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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
402
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, 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.
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).
Time frame: Start of randomization until 6-month follow-up
Remission time to first relapse
Among patients who get remission after treatment, time from the onset of remission to the first relapse
Time frame: Start of onset of remission after treatment until first relapse, assessed up to 6-month
Number of relapses
Among patients who get remission after treatment, number of relapse per patient
Time frame: Start of randomization until 6-month follow-up
Relapse rate
Among patients who get remission after treatment, proportion of patients with relapse
Time frame: Start of randomization until 6-month follow-up
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
Time frame: Start of randomization until 6-month follow-up
Infection rate
Proportion of patients experiencing infection during the treatment. Infections include respiratory tract infections, urinary tract infections, skin infections, gastrointestinal infections, and others.
Time frame: Start of medication until 6-month follow-up
Cumulative corticosteroids dosage adjusted by body weight
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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, 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, 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.
Anhui Children's Hospital
Hefei, Anhui, China
RECRUITINGChildren's Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, China
RECRUITINGFujian Children's Hospital
Fuzhou, Fujian, China
RECRUITINGPeople's Liberation Army Joint Logistics Force No. 900 Hospital
Fuzhou, Fujian, China
RECRUITINGThe First Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, China
RECRUITINGHebei Children's Hospital
Shijiazhuang, Hebei, China
RECRUITINGHarbin Children's Hospital
Harbin, Heilongjiang, China
RECRUITINGThe First Affiliated Hospital of Xinxiang Medical University
Xinxiang, Henan, China
RECRUITINGHenan Children's Hospital
Zhengzhou, Henan, China
RECRUITINGThe First Affliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
RECRUITING...and 16 more locations
Total amount of per patient per kilogram cumulative corticosteroids dosage
Time frame: Start of receiving corticosteroids until 6-month follow-up
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
Time frame: Start of randomization until 6-month follow-up
Change in serum albumin before and after treatment
The level change of serum albumin between baseline and the last testing result during follow-up
Time frame: Start of randomization until 6-month follow-up
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
Time frame: Start of randomization until 6-month follow-up
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
Time frame: Start of randomization until 6-month follow-up
Incidence and severity of adverse events (AE) and serious adverse events (SAE)
Time frame: 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)
Time frame: Start of randomization until 6-month follow-up