Rituximab Trial for Pediatric Nephrotic Syndrome

Study Overview
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Brief Summary
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Anti-CD20 agent has been proposed as a rescue therapy for refractory nephrotic syndrome(NS) on the basis of favorable clinical observations. Yet the long-term effect on maintaining remission or the likelihood of becoming rituximab-dependent is unclear and the information on the safety profile of rituximab is limited. This trial was designed to investigate the safety and efficacy of Rituximab in children with refractory NS.

Official Title
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A Multi-center Randomized Controlled Trial of Rituximab for Refractory Nephrotic Syndrome in Children

Conditions
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Steroid Resistant Nephrotic Syndrome, Steroid Dependent Nephrotic Syndrome

Intervention / Treatment
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* Drug: Rituximab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (A)steroid/calcineurin inhibitor resistant nephrotic syndrome steroid resistance: no remission after 4 weeks of daily oral corticosteroid (60mg/m2/day) calcineurin inhibitor resistance: no remission after 3 months of therapeutic dose administration of cyclosporine and/or tacrolimus no remission defined by persistent proteinuria of nephrotic range for the last 3 months post-transplant patients were included in the study (B)steroid-dependent nephrotic syndrome Steroid-dependent patients who had been on various known medications (such as corticosteroids, cyclophosphamide, chlorambucil, calcineurin inhibitors, levamisole ..) continuously for more than 2 years definition of dependency: more than two consecutive relapse events in 2 weeks after discontinuation of steroid or calcineurin inhibitor no improvement in relapsing frequency with calcineurin inhibitor use unable to continue with calcineurin inhibitor due to side effects unable to continue with calcineurin inhibitor due to prolonged use (over 2 years) other conditions in which the clinician considers difficult to control disease with steroids or calcineurin inhibitors only. Exclusion Criteria: previous rituximab use secondary nephrotic syndrome estimated GFR <60mL/min/1.73m2 or under 50% of age-matched standard GFR chronic or acute active infection (e.g. hepatitis B,C, herpes, varicella zoster) prior live vaccine inoculation within 1 month (from the study enrollment) cardiovascular diseases, pulmonary or pleural diseases uncontrolled hypertension leukocytopenia (absolute neutrophil count <1500/mm3) or thrombocytopenia (<75000/mm3) pregnancy

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: steroid-resistant<br>Steroid-resistant group: n=27 , enroll all for treatment | Drug: Rituximab<br>* Per dose: Rituximab 375 mg/m2 (max.500mg/day). efficacy monitored by CD19 cell count. If CD19 cells are not depleted, second or third doses are given at 2-3 weeks interval.<br>* Other names: 2005110300291 (rituximab);|
| Active Comparator: steroid-dependent-rituximab<br>steroid-responsive group: n=38 | Drug: Rituximab<br>* Per dose: Rituximab 375 mg/m2 (max.500mg/day). efficacy monitored by CD19 cell count. If CD19 cells are not depleted, second or third doses are given at 2-3 weeks interval.<br>* Other names: 2005110300291 (rituximab);|
| Placebo Comparator: steroid-dependent-placebo<br>steroid-responsive group: n=23 | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The remission rate of steroid-resistant nephrotic syndrome patients after rituximab treatment |  | within 6 months from the initiation of treatment | 
| The rate of maintaining remission in steroid-dependent nephrotic syndrome patients |  | within 6 months from the initiation of treatment versus placebo control | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rituximab, nephrotic, refractory