Back to resultsEfficacy and Safety of Rituximab Versus Mycophenolate Mofetil in Children With Steroid-dependent Nephrotic Syndrome
Primary Purpose
Nephrotic Syndrome in Children
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Rituximab
Mycophenolate Mofetil
Sponsored by
About this trial
This is an interventional treatment trial for Nephrotic Syndrome in Children focused on measuring Nephrotic Syndrome, Rituximab, Mycophenolate Mofetil
Eligibility Criteria
Inclusion Criteria: Children with a definite diagnosis of SDNS are included in the study during relapse treatment. Age 3-16 years. Steroid dependent dose≤0.3mg/kg/day. Cumulative steroid use for ≥6 months. Ability to swallow tablet. Guardians understand the characteristics and personal consequences of clinical trial. Guardians willing to give informed written consent. Exclusion Criteria: Diagnosis of secondary NS, such as secondary to lupus nephritis, hepatitis B-related nephritis, purpura nephritis, etc. Anti-neutrophil cytoplasmic antibodies(ANCA) positive or complement C3 level decreased. Diagnosis of hereditary nephrotic syndrome. Full dose of prednisone (2mg/kg/day, maximum 60mg) are used for 14 days after relapse and urine protein don't turn negative. Estimated glomerular filtration rate (eGFR) <90mL/min per 1.73m^2 at study entry. Those who with a known allergy to Mycophenolate Mofetil and their excipients or to Rituximab and its excipients. Those who refuse to participate in the trial. Those who participate other clinical trials. Those who with positive HBV serological markers (HBsAg or/and HBeAg or/and HBcAb), HCV positive patients or patients with abnormal liver function (ALT,AST,or bilirubin>2 or more times the upper limit of the normal range and persistently elevated for 2 weeks). Severe leukopenia (white blood cells<3.0×10^9), severe anemia (hemoglobin<90g/l), and thrombocytopenia (platelets<100×10^9) at study entry. History of pancreatitis or definite gastrointestinal ulcers and/or gastrointestinal bleeding within 6 months. Those who with congenital or acquired immune deficiency, or with active tuberculosis, active CMV and other infections. Those who with other serious physical or mental illnesses. History of malignant tumor within 5 years. Those who with congenital heart disease, arrhythmia, heart failure and other serious cardiovascular diseases. Those who with serious infections requiring intravenous antibiotics.
Sites / Locations
- Children's Hospital of Chongqing Medical UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Rituximab
Mycophenolate Mofetil
Arm Description
2 doses of rituximab 375 mg/m^2 (Maximum 500mg/day)at 6 months intervals
MMF 20~30mg/kg/day，BID
Outcomes
Primary Outcome Measures
12-month relapse-free survival rate
The rate of no relapse within 12 months.
Secondary Outcome Measures
6-month relapse-free survival
Relapse-free survival within 6 months.
6-month relapse-free survival rate
The rate of no relapse within 6 months.
12-month relapse-free survival
Relapse-free survival within 12 months.
Proportion of frequent relapses
The proportion of frequent relapses.Frequent relapsing NS:≥2 relapses per 6 months within 6 months of disease onset or ≥4 relapses per 12 months in any subsequent 12-month period.
Cumulative steroid dosage
The total dosage of steroid from the beginning to the end of the trial.
Number of relapses within 0-12,0-6, and 7-12 months
Number of relapses within 0-6 months,7-12 months, and total within 0-12 months.
Time of first relapse
The first time to relapse after patients taking part in this study.
Adverse event
It is a binary variable(1/0).The varibale would be setted as "1" if any adverse events occours including obesity, hypertrichosis, psychological disorders,glaucoma,neutropenia,hypogammaglobulinemia, rituximab-related lung injury, fatal hepatitis reactivation, multifocal leukoencephalopathy,severe diarrhea, severe infection. Adverse events graded according to Common Terminology Criteria For Adverse Events (CTCAE v4.0）
Proportion of participants who discontinued steroids
Proportion of participants who discontinued steroids at 12 months
Height standard deviation score(SDS)
SDS of height at 6 and 12 months, absolute and relative changes in SDS from baseline to 12 months.
