Treatment effects of Chinese Medicine (Yi-Qi-Qing-Jie Herbal Compound) combined With immunosuppression therapies in patients of IgA Nephropathy with high-risk of ESRD (TCM-WINE): study protocol for a randomized controlled trial

Background: IgA nephropathy (IgAN) is the most common glomerular disease worldwide. It has a high incidence in Asians and is more likely to progress to end-stage renal disease (ESRD). However, for high-risk IgAN clinically characterized by massive proteinuria and renal dysfunction, there has been no international consensus on treatment options. Compared with other developed countries, Chinese IgAN patients are often found to have severe kidney function loss at the initial diagnosis. Yi-Qi-Qing-Jie Formula Granule (a compound recipe of Chinese medicinal herbs, YQF) has shown potential renal protection in our previous clinical studies. To further confirm the efficacy and safety of YQF in the treatment of high-risk IgAN, we design a prospective double-blind randomized placebo-controlled trial. Methods/Design: The TCM-WINE study is a single-center, prospective, double-blind placebo-randomized controlled trial. We plan to randomize 60 participants with biopsy-proven IgAN to YQF combined group (YQF compound, combined with prednisolone, and cyclophosphamide if necessary) and immunosuppression group (placebo-YQF, combined with prednisolone, and cyclophosphamide if necessary). The two groups will enter 48-week in-trial treatment phase and receive post-trial follow-up till study completion (3-year). All patients will receive optimal supportive care. The primary composite outcome is defined as the first occurrence of a 40% decrease in estimated glomerular filtration rate (eGFR) from the baseline lasting for 3 months, initiating continuous renal replacement treatment or death due to chronic kidney disease (CKD), during the 3-year study phase. Secondary endpoint events are defined as the mean annual eGFR decline rate (eGFR-Slope, ml/min per 1.73 m 2 per year) which is calculated by the eGFR regression curve for each eligible patient, and proteinuria remission (prescribed as proteinuria<0.5g/day) at week 24, 36, 48 during the in-trial phase. Safety monitoring and assessment will be undertaken during the study . Discussion: TCM-WINE study will evaluate effects and safety of YQF combined therapy compared with immunosuppression monotherapy on basis of optimal supportive treatment in high-risk IgAN. The evidence from this study will provide a novel, effective and safe Chinese characteristics therapy for high-risk IgAN patients. Trial registration: Clinicaltrials.gov, identifier: NCT03418779. Registered on 18 June 2018. https://clinicaltrials.gov/show/NCT03418779