Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Resistant Nephrotic Syndrome

Study Overview
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Brief Summary
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The vast majority of children with idiopathic nephrotic syndrome respond well to corticosteroid treatment. However, as many as 20% experience a more complicated course with steroid resistance (SRNS). Repeated and prolonged courses of steroids in these children often result in long-term complications. The goal of treatment is to reduce the rate of relapses, the cumulative dose of corticosteroids, and the incidence of serious complications. In order to minimize the side effects of steroid therapy, different steroid sparing agents such as cyclophosphamide, calcineurin inhibitors(CNI), levamisole, and mycophenolate mofetil (MMF) have been used in SRNS. Whereas CNI are usually considered the steroid sparing drug class of first choice, rituximab is increasingly used as alternative to minimize CNI toxicity. Various prospective studies suggest that Rituximab, a B cell depleting monoclonal antibody, could be a safe and effective alternative to steroid or immunosuppressants to achieve and maintain remission in this population. Rituximab infusion have been shown to be efficacious for 6 to 12 months and the side effect profile observed to date is very benign. Studies comparing the usefulness of these agents are lacking. In this proposed randomized controlled trial, the investigators want to compare the efficacy and safety of CNI to that of Rituximab in treating children with SRNS.

Official Title
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Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Resistant Nephrotic Syndrome

Conditions
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Nephrotic Syndrome

Intervention / Treatment
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* Drug: Rituximab
* Drug: Tacrolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children between 3 and 16 years with SRNS Minimal Change disease/Messengioproliferative glomerulonephritis/Focal segmental glomerulosclerosis as per Kidney Biopsy report. Estimated glomerular filtration rate (eGFR) >80 ml/min per 1.73 m2 at study entry. Not received any steroid sparing agent previously. Parents willing to give informed written consent. Ability to swallow tablet Exclusion Criteria: Known etiology (e.g., lupus erythematosus, IgA nephropathy, amyloidosis, malignancy, other secondary forms of NS) Patients with severe leucopenia (leucocytes <3.0× 1000 cells/mm3), severe anemia (haemoglobin <8.9 g/dl), thrombocytopenia (platelet <100.0 × 1000 cells/mm3) or deranged liver function tests (AST or ALT to >50 IU/L ) at enrolment. Known active chronic infection (tuberculosis, HIV, hepatitis B or C) Live vaccination within 1 mo

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 16 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tacrolimus<br>Tacrolimus: Standard dose with oral Tacrolimus 0.2 mg/kg/day in two divided doses till 6 month of relapse free survival. | Drug: Tacrolimus<br>* Standard dose with oral Tacrolimus 0.2 mg/kg/day in two divided doses till 6 month of relapse free survival.<br>* Other names: Calcineurin inhibitor;|
| Experimental: Rituximab<br>Two to four rituximab infusions (over 2-4 weeks) will be administered once every week at standard dose (Intravenous infusion of rituximab 375mg/mt2)depending on circulating B cells level. | Drug: Rituximab<br>* Two to four rituximab infusions (over 2-4 weeks) will be administered once every week at standard dose (Intravenous infusion of rituximab 375mg/mt2)depending on circulating B cells level.<br>* Other names: anti CD20 monclonal antibody;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12-month relapse-free survival in the intention-to-treat population |  | 12-month |