CTRI Number |
CTRI/2014/01/004355 [Registered on: 28/01/2014] Trial Registered Prospectively |
Last Modified On: |
19/09/2016 |
Post Graduate Thesis |
No |
Type of Trial |
Interventional |
Type of Study
|
Drug |
Study Design |
Randomized, Parallel Group Trial |
Public Title of Study
|
A study to compare effectiveness for preventing disease recurrence and safety regarding drug related side effects between a newer-safe drug(Rituximab) and conventionally used drug(Calcineurin Inhibitors)in children with difficult to treat nephrotic syndrome, a chronic protein loosing kidney disease. |
Scientific Title of Study
Modification(s)
|
Randomized Clinical Trial to Compare Efficacy and Safety of Rituximab to That of
Calcineurin Inhibitor in Children With Steroid Dependent Nephrotic Syndrome |
Trial Acronym |
RITURNS (rituximab for relapse prevention in nephrotic syndrome) |
Secondary IDs if Any
Modification(s)
|
Secondary ID |
Identifier |
NCT02438982 |
ClinicalTrials.gov |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
Name |
Biswanath Basu |
Designation |
Assistant Professor and In charge, Division of Pediatric Nephrology |
Affiliation |
NRS Medical College and Hospital |
Address |
Dept. of Pediatrics,
NRS Medical College and Hospital,
AJC Bose Road.
Kolkata-14
WEST BENGAL
Kolkata WEST BENGAL 700014 India |
Phone |
913323453245 |
Fax |
|
Email |
basuv3000@gmail.com |
|
Details of Contact Person Scientific Query
|
Name |
Biswanath Basu |
Designation |
Assistant Professor and In charge, Division of Pediatric Nephrology |
Affiliation |
NRS Medical College and Hospital |
Address |
Dept. of Pediatrics,
NRS Medical College and Hospital,
AJC Bose Road.
Kolkata-14
WEST BENGAL
Kolkata WEST BENGAL 700014 India |
Phone |
913323453245 |
Fax |
|
Email |
basuv3000@gmail.com |
|
Details of Contact Person Public Query
|
Name |
Biswanath Basu |
Designation |
Assistant Professor and In charge, Division of Pediatric Nephrology |
Affiliation |
NRS Medical College and Hospital |
Address |
Dept. of Pediatrics,
NRS Medical College and Hospital,
AJC Bose Road.
Kolkata-14
WEST BENGAL
Kolkata WEST BENGAL 700014 India |
Phone |
913323453245 |
Fax |
|
Email |
basuv3000@gmail.com |
|
Source of Monetary or Material Support
|
NRS Medical College and Hospital |
|
Primary Sponsor
|
Name |
NRS Medical College and Hospital |
Address |
AJC Bose Road. Kolkata-14
WEST BENGAL
700014
India |
Type of Sponsor |
Government medical college |
|
Details of Secondary Sponsor
|
Name |
Address |
Self |
NRS Medical College and Hospital |
|
Countries of Recruitment
|
India |
Sites of Study
|
No of Sites = 1 |
Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
Biswanath Basu |
Room No.16, Div. of Pediatric Nephrology and OPD, Dept. of Pediatrics, NRS Medical College |
NRS Medical College and Hospital, 138,AJC Bose Road. Kolkata-14
Kolkata
WEST BENGAL Kolkata WEST BENGAL |
9231236001
basuv3000@gmail.com |
|
Details of Ethics Committee
|
No of Ethics Committees= 1 |
Name of Committee |
Approval Status |
Institute ethics committee, NRS Medical College and Hospital |
Approved |
|
Regulatory Clearance Status from DCGI
|
|
Health Condition / Problems Studied
|
Health Type |
Condition |
Patients |
Nephrotic Syndrome , |
|
Intervention / Comparator Agent
Modification(s)
|
Type |
Name |
Details |
Intervention |
Rituximab |
Two infusions will be administered intravenously at a 7-day interval at standard dose (rituximab 375mg/m2, maximum 500mg). Circulating B cells will be measured 24 hours after rituximab administration. If B cell count exceeds 5/mm3, it will be measured again after 1 week. If count still exceeds 5/mm3, two more doses of rituximab will be administered. |
Comparator Agent |
Tacrolimus |
Oral (Tablet form) 0.2mg/kg/day starting dose and continued over 12 months. Target tacrolimus trough level: 5-7 ng/ml.
|
|
Inclusion Criteria
Modification(s)
|
Age From |
3.00 Year(s) |
Age To |
16.00 Year(s) |
Gender |
Both |
Details |
Children between 3 and 16 years with SDNS
Minimal Change disease/ FSGS/MesPGN as per Kidney Biopsy report.
Estimated glomerular filtration rate(eGFR) more than 80 ml/min per 1.73 m2 at study entry.
Remission at study entry (trace or nil proteinuria, as determined by the dipstick test or less than 100 mg/dl for at least 3 days).
Not received any steroid sparing agent previously.
Parents willing to give informed written and audiovisual consent.
Ability to swallow tablet
|
|
ExclusionCriteria |
Details |
Known etiology (e.g., lupus erythematosus, IgA nephropathy, amyloidosis, malignancy, other secondary forms of NS)
Patients with severe leucopenia (leucocytes less than 3.0× 1000 cells/mm3), severe anemia (haemoglobin less than 8.9 g/dl), thrombocytopenia (platelet less than 100.0 × 1000 cells/mm3) or deranged liver function tests (AST or ALT to more than 50 IU/L ) at enrolment.
Known active chronic infection (tuberculosis, HIV, hepatitis B or C)
|
|
Method of Generating Random Sequence
Modification(s)
|
Stratified block randomization |
Method of Concealment
Modification(s)
|
|
Blinding/Masking
Modification(s)
|
Open Label |
Primary Outcome
Modification(s)
|
Outcome |
TimePoints |
12-month relapse-free survival |
12 |
|
Secondary Outcome
Modification(s)
|
Outcome |
TimePoints |
eGFR at 3, 6, 9 and 12 months, respectively.
Amount of cumulative prednisolone requirement (mg/kg/yr) over 12 months
Number of relapses within months 0-12, 0-6 and 7-12.
Number of different steroid toxicity events (new onset) within month 0-12
Time to first relapse
Fraction of patients off steroids at month 12
Abnormal values in biochemical tests and haematology assessments.
Changes in Height sds and BMI sds from baseline to 12 months.
|
6,12 |
|
Target Sample Size
|
Total Sample Size="60" Sample Size from India="60"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
Phase of Trial
Modification(s)
|
Phase 3 |
Date of First Enrollment (India)
Modification(s)
|
08/05/2015 |
Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
Date of First Enrollment (Global) |
Date Missing |
Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
Estimated Duration of Trial
Modification(s)
|
Years="1" Months="8" Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
Publication Details
|
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
Brief Summary
|
Nephrotic syndrome in children is primarily caused by minimal change disease. Majority of these patients respond well to corticosteroids. However, as many as 70% of children with nephrotic syndrome experience at least one relapse, and 30% develop a more complicated course with frequent relapses (FRNS)(≥2 relapses/ 6 months) with or without steroid dependency (SDNS)(relapse during tapering or within 2 weeks after discontinuation of corticosteroids). Repeated and prolonged courses of steroids in these children often result in long-term complications. The goal of the 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 FRNS. 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.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. Studies comparing the usefulness of these agents are lacking. In our proposed randomized controlled trial, we want to compare the efficacy and safety of CNI to that of Rituximab in treating children with FRNS and SDNS. |