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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)

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ClinicalTrials.gov Identifier: NCT03899103
Recruitment Status : Recruiting
First Posted : April 2, 2019
Last Update Posted : May 17, 2019
Sponsor:
Collaborator:
Heidelberg University
Information provided by (Responsible Party):
Dr. Biswanath Basu, Nilratan Sircar Medical College

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Steroid-Dependent Nephrotic Syndrome Drug: Rituximab Drug: Mycophenolate Mofetil Phase 3

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).


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 15, 2019
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : October 2021


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.
Drug: Rituximab
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.
Drug: Rituximab
First course Course Rituximab at Randomization.

Drug: Mycophenolate Mofetil
Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Cumulative prednisolone requirement (mg/kg/yr) over the first 12 and 24 months, respectively. [ Time Frame: 12 and 24 months ]
  2. Number and severity of adverse events [ Time Frame: 0-24 months ]
  3. Number of relapses within months 0-24, 0-12 and 12-24, respectively [ Time Frame: months 0-24, 0-12 and 12-24 ]


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Ages Eligible for Study:   3 Years to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03899103


Locations
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India
Nilratan Sircar Medical College and Hospital Recruiting
Kolkata, West Bengal, India, 700014
Contact: BISWANATH BASU, MD    9231236001    basuv3000@gmail.com   
Sponsors and Collaborators
Nilratan Sircar Medical College
Heidelberg University

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Responsible Party: Dr. Biswanath Basu, Associate Professor, Nilratan Sircar Medical College
ClinicalTrials.gov Identifier: NCT03899103     History of Changes
Other Study ID Numbers: PednephroRCT/NMC/586
First Posted: April 2, 2019    Key Record Dates
Last Update Posted: May 17, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Syndrome
Nephrotic Syndrome
Nephrosis
Disease
Pathologic Processes
Kidney Diseases
Urologic Diseases
Rituximab
Mycophenolic Acid
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action