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

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.

Study Overview

• Status: Recruiting
• Conditions: Nephrotic Syndrome
• Intervention / Treatment: Drug: Tacrolimus; Drug: Rituximab

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • West Bengal
    • Kolkata, West Bengal, India, 700014
      • Recruiting
      • NRS Medical College & Hospital
      • Contact: Biswanath Basu; Phone Number: 1804 009123456731; Email: basuv3000@gmail.com
      • Principal Investigator: Biswanath Basu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Nilratan Sircar Medical College
• Investigators: Principal Investigator: Biswanath Basu, Assistant professor

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2015
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: March 3, 2015
• First Submitted That Met QC Criteria: March 5, 2015
• First Posted (Estimate): March 6, 2015

Study Record Updates

• Last Update Posted (Actual): April 7, 2022
• Last Update Submitted That Met QC Criteria: April 6, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Syndrome; Nephrotic Syndrome; Nephrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab; Tacrolimus; Calcineurin Inhibitors
• Other Study ID Numbers: PednephroRCT/PM/NRSMCH-33; CTRI/2015/01/005364 (Registry Identifier: Clinical Trial Registry of India)