Laboratory on Molecular Nephrology, Division of Nephrology, Dialysis, Transplantation, Istituto Giannina Gaslini Istituto di Ricovero e Cura a Carattere Scientifico, Genova, Italy.
Division of Nephrology, Dialysis and Transplantation, Istituto Giannina Gaslini Istituto Pediatrico di Ricovero e Cura a Carattere Scientifico, Genova, Italy.
BMJ Open. 2021 Nov 29;11(11):e052450. doi: 10.1136/bmjopen-2021-052450.
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.
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/m) or rituximab (375 mg/m) 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.
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.
NCT004585152.
糖皮质激素可诱导 90%的特发性肾病综合征（INS）患儿缓解。部分患儿成为激素依赖型（SD），需要添加激素保留药物，如钙调磷酸酶抑制剂（CNI）或环磷酰胺，以维持缓解。鉴于这些药物的毒性，需要寻找其他替代干预措施进行长期治疗。抗 CD20 抗体利妥昔单抗显示出有希望的激素保留特性，但在复杂形式的 SD-INS 中结果存在矛盾。霉酚酸酯（MMF）在维持无激素缓解方面是有效的，但研究仅限于少数非对照试验，且报告的 MMF 剂量不同。
这是一项开放标签、两平行臂、优效性对照随机临床试验，将招募 SD-INS 患儿，这些患儿在用口服糖皮质激素或 CNI 维持缓解。患儿和青少年将被随机分配至 MMF（1200mg/m2）或利妥昔单抗（375mg/m2）输注组。入组后，将逐渐减少糖皮质激素剂量直至完全停药。我们将招募 160 名患儿和青少年，以双侧 p 值 0.01 检测出有统计学意义，效力>0.8，降低 1 年复发风险（主要终点）。次要终点是比较维持 6 个月和 24 个月完全缓解所需的糖皮质激素量。
该试验已获得当地伦理委员会的批准（Comitato Etico Regione Liguria CER Liguria https://www.portalericerca-liguria.it/）。我们将在国际科学会议上公布研究结果。
NCT004585152。
