Nephrotic SyndromePhase 3NCT02438982
Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Dependent Nephrotic Syndrome
A Phase 3 study testing Tacrolimus and Rituximab in people with Nephrotic Syndrome, run by Nilratan Sircar Medical College at 1 site in India.
Trial 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… Read more about this study
- Who is it for?
- Ages 3 to 16 years
- Conditions the study is for
- Nephrotic Syndrome
- What is being tested?
- Tacrolimus and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteIndia
- Study dates
- 8 May 2015to Sep 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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 (trace or nil proteinuria, as determined by the dipstick test or <100 mg/dl for at least 3 days).
- Not received any steroid sparing agent previously.
- Parents willing to give informed written consent.
- Ability to swallow tablet
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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 SDNS. 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 course 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, the investigators want to compare the efficacy and safety of CNI to that of Rituximab in treating children with SDNS.
- Conditions
- Nephrotic Syndrome
- Being tested
- Tacrolimus, Rituximab
- Medical subject headings
- Nephrotic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TacrolimusDrug
Also called Calcineurin inhibitor
Oral Tacrolimus (Tablet form) 0.2mg/kg/day starting dose. Targeting trough level of Tacrolimus (T0) 5-7 ng/ml.
RituximabDrug
Also called anti CD20 monoclonal antibody
Two rituximab infusions will be administered once every week at standard dose (Intravenous infusion of rituximab 375mg/mt2). Circulating B cells will be measured 24 hours after rituximab administration. If >5 B cells per mm3, it will be measured again after 1 week. If count is still >5 B cells per mm3, third \& fourth doses of rituximab will be given.
| Study group | Role | What they receive |
|---|---|---|
| Tacrolimus | Active comparator | Oral Tacrolimus (Tablet form) 0.2mg/kg/day starting dose. Targeting trough level of Tacrolimus (T0) 5-7 ng/ml. Receives: Drug: Tacrolimus |
| Rituximab | Experimental | Two rituximab infusions will be administered once every week at standard dose (Intravenous infusion of rituximab 375mg/mt2). Circulating B cells will be measured 24 hours after rituximab administration. If >5 B cells per mm3 , it will be measured again after 1 week. If count is still >5 B cells per mm3, third \& fourth doses of rituximab will be given. Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
12-month relapse-free survival
Measured: 12-month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2015 (estimated)
- Study start8 May 2015
- Primary completionAug 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Nephrotic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nilratan Sircar Medical College
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Dr. Biswanath Basu, Nilratan Sircar Medical College
- Investigators
- Biswanath Basu, Principal investigator, Assistant Professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02438982
- Sponsor's protocol ID
- pednephro RCT/PM/NRSMCH-54
- Other IDs
- CTRI/2014/01/004355
- Status last verified
- Jul 2017
- First submitted
- 6 May 2015
- Last updated
- 1 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Larkins NG, Hahn D, Liu ID, Willis NS, Craig JC, Hodson EM. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2024 Nov 8;11(11):CD002290. doi: 10.1002/14651858.CD002290.pub6.
PubMed 39513526Basu B, Sander A, Roy B, Preussler S, Barua S, Mahapatra TKS, Schaefer F. Efficacy of Rituximab vs Tacrolimus in Pediatric Corticosteroid-Dependent Nephrotic Syndrome: A Randomized Clinical Trial. JAMA Pediatr. 2018 Aug 1;172(8):757-764. doi: 10.1001/jamapediatrics.2018.1323.
PubMed 29913001
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Dependent Nephrotic Syndrome
- ClinicalTrials.gov ID
- NCT02438982
- Acronym / sponsor ID
- pednephro RCT/PM/NRSMCH-54
- Conditions
- Nephrotic Syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Nilratan Sircar Medical CollegeOther government
- Study start
- 8 May 2015 (actual)
- Primary completion
- Aug 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 8 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 SDNS. 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 course 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, the investigators want to compare the efficacy and safety of CNI to that of Rituximab in treating children with SDNS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tacrolimus | Active comparator | Drug: TacrolimusOral Tacrolimus (Tablet form) 0.2mg/kg/day starting dose. Targeting trough level of Tacrolimus (T0) 5-7 ng/ml. |
| Rituximab | Experimental | Drug: RituximabTwo rituximab infusions will be administered once every week at standard dose (Intravenous infusion of rituximab 375mg/mt2). Circulating B cells will be measured 24 hours after rituximab administration. If >5 B cells per mm3 , it will be measured again after 1 week. If count is still >5 B cells per mm3, third \& fourth doses of rituximab will be given. |
Who may qualify
- Ages
- 3 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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 (trace or nil proteinuria, as determined by the dipstick test or <100 mg/dl for at least 3 days).
- Not received any steroid sparing agent previously.
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TacrolimusAlso: Calcineurin inhibitorOral Tacrolimus (Tablet form) 0.2mg/kg/day starting dose. Targeting trough level of Tacrolimus (T0) 5-7 ng/ml. | Drug | Tacrolimus |
| RituximabAlso: anti CD20 monoclonal antibodyTwo rituximab infusions will be administered once every week at standard dose (Intravenous infusion of rituximab 375mg/mt2). Circulating B cells will be measured 24 hours after rituximab administration. If >5 B cells per mm3, it will be measured again after 1 week. If count is still >5 B cells per mm3, third \& fourth doses of rituximab will be given. | Drug | Rituximab |
Primary outcome
12-month relapse-free survival
Time frame: 12-month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2017.
- Derived from this study: PubMed 39513526Larkins NG, Hahn D, Liu ID, Willis NS, Craig JC, Hodson EM. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2024 Nov 8;11(11):CD002290. doi: 10.1002/14651858.CD002290.pub6.
- Derived from this study: PubMed 29913001Basu B, Sander A, Roy B, Preussler S, Barua S, Mahapatra TKS, Schaefer F. Efficacy of Rituximab vs Tacrolimus in Pediatric Corticosteroid-Dependent Nephrotic Syndrome: A Randomized Clinical Trial. JAMA Pediatr. 2018 Aug 1;172(8):757-764. doi: 10.1001/jamapediatrics.2018.1323.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Biswanath Basu principal investigator
Assistant Professor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tacrolimus and Rituximab in people with Nephrotic Syndrome, run by Nilratan Sircar Medical College at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
12-month relapse-free survival (time frame: 12-month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02438982, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2017.