In the RITURNS trial we demonstrated a substantial and clinically relevant reduction of relapse rates by primary use of Rituximab as compared to standard CNI therapy during a 12-month observation period, accompanied by a more favourable side effect profile [7]. Mycophenolate mofetil (A) or repeated programs of prophylactic Rituximab only (B). In arm A, mycophenolate mofetil (1200?mg/m2 per day) will be started 3 months after Rituximab administration. In arm B, Rituximab infusions will become given at 0, 8 and 16?weeks if B cell count normalize in the specific time points. Prednisolone will become discontinued in both organizations 2 weeks following 1st course of rituximab. Primary aim is definitely to evaluate the difference in 24-month relapse-free survival. Main secondary endpoints are cumulative prednisolone dose, rate of recurrence of relapses and changes in anthropometry. Circulating B lymphocyte populations will HA15 become analyzed as biomarkers or predictors of rituximab responsiveness and adverse events will become analysed. Discussion The study will provide evidence as to the comparative security and effectiveness of two option steroid-sparing therapeutic options in children suffering from steroid dependent nephrotic syndrome. The two-year study design will address the long-term results acquired with the alternative treatment protocols. Trial sign up This trial was prospectively authorized to the Clinicaltrial.gov (“type”:”clinical-trial”,”attrs”:”text”:”NCT03899103″,”term_id”:”NCT03899103″NCT03899103 dated 02/04/2019; https://clinicaltrials.gov/) and Clinical Tests Registry of India (CTRI/2019/04/018517 dated 09/04/2019). Urine protein creatinine percentage The trial was started on 15th May, 2019 in the Division of Pediatric Nephrology, Division of Pediatrics, NRS Medical College & Hospital, Kolkata, India. By 15th September 2020, 70 individuals have been enrolled in the trial. Characteristics of participants Inclusion criteria: children between 3 and 16?years with SDNS; minimal switch disease/FSGS/MesPGN as per kidney biopsy statement; estimated glomerular filtration rate (eGFR) ?80?ml/min per 1.73?m2 at study access; remission at study access (urine albumin nil or trace (or proteinuria ?4?mg/m2/h or uPCR ?200?mg/g ( ?20?mg/mmol)) for 3 consecutive early morning specimens); not received any steroid sparing agent (including levamisole, calcineurin inhibitors, mycophenolate mofetil, cyclophosphamide, mizoribine, chlorambucil or rituximab) previously; parents willing to give knowledgeable written and audiovisual consent; and ability to swallow tablet. Exclusion criteria: known etiology (e.g., lupus erythematosus, IgA nephropathy, amyloidosis, malignancy, additional secondary forms of NS); individuals 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 checks (AST or ALT to ?50?IU/L) at enrolment; known active chronic illness (tuberculosis, HIV, hepatitis B or C); and live vaccination within one month prior to testing. Processes, interventions and comparisons Participant screening and recruitmentConsecutive instances of SDNS showing at the study centre will become screened for eligibility. A preliminary interview for medical and pharmacological history will become performed in order to verify the eligibility HA15 criteria. All participants undergo kidney biopsies before enrolment in the trial. A study investigator will clarify the project, deliver info sheet. Children fulfilling the inclusion criteria will become recruited. The Pediatric Nephrology Division of NRS Medical College & Hospital, Kolkata is one of the largest dedicated pediatric nephrology solutions at Authorities Sector in India. An average of 140C180 children are seen per week in the nephrotic syndrome outpatient medical center; approx. 20C30% of these are new instances and about 60C80% of fresh instances are SDNS. Interventions Arm a (rituximab and mycophenolate mofetil, control treatment) First Program Rituximab at Randomization: Two infusions will become given intravenously at a 7-day time interval at standard dose (rituximab 375?mg/m2, maximum 500?mg). Circulating B cells will become measured 24?h after second rituximab administration. If B cell count exceeds 5/mm3, it will be measured again after 1?week. If count is still ?5/mm3, one more dose of rituximab will be administered. Co-intervention with Rituximab at Randomization: Prednisolone will become continued at alternate-day doses for 2?weeks (1.5?mg/kg (maximum.40?mg) per 48?h in individuals about daily HVH-5 prednisolone at time of randomization; pre-randomization dose in those already on alternate-day dosing). At 2?weeks, prednisolone will be discontinued. Addition of Maintenance MMF from month 4 onwards: Maintenance oral MMF 1200?mg/mt2 daily in two divided doses will be added from month 4 of follow-up and continued over the remaining study period unless an adverse event happens. Arm B (repeated programs of rituximab only, experimental treatment) First Program Rituximab at Randomization: HA15 Same as Arm A. Co-intervention with Rituximab at Randomization: Same as Arm A. Prophylactic 2nd and 3rd Program Rituximab Re-administration at 8?Weeks and.
