Enteric-coated Mycophenolate Sodium plus hydroxychloroquine therApy versus hydroxychloroquine for the Remission of Proteinuria in IgA Nephropathy (EMSAR-IgAN trial): study protocol for a randomised trial.

Introduction: The management of immunoglobulin A (IgA) nephropathy remains a topic of debate. Hydroxychloroquine and mycophenolate mofetil (MMF) are two immunosuppressive agents that have recently garnered increased attention among patients with IgA nephropathy in China. Several studies have shown the comparable efficacy between MMF and enteric-coated mycophenolate sodium (EC-MPS), with lower adverse event rates for EC-MPS. The present study aims to evaluate the efficacy and safety of EC-MPS combined with hydroxychloroquine as an immunosuppressive regimen for patients with high-risk progressive IgA nephropathy, despite receiving routine supportive treatment.

Methods And Analysis: This study is a multicentre, prospective, randomised controlled, open-label, blinded endpoint trial. 96 patients diagnosed with IgA nephropathy and persistent proteinuria from 12 general hospitals in Shanxi Province of China will be recruited and randomly assigned to receive either EC-MPS plus hydroxychloroquine or hydroxychloroquine alone in a 1:1 ratio. We will compare the efficacy and safety of hydroxychloroquine combined with or without oral EC-MPS (720-1080 mg/day for 6 months, and tapered to 360-540 mg/day for another 6 months) on a background of supportive care. All enrolled patients will receive standard basic treatment to achieve optimum blood pressure and the maximum tolerated dose of ACE inhibitors or angiotensin receptor blockers. The primary outcome is the change in 24-hour urine protein at 6 months relative to baseline. Participants will be subject to regular follow-up for a duration of 12 months.

Ethics And Dissemination: This study has received ethical approval from the Ethics Committee of Shanxi Medical University Second Hospital (No. 2024YX-481). A duly signed and dated informed consent form must be obtained from each participant or his/her legal guardian prior to any operational procedures related to the trial. The result of this study will be presented and published at international conferences and in scientific journals.

Trial Registration Number: ChiCTR2400093530.