Study protocol: multicenter double-blind, randomized, placebo-controlled trial of rituximab for the treatment of childhood-onset early-stage uncomplicated frequently relapsing or steroid-dependent nephrotic syndrome (JSKDC10 trial).


Journal

BMC nephrology
ISSN: 1471-2369
Titre abrégé: BMC Nephrol
Pays: England
ID NLM: 100967793

Informations de publication

Date de publication:
02 08 2019
Historique:
received: 17 11 2018
accepted: 19 07 2019
entrez: 4 8 2019
pubmed: 4 8 2019
medline: 28 10 2020
Statut: epublish

Résumé

Eighty percent of children with idiopathic nephrotic syndrome respond well to steroid therapy, but up to 50% of patients with steroid-sensitive nephrotic syndrome exhibit frequently relapsing (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Several studies identified the chimeric anti-CD20 monoclonal antibody rituximab as an effective treatment for patients with complicated FRNS/SDNS. Recent studies suggested that rituximab could also be a first-line treatment for early-stage uncomplicated FRNS/SDNS, although further studies are required to confirm its efficacy and safety. We are conducting a multicenter, double-blind, randomized placebo controlled trial to investigate the efficacy and safety of rituximab for the treatment of childhood-onset early-stage uncomplicated FRNS/SDNS. Patients will be allocated to receive two 375 mg/m The results will provide important data on the use of rituximab for patients with uncomplicated FRNS/SDNS. In the future, rituximab treatment will enable most patients with uncomplicated FRNS/SDNS to discontinue or reduce steroid therapy without relapse, and it is possible that rituximab could represent an immunosuppressive therapy for these diseases. This trial was prospectively registered to the JMACCT Clinical Trials Registry on September 6, 2018 (Trial ID: JMA-IIA00380 ).

Sections du résumé

BACKGROUND
Eighty percent of children with idiopathic nephrotic syndrome respond well to steroid therapy, but up to 50% of patients with steroid-sensitive nephrotic syndrome exhibit frequently relapsing (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Several studies identified the chimeric anti-CD20 monoclonal antibody rituximab as an effective treatment for patients with complicated FRNS/SDNS. Recent studies suggested that rituximab could also be a first-line treatment for early-stage uncomplicated FRNS/SDNS, although further studies are required to confirm its efficacy and safety.
METHODS/DESIGN
We are conducting a multicenter, double-blind, randomized placebo controlled trial to investigate the efficacy and safety of rituximab for the treatment of childhood-onset early-stage uncomplicated FRNS/SDNS. Patients will be allocated to receive two 375 mg/m
DISCUSSION
The results will provide important data on the use of rituximab for patients with uncomplicated FRNS/SDNS. In the future, rituximab treatment will enable most patients with uncomplicated FRNS/SDNS to discontinue or reduce steroid therapy without relapse, and it is possible that rituximab could represent an immunosuppressive therapy for these diseases.
TRIAL REGISTRATION
This trial was prospectively registered to the JMACCT Clinical Trials Registry on September 6, 2018 (Trial ID: JMA-IIA00380 ).

Identifiants

pubmed: 31375087
doi: 10.1186/s12882-019-1470-3
pii: 10.1186/s12882-019-1470-3
pmc: PMC6679488
doi:

Substances chimiques

Immunologic Factors 0
Placebos 0
Steroids 0
Rituximab 4F4X42SYQ6

Types de publication

Clinical Trial Protocol Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

293

Références

Pediatr Nephrol. 2001 Dec;16(12):1040-4
pubmed: 11793096
Clin J Am Soc Nephrol. 2009 Oct;4(10):1593-600
pubmed: 19808243
Clin J Am Soc Nephrol. 2011 Jun;6(6):1308-15
pubmed: 21566104
Lancet. 2014 Oct 4;384(9950):1273-81
pubmed: 24965823
J Am Soc Nephrol. 2015 Sep;26(9):2259-66
pubmed: 25592855
Cochrane Database Syst Rev. 2015 Mar 18;(3):CD001533
pubmed: 25785660
Clin J Am Soc Nephrol. 2016 Apr 7;11(4):710-20
pubmed: 26585985
Clin Exp Nephrol. 2017 Aug;21(4):651-657
pubmed: 27590892
Pediatr Nephrol. 2017 Nov;32(11):2071-2078
pubmed: 28664242
JAMA Pediatr. 2018 Aug 1;172(8):757-764
pubmed: 29913001

Auteurs

China Nagano (C)

Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.

Mayumi Sako (M)

Division for Clinical Trials, Department of Clinical Research Promotion, Clinical Research Center, National Center for Child Health and Development, Tokyo, Japan.

Koichi Kamei (K)

Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan.

Kenji Ishikura (K)

Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan.

Hidefumi Nakamura (H)

Clinical Research Center, National Center for Child Health and Development, Tokyo, Japan.

Koichi Nakanishi (K)

Department of Child Health and Welfare (Pediatrics), Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

Takashi Omori (T)

Clinical and Translational Research Center, Kobe University Hospital, Kobe, Japan.

Kandai Nozu (K)

Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.

Kazumoto Iijima (K)

Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan. iijima@med.kobe-u.ac.jp.

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Classifications MeSH