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

Phase 3
Completed
Conditions
Nephrotic Syndrome
Interventions
Registration Number
NCT02438982
Lead Sponsor
Nilratan Sircar Medical College
Brief Summary

Nephrotic syndrome in children is primarily caused by minimal change disease. Majority of these patients respond well to corticosteroids. However, as many as 70% of children with nephrotic syndrome experience at least one relapse, and 30% develop a more complicated course with frequent relapses (FRNS)(≥2 relapses/ 6 months) with or without steroid dependency (SDNS)(relapse during tapering or within 2 weeks after discontinuation of corticosteroids). Repeated and prolonged courses of steroids in these children often result in long-term complications. The goal of the 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 SDNS. 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.Single rituximab course 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 our proposed randomized controlled trial, the investigators want to compare the efficacy and safety of CNI to that of Rituximab in treating children with SDNS.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
120
Inclusion Criteria
  • Children between 3 and 16 years with SDNS
  • Minimal Change disease/FSGS/MesPGN/ as per Kidney Biopsy report.
  • Estimated glomerular filtration rate (eGFR) >80 ml/min per 1.73 m2 at study entry.
  • Remission at study entry (trace or nil proteinuria, as determined by the dipstick test or <100 mg/dl for at least 3 days).
  • 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
TacrolimusTacrolimusOral Tacrolimus (Tablet form) 0.2mg/kg/day starting dose. Targeting trough level of Tacrolimus (T0) 5-7 ng/ml.
RituximabRituximabTwo rituximab infusions will be administered once every week at standard dose (Intravenous infusion of rituximab 375mg/mt2). Circulating B cells will be measured 24 hours after rituximab administration. If \>5 B cells per mm3 , it will be measured again after 1 week. If count is still \>5 B cells per mm3, third \& fourth doses of rituximab will be given.
Primary Outcome Measures
NameTimeMethod
12-month relapse-free survival12-month
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

NRS Medical College & Hospital

🇮🇳

Kolkata, West Bengal, India

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