Randomised controlled trial comparing rituximab to mycophenolate mofetil in children and young adults with steroid-dependent idiopathic nephrotic syndrome: study protocol

Francesca Lugani, Andrea Angeletti, Pietro Ravani, Marina Vivarelli, Manuela Colucci, Gianluca Caridi, Enrico Verrina, Francesco Emma, Gian Marco Ghiggeri, Francesca Lugani, Andrea Angeletti, Pietro Ravani, Marina Vivarelli, Manuela Colucci, Gianluca Caridi, Enrico Verrina, Francesco Emma, Gian Marco Ghiggeri

Abstract

Introduction: Glucocorticoids induce remission in 90% of children with idiopathic nephrotic syndrome (INS). Some become steroid-dependent (SD) and require the addition of steroid sparing drugs such as calcineurin-inhibitors (CNI) or cyclophosphamide, to maintain remission. Considering the toxicity of these drugs, alternative interventions are needed for long-term treatment. The anti-CD20 antibody rituximab has shown promising steroid-sparing properties, with conflicting results in complicated forms of SD-INS. Mycophenolate mofetil (MMF) resulted effective in maintaining free-steroid remission, however, studies are limited to few uncontrolled trials with reported different dose of MMF.

Methods and analysis: This open-label, two-parallel-arm, superiority controlled randomised clinical trial will enrol children with SD-INS maintained in remission with oral glucocorticoids or CNI. Children and young adults will be randomised to either MMF (1.200 mg/m2) or rituximab (375 mg/m2) infusion. After enrolment, glucocorticoids will be tapered until complete withdrawal. We will enrol 160 children and young adults to detect as significant at the two-sided p value of 0.01 with a power >0.8 a reduction in the risk of 1-year relapse (primary end-point). As secondary endpoints, we will compare the amount of glucocorticoids required to maintain complete remission at 6 and 24 months.

Ethics and dissemination: The trial was approved by the local ethics boards (Comitato Etico Regione Liguria CER Liguria https://www.portalericerca-liguria.it/). We will publish the study results at international scientific meetings.

Trial registration numbers: NCT004585152.

Trial registration: ClinicalTrials.gov NCT04585152.

Keywords: clinical pharmacology; clinical trials; glomerulonephritis; immunology; nephrology; paediatric nephrology.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Schematic view of trial design. CNI, calcineurin inhibitors; ITT, intention to treat; MMF, mycophenolate mofetil.

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