Nephrol Dial Transplant. 2017 Dec 1;32(12):2043-2051. doi: 10.1093/ndt/gfw321.
Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis.
UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor-neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients ≥18 years of age with an estimated glomerular filtration rate (eGFR) of ≥45 but <60 mL/min/1.73 m2 and urine albumin:creatinine ratio (uACR) >20 mg/mmol or eGFR ≥20 but <45 mL/min/1.73 m2 (regardless of uACR) were invited to be screened. Following a 4- to 7-week pre-randomization single-blind placebo run-in phase (during which any current renin-angiotensin system inhibitors were stopped), willing and eligible participants were randomly assigned either sacubitril/valsartan or irbesartan and followed-up for 12 months. The primary aim was to compare the effects of sacubitril/valsartan and irbesartan on measured GFR after 12 months of therapy. Important secondary outcomes include effects on albuminuria, change in eGFR over time and the safety and tolerability of sacubitril/valsartan in CKD.
Between November 2014 and January 2016, 620 patients attended a screening visit and 566 (91%) entered the pre-randomization run-in phase. Of these, 414 (73%) participants were randomized (mean age 63 years; 72% male). The mean eGFR was 34.0 mL/min/1.73 m2 and the median uACR was 58.5 mg/mmol.
UK HARP-III will provide important information on the short-term effects of sacubitril/valsartan on renal function, tolerability and safety among patients with CKD.
慢性肾脏病（CKD）患者有进展为终末期肾病和心血管疾病的风险。其他人群的数据和动物实验表明，内肽酶抑制（增强利钠肽系统）可能降低这些风险，但需要在 CKD 患者中进行临床试验来验证这一假设。
英国心脏和肾脏保护 III 期（HARP-III）是一项多中心、双盲、随机对照试验，比较了 sacubitril/valsartan 97/103mg 每日两次（血管紧张素受体-内肽酶抑制剂）与厄贝沙坦 300mg 每日一次在 414 例 CKD 患者中的疗效。年龄≥18 岁、估算肾小球滤过率（eGFR）≥45 但<60mL/min/1.73m2 和尿白蛋白/肌酐比值（uACR）>20mg/mmol 或 eGFR≥20 但<45mL/min/1.73m2（无论 uACR 如何）的患者被邀请参加筛选。在为期 4-7 周的预随机单盲安慰剂导入期（在此期间停用任何当前的肾素-血管紧张素系统抑制剂）后，愿意并符合条件的参与者被随机分配接受 sacubitril/valsartan 或厄贝沙坦治疗，并随访 12 个月。主要目的是比较 sacubitril/valsartan 和厄贝沙坦在 12 个月治疗后对估计肾小球滤过率的影响。重要的次要结局包括对白蛋白尿的影响、随时间推移 eGFR 的变化以及 CKD 中 sacubitril/valsartan 的安全性和耐受性。
2014 年 11 月至 2016 年 1 月，620 例患者参加了筛选访视，566 例（91%）进入预随机导入期。其中，414 例（73%）参与者被随机分组（平均年龄 63 岁；72%为男性）。平均 eGFR 为 34.0mL/min/1.73m2，中位数 uACR 为 58.5mg/mmol。
英国 HARP-III 将提供关于 sacubitril/valsartan 在 CKD 患者中短期对肾功能、耐受性和安全性的重要信息。