Body mass index(BMI)
Weight and height will be combined to report BMI in kg/m^2. BMI at 6 and 12 months, absolute and relative changes in BMI from baseline to 12 months.
Quality of life score
The researchers assess the quality of life of the participants useing Pediatric Quality of Life Inventory (PedsQL).
Cost of treatment
The researchers calculate their cost during the study.
Full Information
NCT ID
NCT05843968
First Posted
April 8, 2023
Last Updated
May 6, 2023
Sponsor
Children's Hospital of Chongqing Medical University
1. Study Identification
Unique Protocol Identification Number
NCT05843968
Brief Title
Efficacy and Safety of Rituximab Versus Mycophenolate Mofetil in Children With Steroid-dependent Nephrotic Syndrome
Official Title
Rituximab Versus Mycophenolate Mofetil in Children With Steriod-dependent Nephrotic Syndrome: A Single-center, Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2023 (Anticipated)
Primary Completion Date
July 1, 2026 (Anticipated)
Study Completion Date
July 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Children's Hospital of Chongqing Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The goal of this clinical trial is to evaluate the efficacy and safety of rituximab(RTX) and mycophenolate mofetile(MMF) in the treatment of children with low-dose steroid-dependent nephrotic syndrome(SDNS).
Detailed Description
Idiopathic nephrotic syndrome（INS） is the most common glomerular disease in childhood. Currently, steroids are the primary treatment, but there are significant steroid-related toxicity, such as growth disorders, behavior changes, obesity, Cushing's syndrome, eye disease, osteoporosis, etc.
Both MMF and RTX have been shown to be effective in the treatment of SDNS, and there is a lack of prospective controlled studies to explore the optimal treatment regimen for low-dose SDNS. Therefore, the investigators will conduct a single-center, randomized controlled trial to evaluate the efficacy and safety of twice-daily rituximab(RTX) versus mycophenolate mofetil(MMF) in the treatment of children with low-dose steroid-dependent nephrotic syndrome(SDNS).
After the start of the study, all participants will be screened consecutively and eligible participants will be included in the study. Bias of potential influencing factors will be addressed by inclusion as covariates in the statistical analysis. Independent clinical site monitoring to ensure the safety and integrity of clinical data while patients adhere to the study protocol will focus on source data documentation, strict adherence to data correctness and study procedures, such as randomization and treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nephrotic Syndrome in Children
Keywords
Nephrotic Syndrome, Rituximab, Mycophenolate Mofetil
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
46 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Rituximab
Arm Type
Experimental
Arm Description
2 doses of rituximab 375 mg/m^2 (Maximum 500mg/day)at 6 months intervals
Arm Title
Mycophenolate Mofetil
Arm Type
Active Comparator
Arm Description
MMF 20~30mg/kg/day，BID
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituximab Injection
Intervention Description
2 doses of rituximab 375 mg/m^2(maximum 500mg/day) at 6 months intervals.
Half an hour before rituximab infusion: oral acetaminophen 15mg/kg, oral or intramuscular antihistamine, methylprednisolone 2mg/kg IV. Trimethoprim-sulfamethoxazole should be administered orally from the initiation of rituximab therapy until peripheral-blood B cell recovery to prevent pneumocystis infection.
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Other Intervention Name(s)
Mycophenolate Mofetil Dispersible tablets
Intervention Description
Mycophenolate Mofetil 20-30 mg/kg/day BID,then adjust the dosage of drugs(maximum 2g/day) to maintian the concentration for MPA-AUC is 30-50μg.h/ml. Total duration:1year.
Steroids dose:1.5mg/kg(maximum 40mg) qod for 2 weeks and gradually taper by 0.3 mg/kg every 2 weeks
Primary Outcome Measure Information:
Title
12-month relapse-free survival rate
Description
The rate of no relapse within 12 months.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
6-month relapse-free survival
Description
Relapse-free survival within 6 months.
Time Frame
6 months
Title
6-month relapse-free survival rate
Description
The rate of no relapse within 6 months.
Time Frame
6 months
Title
12-month relapse-free survival
Description
Relapse-free survival within 12 months.
Time Frame
12 months
Title
Proportion of frequent relapses
Description
The proportion of frequent relapses.Frequent relapsing NS:≥2 relapses per 6 months within 6 months of disease onset or ≥4 relapses per 12 months in any subsequent 12-month period.
