- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03899103
Compare Efficacy and Safety of Repeated Courses of Rituximab to That of Maintenance Mycophenolate Mofetil Following Single Course of Rituximab Among Children With Steroid Dependent Nephrotic Syndrome (RITURNS II)
Randomized Clinical Trial to Compare Efficacy and Safety of Repeated Courses of Rituximab to That of Maintenance Mycophenolate Mofetil Following Single Course of Rituximab in Maintaining Remission Over 24 Months Among Children With Steroid Dependent Nephrotic Syndrome
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The vast majority of children with idiopathic nephrotic syndrome respond well to corticosteroid treatment. However, as many as 70% experience at least one relapse, and 30% develop a more complicated course with frequent relapses (FRNS) with or without steroid dependency (SDNS). Extended steroid exposure in these children often results in long-term complications. The management of patients with SDNS is challenging and expensive. Relapses may lead to serious complications, e.g. related to anasarca, hypertension, life threatening infections (peritonitis, pneumonia, meningitis), thrombosis and malnutrition. Repeated courses or even continuous steroid treatment lead to considerable medication related toxicity and morbidity.
The goal of treatment is to reduce the rate of relapses, the cumulative dose of corticosteroids, and the incidence of serious complications. 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 infusion have been shown to be efficacious for 6 to 12 months and the side effect profile observed to date is very benign but after 6-8 months there was relapse due to regeneration of B-lymphocytes, hence for maintenance of remission MMF has been considered. In spite of good initial response, rituximab responders always remain prone to further relapse with regeneration of B lymphocytes, necessitating either repeat course of rituximab or addition of another steroid-sparing immunosuppressant. Reports suggest efficacy of rituximab may vary depending on disease pathology, clinical course, and simultaneous use of other immunosuppressants.
The aim of the RITURNS II study is to evaluate the efficacy and safety of Repeat courses of Rituximab to that of maintenance Mycophenolate Mofetil following single course of Rituximab in maintaining remission over 24 months among Children with Steroid Dependent Nephrotic Syndrome (SDNS).
Study Type
Enrollment (Anticipated)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
West Bengal
-
Kolkata, West Bengal, India, 700014
- Nilratan Sircar Medical College and Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 (Urine albumin nil or trace (or proteinuria <4 mg/m2/h) for 3 consecutive early morning specimens).
- Not received any steroid sparing agent previously.
- Parents willing to give informed written and audiovisual 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 leukopenia (leukocytes <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 one month prior to screening.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Repeated Courses of Rituximab Only
First course Course Rituximab at Randomization.
Prophylactic 2nd and 3rd course rituximab re-administration will be done at 8 months and 16 months of follow-up if B cell count normalize.
|
First course Course Rituximab at Randomization.
|
ACTIVE_COMPARATOR: Rituximab and Mycophenolate Mofetil
First course Course Rituximab at Randomization.
Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards.
|
First course Course Rituximab at Randomization.
Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The primary endpoint is the time to first relapse or death (whichever occurs first) till end of study (follow-up phase of 24 months)
Time Frame: 24 months
|
24 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Cumulative prednisolone requirement (mg/kg/yr) over the first 12 and 24 months, respectively.
Time Frame: 12 and 24 months
|
12 and 24 months
|
Number and severity of adverse events
Time Frame: 0-24 months
|
0-24 months
|
Number of relapses within months 0-24, 0-12 and 12-24, respectively
Time Frame: months 0-24, 0-12 and 12-24
|
months 0-24, 0-12 and 12-24
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
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
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antitubercular Agents
- Antibiotics, Antitubercular
- Rituximab
- Mycophenolic Acid
Other Study ID Numbers
- PednephroRCT/NMC/586
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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