Efficacy of Repeated courses of Rituximab vs. Rituximab and Mycophenolate Mofetil among Children Nephrotic Syndrome

Phase 3

Recruiting

Conditions: Nephrotic syndrome with minor glomerular abnormality,

Registration Number: CTRI/2019/04/018517

Lead Sponsor: NRS Medical college and Hospital

Brief Summary: The vast majority of children with idiopathicnephrotic syndrome respond well to corticosteroid treatment. However, as manyas 70% experience at least one relapse, and 30% develop a more complicatedcourse with frequent relapses (FRNS) with or without steroid dependency (SDNS).Extended steroid exposure in these children often results in long-termcomplications. The management of patients with SDNS is challenging andexpensive. Relapses may lead to serious complications, e.g. related toanasarca, hypertension, life threatening infections (peritonitis, pneumonia, meningitis),thrombosis and malnutrition. Repeated courses or even continuous steroidtreatment lead to considerable medication related toxicity and morbidity.

The goal of treatment is to reduce the rate ofrelapses, the cumulative dose of corticosteroids, and the incidence of seriouscomplications. Various prospective studies suggest that Rituximab, a B celldepleting monoclonal antibody, could be a safe and effective alternative tosteroid or immunosuppressants to achieve and maintain remission in thispopulation. Single rituximab infusionhave been shown to be efficacious for 6 to 12 months and the side effectprofile observed to date is very benign but after 6-8 months there was relapsedue to regeneration of B-lymphocytes, hence for maintenance of remission MMFhas been considered. In spite of good initial response, rituximab respondersalways remain prone to further relapse with regeneration of B lymphocytes,necessitating either repeat course of rituximab or addition of anothersteroid-sparing immunosuppressant. Reports suggest efficacy of rituximab mayvary depending on disease pathology, clinical course, and simultaneous use ofother immunosuppressants.

The aim of the RITURNSII study is to evaluate the efficacy and safety of Repeat courses of Rituximabto that of maintenance Mycophenolate Mofetil following single course ofRituximab in maintaining remission over 24 months among Children with SteroidDependent Nephrotic Syndrome (SDNS)

Detailed Description: Not available

Recruitment & Eligibility

Status: Open to Recruitment

Sex: All

Target Recruitment: 100

Inclusion Criteria

1.Children between 3 and 16 years with SDNS.
2.Minimal Change disease/ FSGS/MesPGN as per Kidney Biopsy report.
3.Estimated glomerular filtration rate(eGFR) >80 ml/min per 1.73 m2 at study entry.
4.Remission at study entry (Urine albumin nil or trace (or proteinuria <4 mg/m2/h) for 3 consecutive early morning specimens).
5.Not received any steroid sparing agent previously.
6.Parents willing to give informed written and audiovisual consent.
7.Ability to swallow tablet.

Exclusion Criteria

1.Known etiology (e.g., lupus erythematosus, IgA nephropathy, amyloidosis, malig-nancy, other secondary forms of NS).
2.Patients with severe leukopenia (leukocytes <3.0Ã— 1000 cells/mm3), severe anemia (haemoglobin<8.9 g/dl), thrombocytopenia (platelet <100.0 Ã— 1000 cells/mm3) orderanged liver function tests (AST or ALT to >50 IU/L ) at enrolment.
3.Known active chronic infection (tuberculosis, HIV, hepatitis B or C).
4.Live vaccination within one month prior to screening.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary endpoint is the time to first relapse or death (whichever occurs first) till end of study (follow-up phase of 24 months).	The primary endpoint is the time to first relapse or death (whichever occurs first) till end of study (follow-up phase of 24 months).

Secondary Outcome Measures

Name	Time	Method
1.Cumulative prednisolone requirement (mg/kg/yr) over the first 12 and 24 months, respectively.
Number and severity of adverse events	0-24 months
Number of relapses within months 0-24, 0-12 and 12-24, respectively	months 0-24, 0-12 and 12-24

Trial Locations

Locations (1): Nilratan Sircar Medical College and Hospital
🇮🇳
Kolkata, WEST BENGAL, India
Nilratan Sircar Medical College and Hospital
🇮🇳Kolkata, WEST BENGAL, India
Biswanath Basu
Principal investigator
09231236001
basuv3000@gmail.com