METHODS: The HYDRO-PROTECT study is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized clinical trial. The study is powered to enroll 300 rapidly progressive patients with ADPKD aged ≥ 18 years, with an eGFR of > 25 mL/min/1.73 m2, and on stable treatment with the highest tolerated dose of tolvaptan in routine clinical care. Patients will be randomly assigned (1:1) to daily oral HCT 25 mg or matching placebo treatment for 156 weeks, in addition to standard care.
RESULTS: The primary study outcome is the rate of kidney function decline (expressed as eGFR slope, in mL/min/1.73 m2 per year) in HCT versus placebo-treated patients, calculated by linear mixed model analysis using all available creatinine values from week 12 until the end of treatment. Secondary outcomes include changes in quality-of-life questionnaire scores (TIPS, ADPKD-UIS, EQ-5D-5L, SF-12) and changes in 24-h urine volume.
CONCLUSIONS: The HYDRO-PROTECT study will demonstrate whether co-treatment with HCT can improve the renoprotective efficacy and tolerability of tolvaptan in patients with ADPKD.
方法:HYDRO-PROTECT研究是研究者发起的,多中心,双盲,安慰剂对照,随机临床试验。该研究有能力招募300名年龄≥18岁的ADPKD快速进展患者,eGFR>25mL/min/1.73m2,并且在常规临床护理中使用最高耐受剂量的托伐普坦进行稳定治疗。患者将被随机分配(1:1)每天口服HCT25mg或匹配的安慰剂治疗156周,除了标准护理。
结果:主要研究结果是肾功能下降率(以eGFR斜率表示,以mL/min/1.73m2/年为单位),在HCT与安慰剂治疗的患者中,通过线性混合模型分析计算,使用从12周到治疗结束的所有可用肌酐值。次要结果包括生活质量问卷评分的变化(TIPS,ADPKD-UIS,EQ-5D-5L,SF-12)和24小时尿量的变化。
结论:HYDRO-PROTECT研究将证明与HCT联合治疗是否可以提高托伐普坦对ADPKD患者的肾脏保护功效和耐受性。