Time Frame
Months 6,12
Title
Cumulative steroid dosage
Description
The total dosage of steroid from the beginning to the end of the trial.
Time Frame
12 months
Title
Number of relapses within 0-12,0-6, and 7-12 months
Description
Number of relapses within 0-6 months,7-12 months, and total within 0-12 months.
Time Frame
12 months
Title
Time of first relapse
Description
The first time to relapse after patients taking part in this study.
Time Frame
12 months
Title
Adverse event
Description
It is a binary variable(1/0).The varibale would be setted as "1" if any adverse events occours including obesity, hypertrichosis, psychological disorders,glaucoma,neutropenia,hypogammaglobulinemia, rituximab-related lung injury, fatal hepatitis reactivation, multifocal leukoencephalopathy,severe diarrhea, severe infection. Adverse events graded according to Common Terminology Criteria For Adverse Events (CTCAE v4.0）
Time Frame
12 months
Title
Proportion of participants who discontinued steroids
Description
Proportion of participants who discontinued steroids at 12 months
Time Frame
12 months
Title
Height standard deviation score(SDS)
Description
SDS of height at 6 and 12 months, absolute and relative changes in SDS from baseline to 12 months.
Time Frame
months 0,6,12
Title
Body mass index(BMI)
Description
Weight and height will be combined to report BMI in kg/m^2. BMI at 6 and 12 months, absolute and relative changes in BMI from baseline to 12 months.
Time Frame
Months 0,6,12
Title
Quality of life score
Description
The researchers assess the quality of life of the participants useing Pediatric Quality of Life Inventory (PedsQL).
Time Frame
Baseline to 12 months
Title
Cost of treatment
Description
The researchers calculate their cost during the study.
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Children with a definite diagnosis of SDNS are included in the study during relapse treatment.
Age 3-16 years.
Steroid dependent dose≤0.3mg/kg/day.
Cumulative steroid use for ≥6 months.
Ability to swallow tablet.
Guardians understand the characteristics and personal consequences of clinical trial.
Guardians willing to give informed written consent.
Exclusion Criteria:
Diagnosis of secondary NS, such as secondary to lupus nephritis, hepatitis B-related nephritis, purpura nephritis, etc.
Anti-neutrophil cytoplasmic antibodies(ANCA) positive or complement C3 level decreased.
Diagnosis of hereditary nephrotic syndrome.
Full dose of prednisone (2mg/kg/day, maximum 60mg) are used for 14 days after relapse and urine protein don't turn negative.
Estimated glomerular filtration rate (eGFR) <90mL/min per 1.73m^2 at study entry.
Those who with a known allergy to Mycophenolate Mofetil and their excipients or to Rituximab and its excipients.
Those who refuse to participate in the trial.
Those who participate other clinical trials.
Those who with positive HBV serological markers (HBsAg or/and HBeAg or/and HBcAb), HCV positive patients or patients with abnormal liver function (ALT,AST,or bilirubin>2 or more times the upper limit of the normal range and persistently elevated for 2 weeks).
Severe leukopenia (white blood cells<3.0×10^9), severe anemia (hemoglobin<90g/l), and thrombocytopenia (platelets<100×10^9) at study entry.
History of pancreatitis or definite gastrointestinal ulcers and/or gastrointestinal bleeding within 6 months.
Those who with congenital or acquired immune deficiency, or with active tuberculosis, active CMV and other infections.
Those who with other serious physical or mental illnesses.
History of malignant tumor within 5 years.
Those who with congenital heart disease, arrhythmia, heart failure and other serious cardiovascular diseases.
Those who with serious infections requiring intravenous antibiotics.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yang Haiping, Doctor
Phone
8618983703661
Email
oyhp@hospital.cqmu.edu.cn
Facility Information:
Facility Name
Children's Hospital of Chongqing Medical University
City
Chongqing
State/Province
Chongqing
ZIP/Postal Code
400014
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Li Qiu, Doctor
Phone
8613708353809
Email
liqiu809@hospital.cqmu.edu.cn
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Safety of Rituximab Versus Mycophenolate Mofetil in Children With Steroid-dependent Nephrotic Syndrome
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