 2025

Study information

• Verified date: December 2023
• Source: Tongji Hospital
• Contact: Jianhua Zhou, Dr.
• Phone: 86+13367266559
• Email: jhzhou[@]tjh.tjmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 402
• Est. completion date: October 30, 2025
• Est. primary completion date: September 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Months to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Nephrosis
• Nephrotic Syndrome
• Nephrotic Syndrome in Children
• Syndrome

Intervention

Drug:
• Huaiqihuang granule
Huaiqihuang Granule, oral administration, recommended daily dose: for body weight <10 kg, 5g, twice a day; for 10 kg = body weight <20 kg, 10g, twice a day; for 20 kg=body weight <30 kg, 15g, twice a day; for 30 kg=body weight <50 kg, 20g, twice a day; for body weight>50 kg, 30g, twice a day. Continuous medication until the end of the study (6 months), second relapse, development as steroid-resistant, lost to follow-up, withdrawal from the study for any reason, or death, whichever occurs first.
• Prednisone
Prednisone, oral administration, recommended dose: 2mg/kg/d (maximum 60 mg/d) for 4 weeks followed by 2 mg/kg (maximum 60mg) on alternate days for the other 4 weeks. If patients have relapsed during reducing dosage or withdrawal, the patients will receive Prednisone for 8 weeks again [2mg/kg/d (maximum 60 mg/d) for 4 weeks followed by 2 mg/kg (maximum 60mg) on alternate days for the other 4 weeks]. If a second relapse is observed, patients will receive immunosuppressants and then withdraw from the trial.
• Levamisole placebo
Levamisole placebo, 1.25 mg/kg. once daily. Continuous medication until the end of the study (6 months), second relapse, development as steroid-resistant, lost to follow-up, withdrawal from the study for any reason, or death, whichever occurs first.
• Levamisole
Levamisole, 1.25 mg/kg. once daily. Continuous medication until the end of the study (6 months), second relapse, development as steroid-resistant, lost to follow-up, withdrawal from the study for any reason, or death, whichever occurs first.
• Huaiqihuang Granule placebo
Huaiqihuang Granule placebo, oral administration, recommended daily dose: for body weight <10 kg, 5g, twice a day; for 10 kg = body weight <20 kg, 10g, twice a day; for 20 kg=body weight <30 kg, 15g, twice a day; for 30 kg=body weight <50 kg, 20g, twice a day; for body weight>50 kg, 30g, twice a day. Continuous medication until the end of the study (6 months), second relapse, development as steroid-resistant, lost to follow-up, withdrawal from the study for any reason, or death, whichever occurs first.

Locations

Country	Name	City	State
China	Hunan Children's Hospital	Changsha	Hunan
China	Chengdu Women's and Children's Central Hospital	Chengdu	Sichuan
China	Fujian Children's Hospital	Fuzhou	Fujian
China	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	Xinjiang Uiger Municipal People's Hospital	Ürümqi	Xinjiang
China	Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
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

Sponsors (2)

Lead Sponsor	Collaborator
Jianhua Zhou	LinkDoc Technology (Beijing) Co. Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in blood pressure before and after treatment	The level change of blood pressure before and after treatment	Start of randomization until 6-month follow-up
Other	Change in height before and after treatment	The level change of height before and after treatment	Start of randomization until 6-month follow-up
Other	Change in body weight before and after treatment	The level change of body weight before and after treatment	Start of randomization until 6-month follow-up
Other	Change in BMI before and after treatment	The level change of BMI before and after treatment	Start of randomization until 6-month follow-up
Other	Change in serum cholesterol before and after treatment	The level change of serum cholesterol before and after treatment	Start of randomization until 6-month follow-up
Other	Change in serum triglycerides before and after treatment	The level change of serum triglycerides before and after treatment	Start of randomization until 6-month follow-up
Other	Change in serum immunoglobulin before and after treatment	The level change of serum immunoglobulin before and after treatment	Start of randomization until 6-month follow-up
Other	Change in cortisolv (collecting at 8 am) before and after treatment	The level change of cortisolv (collecting at 8 am) before and after treatment	Start of randomization until 6-month follow-up
Other	Change in serum 25-hydroxyvitamin D before and after treatment	The level change of serum 25-hydroxyvitamin D before and after treatment	Start of randomization until 6-month follow-up
Other	Change in T cell subtypes before and after treatment	The level change of T cell subtypes before and after treatment	Start of randomization until 6-month follow-up
Other	Change in the nephronectin before and after treatment	The level change of nephronectin before and after treatment	Start of randomization until 6-month follow-up
Other	Change in the caveolin-1 before and after treatment	The level change of caveolin-1 before and after treatment	Start of randomization until 6-month follow-up
Other	Change in the heparanase before and after treatment	The level change of heparanase before and after treatment	Start of randomization until 6-month follow-up
Other	The mutation ratio of single nucleotide polymorphism (SNP) in children and their parents at enrollment.	The testing SNP including rs 2285450, rs 2073901, rs 3129888, rs 4979462 and et al.	At enrollment until randomization.
Primary	Maintaining remission rate	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).	Start of randomization until 6-month follow-up
Secondary	Remission time to first relapse	Among patients who get remission after treatment, time from the onset of remission to the first relapse	Start of onset of remission after treatment until first relapse, assessed up to 6-month
Secondary	Number of relapses	Among patients who get remission after treatment, number of relapse per patient	Start of randomization until 6-month follow-up
Secondary	Relapse rate	Among patients who get remission after treatment, proportion of patients with relapse	Start of randomization until 6-month follow-up
Secondary	Incidence of frequently relapse	Among patients who get remission after treatment, proportion of patients with more than two times of relapses within 6-month follow-up	Start of randomization until 6-month follow-up
Secondary	Infection rate	Proportion of patients experiencing infection during the treatment. Infections include respiratory tract infections, urinary tract infections, skin infections, gastrointestinal infections, and others.	Start of medication until 6-month follow-up
Secondary	Cumulative corticosteroids dosage adjusted by body weight	Total amount of per patient per kilogram cumulative corticosteroids dosage	Start of receiving corticosteroids until 6-month follow-up
Secondary	Change in serum creatinine and estimated glomerular filtration rate (eGFR) before and after treatment	The level change of serum creatinine, eGFR between baseline and the last testing result during follow-up	Start of randomization until 6-month follow-up
Secondary	Change in serum albumin before and after treatment	The level change of serum albumin between baseline and the last testing result during follow-up	Start of randomization until 6-month follow-up
Secondary	Change in urinary albumin/creatinine ratio (ACR) before and after treatment	The level change of urinary albumin/creatinine ratio (ACR) between baseline and the last testing result during follow-up	Start of randomization until 6-month follow-up
Secondary	Change in 24h urinary protein (applying to more than 3 years patients) before and after treatment	The level change of 24h urinary protein (applying to more than 3 years patients) between baseline and the last testing result during follow-up	Start of randomization until 6-month follow-up
Secondary	Incidence and severity of adverse events (AE) and serious adverse events (SAE)		Start of randomization until 6-month follow-up
Secondary	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