Efficacy and Safety of Mizoribine in comparison with Cyclophosphamide for Treatment of Refractory Nephrotic Syndrome: Protocol for a Multi-center, Controlled, Open-label, Randomized Controlled Trial.

Abstract

Nephrotic syndrome that is resistant to steroidal therapy is termed refractory nephrotic syndrome (RNS), a condition that is associated with an increased risk of end-stage renal disease (ESRD). Immunosuppressants are utilized to treat RNS, however prolonged may lead to significant adverse effects. Mizoribine (MZR) is a novel agent used in long-term immunosuppressive therapy that has few adverse effects, but data on its long-term use in patients with RNS are unavailable. We propose a trial to examine the efficacy and safety of MZR compared to cyclophosphamide (CYC) in Chinese adult patients with RNS. This is a multi-center, randomized, controlled interventional study with a screening phase (1 week) and a treatment phase (52 weeks). This study was reviewed and approved by the Medical Ethics Committees of all 34 medical centers. Patients with RNS consented to participation, and were enrolled and randomized into an MZR group or a CYC group (1:1 ratio), with each group receiving tapering doses of oral corticosteroids. Participants were assessed for adverse effects and collection of laboratory results at 8 visits during the treatment phase on week-4, week-8, week-12, week-16, week-20, week-32, week-44, and week-52 (exit visit). Participants were able to withdraw voluntarily and investigators were required to remove patients when there were safety concerns or deviations from protocol. The study started in November 2014, and was completed in March 2019. A total of 239 participants from 34 hospitals in China were enrolled. Data analysis is completed. The results are waiting to be finalized by Center for Drug Evaluation. The purpose of the current study is to evaluate the efficacy and safety of MZR in comparison with CYC for treatment of RNS in Chinese adult patients with glomerular diseases. It is the longest lasting and largest randomized controlled trial to examine MZR in Chinese patients. The results can help determine whether RNS should be considered as an additional indication for MZR treatment in China. ClinicalTrials.gov Register, NCT02257697. Registered 2014-10-01, https://clinicaltrials.gov/ct2/show/NCT02257697?term=MZR&rank=2.