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Randomized Controlled Trial
. 2018 Sep 10;19(1):223.
doi: 10.1186/s12882-018-1033-z.

Study protocol: high-dose mizoribine with prednisolone therapy in short-term relapsing steroid-sensitive nephrotic syndrome to prevent frequent relapse (JSKDC05 trial)

Taketsugu Hama  1 , Koichi Nakanishi  2 , Kenji Ishikura  3 , Shuichi Ito  4 , Hidefumi Nakamura  5 , Mayumi Sako  6 , Mari Saito-Oba  7 , Kandai Nozu  8 , Yuko Shima  1 , Kazumoto Iijima  8 , Norishige Yoshikawa  9 ; Japanese Study Group of Kidney Disease in Children (JSKDC)
Affiliations
Randomized Controlled Trial

Study protocol: high-dose mizoribine with prednisolone therapy in short-term relapsing steroid-sensitive nephrotic syndrome to prevent frequent relapse (JSKDC05 trial)

Taketsugu Hama et al. BMC Nephrol. .

Abstract

Background: Eighty percent of children with steroid-sensitive nephrotic syndrome (SSNS) relapse within 2 years and 40-50% patients show frequently-relapsing nephrotic syndrome (FRNS). Patients showing a relapse within 6 months after initial remission are at high risk of FRNS. Since frequent prednisolone treatment for FRNS induces severe prednisolone side effects, development of a treatment to prevent patients from shifting to FRNS is desirable. Mizoribine is an immunosuppressive drug with fewer side effects than prednisolone. Recent studies reported the efficacy of high-dose mizoribine in children with FRNS.

Methods/design: We conduct a multicenter, open, randomized controlled trial to investigate the efficacy and safety of standard prednisolone plus high-dose mizoribine therapy in children with SSNS showing a relapse within 6 months after an initial remission. Patients are allocated to either standard prednisolone alone treatment group, or standard prednisolone plus high-dose mizoribine group. For the former group, mizoribine is administered at a dose of 10 mg/kg/day once daily and continued for 2 years. The primary endpoint is the duration to frequent relapse.

Discussion: The results provide important data on use of high-dose mizoribine to prevent SSNS patients from shifting to FRNS. Since blood concentrations of mizoribine have not been investigated in detail until now, there is a possibility that mizoribine is underestimated in favor of other immunosuppressive drugs. In future, high-dose mizoribine therapy may lead to prevention of relapse in children at high risk of FRNS, and to decreased total dose of prednisolone.

Trial registration: UMIN000005103 , (Prospectively registered 1st March 2011).

Keywords: Frequently-relapsing nephrotic syndrome; Mizoribine; Steroid-sensitive nephrotic syndrome.

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Conflict of interest statement

Ethics approval and consent to participate

This study is performed in accordance with the Declaration of Helsinki and is approved by the regional research ethics vetting boards (Wakayama Medical University). Before enrollment, patients’ guardians provided written informed consent, and informed assent was obtained from older children.

Consent for publication

Not applicable.

Competing interests

KON received a lecture fee from Asahi Kasei Pharma Corp. KI received grants from Asahi Kasei Pharma Corp. and Pfizer Japan Inc., and a lecture fee from Asahi Kasei Pharma Corp. SI received grants from Asahi Kasei Pharma Corp. and Pfizer Japan Inc., and a lecture fee from Asahi Kasei Pharma Corp, Pfizer Japan Inc. and Shionogi & Co., Ltd. HN is a stockholder of Asahi Kasei Pharma Corp. KAN received a lecture fee from Asahi Kasei Pharma Corp. KI has received a grant from Takeda Pharmaceutical Co., Ltd., and lecture fees and/or consulting fees from Asahi Kasei Pharma Corp. and Takeda Pharmaceutical Co., Ltd. The other authors had no disclosure to declare.

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Figures

Fig. 1
Fig. 1
Treatment regimens
See this image and copyright information in PMC

References

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