PDF(Pubmed)
Abstract：
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) leads to progressive renal cyst formation and loss of kidney function in most patients. Vasopressin 2 receptor antagonists (V2RA) like tolvaptan are currently the only available renoprotective agents for rapidly progressive ADPKD. However, aquaretic side effects substantially limit their tolerability and therapeutic potential. In a preliminary clinical study, the addition of hydrochlorothiazide (HCT) to tolvaptan decreased 24-h urinary volume and appeared to increase renoprotective efficacy. The HYDRO-PROTECT study will investigate the long-term effect of co-treatment with HCT on tolvaptan efficacy (rate of kidney function decline) and tolerability (aquaresis and quality of life) in patients with ADPKD.
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.
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.
摘要：
背景：常染色体显性多囊肾病（ADPKD）导致大多数患者进行性肾囊肿形成和肾功能丧失。血管加压素2受体拮抗剂（V2RA），例如托伐普坦，是目前唯一可用于快速进行性ADPKD的肾脏保护剂。然而,水副作用极大地限制了它们的耐受性和治疗潜力。在一项初步的临床研究中,托伐普坦加用氢氯噻嗪(HCT)可减少24小时尿量,并可增加肾脏保护功效.HYDRO-PROTECT研究将研究与HCT共同治疗对ADPKD患者托伐普坦疗效（肾功能下降率）和耐受性（水瘫和生活质量）的长期影响。
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。
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。
