Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
The George Institute for Global Health, Sydney, Australia.
Nephrol Dial Transplant. 2022 Jul 26;37(8):1461-1471. doi: 10.1093/ndt/gfab237.
Verinurad is a human uric acid (UA) transporter (URAT1) inhibitor known to decrease serum UA (sUA) levels and that may reduce albuminuria. In a Phase 2a study (NCT03118739), treatment with verinurad + febuxostat lowered urine albumin-to-creatinine ratio (UACR) at 12 weeks by 39% (90% confidence interval 4-62%) among patients with Type 2 diabetes mellitus, hyperuricaemia and albuminuria. The Phase 2b, randomized, placebo-controlled Study of verinurAd and alloPurinol in Patients with cHronic kIdney disease and hyperuRicaEmia (SAPPHIRE; NCT03990363) will examine the effect of verinurad + allopurinol on albuminuria and estimated glomerular filtration rate (eGFR) slope among patients with chronic kidney disease (CKD) and hyperuricaemia.
Adults (≥18 years of age) with CKD, eGFR ≥25 mL/min/1.73 m2, UACR 30-5000 mg/g and sUA ≥6.0 mg/dL will be enrolled. Approximately 725 patients will be randomized 1:1:1:1:1 to 12, 7.5 or 3 mg verinurad + allopurinol, allopurinol or placebo. An 8-week dose-titration period will precede a 12-month treatment period; verinurad dose will be increased to 24 mg at Month 9 in a subset of patients in the 3 mg verinurad + allopurinol arm. The primary efficacy endpoint the is change from baseline in UACR at 6 months. Secondary efficacy endpoints include changes in UACR, eGFR and sUA from baseline at 6 and 12 months.
This study will assess the combined clinical effect of verinurad + allopurinol on kidney function in patients with CKD, hyperuricaemia and albuminuria, and whether this combination confers renoprotection beyond standard-of-care.
维那鲁肽是一种人尿酸（UA）转运体（URAT1）抑制剂，已知可降低血清 UA（sUA）水平，并可能减少蛋白尿。在一项 2a 期研究（NCT03118739）中，维那鲁肽+非布司他治疗可使 2 型糖尿病、高尿酸血症和蛋白尿患者的尿白蛋白与肌酐比值（UACR）在 12 周时降低 39%（90%置信区间为 4-62%）。2b 期、随机、安慰剂对照的维那鲁肽和别嘌醇治疗慢性肾脏病和高尿酸血症患者的研究（SAPPHIRE；NCT03990363）将研究维那鲁肽+别嘌醇对慢性肾脏病（CKD）和高尿酸血症患者蛋白尿和估算肾小球滤过率（eGFR）斜率的影响。
年龄≥18 岁的 CKD 患者，eGFR≥25 mL/min/1.73 m2，UACR 30-5000 mg/g 和 sUA≥6.0 mg/dL 将被纳入研究。大约 725 名患者将以 1:1:1:1:1 的比例随机分为维那鲁肽 12、7.5 或 3 mg+别嘌醇、别嘌醇或安慰剂组。在 12 个月的治疗期之前，将进行为期 8 周的剂量滴定期；在 3 mg 维那鲁肽+别嘌醇组的一部分患者中，维那鲁肽剂量将在第 9 个月增加至 24 mg。主要疗效终点是 6 个月时 UACR 自基线的变化。次要疗效终点包括 6 个月和 12 个月时 UACR、eGFR 和 sUA 自基线的变化。
这项研究将评估维那鲁肽+别嘌醇联合治疗 CKD、高尿酸血症和蛋白尿患者的肾脏功能的综合临床效果，以及这种联合治疗是否能提供超越标准治疗的肾脏保护作用。
Zotero 插件
