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

NCT02382575 | Unknown Phase 4 DMC

• 2 other identifiers: PednephroRCT/PM/NRSMCH-33CTRI/2015/01/005364
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Nephrotic Syndrome

Outcome Measures

Primary Outcomes (1)

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

  12-month

Study Arms (2)

Tacrolimus

ACTIVE COMPARATOR

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

Drug: Tacrolimus

Rituximab

EXPERIMENTAL

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

Interventions

Rituximab DRUG

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.

Also known as: anti CD20 monclonal antibody

Rituximab

Tacrolimus DRUG

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

Also known as: Calcineurin inhibitor

Tacrolimus

Eligibility Criteria

• Age: 3 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nilratan Sircar Medical College: lead

Study Sites (1)

NRS Medical College & Hospital

Kolkata, West Bengal, 700014, India

RECRUITING

Related Publications (1)

• Liu ID, Willis NS, Craig JC, Hodson EM. Interventions for idiopathic steroid-resistant nephrotic syndrome in children. Cochrane Database Syst Rev. 2025 May 8;5(5):CD003594. doi: 10.1002/14651858.CD003594.pub7.

  PMID: 40337980 DERIVED

MeSH Terms

Conditions

Nephrotic Syndrome

Interventions

Rituximab; Tacrolimus; Calcineurin Inhibitors

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Organic Chemicals; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Biswanath Basu

  Assistant Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor & In charge, Division of Pediatric Nephrology

Study Record Dates

• First Submitted: March 3, 2015
• First Posted: March 6, 2015
• Study Start: March 15, 2015
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: April 7, 2022

Record last verified: 2022-04

Locations

IN (1)