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

Sponsor

Nilratan Sircar Medical College (Other)

Overall Status

Recruiting

CT.gov ID

NCT02382575

Collaborator

(none)

120

Enrollment

Location

Arms

104.6

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Nephrotic Syndrome	Drug: Rituximab Drug: Tacrolimus	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 15, 2015

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Tacrolimus Tacrolimus: Standard dose with oral Tacrolimus 0.2 mg/kg/day in two divided doses till 6 month of relapse free survival.	Drug: Tacrolimus Standard dose with oral Tacrolimus 0.2 mg/kg/day in two divided doses till 6 month of relapse free survival. Other Names: Calcineurin inhibitor
Experimental: Rituximab 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 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. Other Names: anti CD20 monclonal antibody

Arm

Intervention/Treatment

Active Comparator: Tacrolimus

Tacrolimus: Standard dose with oral Tacrolimus 0.2 mg/kg/day in two divided doses till 6 month of relapse free survival.

Drug: Tacrolimus

Standard dose with oral Tacrolimus 0.2 mg/kg/day in two divided doses till 6 month of relapse free survival.

Other Names:

Calcineurin inhibitor

Experimental: Rituximab

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

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.

Other Names:

anti CD20 monclonal antibody

Outcome Measures

Primary Outcome Measures

12-month relapse-free survival in the intention-to-treat population [12-month]

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 16 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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