The study will be a randomized, open-label trial in children with the initial episode of SSNS and whose state of complete remission after received standard prednisolone, to determine whether rituximab (a single intravenous infusion of 375 mg/m2) would be noninferior to corticosteroid alone in maintaining complete disease remission during 12-month of follow-up.
The 12-month relapse-free survival rate is less than 30% in steroid-sensitive nephrotic syndrome (SSNS) children after the standard corticosteroid therapy, with approximately half becoming frequent relapsers or steroid dependent and necessitating the need for alternative immunosuppressive agents. The first relapse of SSNS most occurs within 6-12 months of onset, and contemporary cohorts suggest up to 16-42% of children with SSNS continue to have relapses in adulthood. Rituximab and rituximab biosimilar appear effective in reducing the relapse in children with frequent relapse or steroid dependent nephrotic syndrome. Accordingly, we hypothesize in paediatric SSNS, rituximab added to guideline-recommended corticosteroid therapy is noninferior to corticosteroid alone for maintaining remission for the first year of onset, expected to improve long-term outcomes. An open-label, single-arm, multicentre trial was performed at eight centers in China with a 12-month follow-up (NCT04783675). The study found that in children with the initial episode of SSNS, rituximab appears to be an effective and safe treatment for maintaining disease remission. The goal of this prospective study is to determine whether rituximab (a single intravenous infusion of 375 mg/m2) would be noninferior to corticosteroid alone in maintaining complete disease remission during 12-month of follow-up. The study will be a randomized, open-label, parallel group, in a 1:1 ratio, active controlled, multicenter trial.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
138
Rituximab 375 mg/m2 added to guideline-recommended corticosteroid therapy
guideline-recommended corticosteroid therapy
Children's hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, China
Shanghai's Children's Medical Center
Shanghai, Shanghai Municipality, China
Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, China
1-year relapse-free survival rate
The rate of no relapse within 1 year. Relapse definition: recurrence of nephrotic-range proteinuria, urine protein/creatinine ratio ≥2 mg/mg or dipstick ≥3+ on 3 consecutive days in the first morning samples.
Time frame: 1-year after randomization
Time to relapse (days)
Number of days from randomization to occurrence of first relapse. Relapse definition: recurrence of nephrotic-range proteinuria, urine protein/creatinine ratio ≥2 mg/mg or dipstick ≥3+ on 3 consecutive days in the first morning samples.
Time frame: 1-year after randomization
Peripheral blood T cell subsets
It is a repeat measured variable. Using fluorescence-activated cell sorting, peripheral blood T cells subsets will be studied as percentages and absolute counts.
Time frame: At basline, 1,3,6,9,12 months after randomization
Peripheral blood B cell subsets
It is a repeat measured variable. Using fluorescence-activated cell sorting, peripheral blood B cells subsets will be studied as percentages and absolute counts.
Time frame: At basline, 1,3,6,9,12 months after randomization
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
It is a binary variable (1/0). The variable would be setted as "1" if any adverse events occurs including infusion- related reactions, infection (upper respiratory tract infection, hepatitis B virus reactivation, herpes zoster infection, pneumocystis pneumonia, etc), persistent hypogammaglobulinaemia, encephalopathy, severe neutropenia, fatal pulmonary fibrosis, ulcerative colitis, Crohn's disease and fulminant myocarditis etc. Adverse events will be graded according to the Common Terminology Criteria for Adverse Events
Time frame: 1-year after randomization
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