Steno Diabetes Center, Niels Steensenvej 1, DK-2820 Gentofte, Denmark.
Diabetologia. 2010 Aug;53(8):1576-80. doi: 10.1007/s00125-010-1789-6. Epub 2010 May 18.
The optimal antiproteinuric dose of aliskiren is unknown. This study compared the effect of placebo and increasing doses of aliskiren on urinary albumin excretion rate (UAER).
The trial was a double-blind crossover design. Twenty-six patients with type 2 diabetes mellitus, hypertension and albuminuria were randomised to 2-month treatments with placebo or aliskiren 150 mg, 300 mg or 600 mg once daily, in random order. Primary endpoint was change in UAER; secondary endpoints included changes in 24-h BP, GFR, biomarkers and components of the renin-angiotensin-aldosterone system.
Placebo geometric mean UAER was 350 mg/day, mean 24-h BP was 137/81 (SD 12/9) mmHg, GFR was 85 (SD 26) ml min(-1) 1.73 m(-2). Aliskiren 150, 300 and 600 mg daily reduced UAER significantly by 36% (95% CI 17-51), 48% (33-60) and 52% (38-63) respectively (p < 0.001) compared with placebo. UAER reduction during the 600 mg dose was not significantly different from the 300 mg dose. Twenty-four-hour systolic BP was reduced by 4.5, 8.0 and 9.2 mmHg versus placebo, significant for 300 and 600 mg (p < or = 0.001). Twenty-four-hour diastolic BP was reduced by 3.0, 4.1 and 4.4 mmHg, significant versus placebo (p = 0.019, p = 0.001 and p < 0.001). GFR was reduced by 3.0, 5.1 and 6.5 ml min(-1) 1.73 m(-2). hsPRA was reduced by 63%, 70%, and 82% (p < 0.001 for all). Adverse events, most frequently dizziness and fatigue, occurred during all doses.
In patients with type 2 diabetes mellitus, hypertension and albuminuria there is no improved antiproteinuric effect when using 600 mg aliskiren daily compared with the maximal recommended antihypertensive dose of 300 mg.
Clinicaltrials.gov NCT00464776
Novartis Pharma AG.
阿利克仑的最佳降蛋白剂量尚不清楚。本研究比较了安慰剂和递增剂量阿利克仑对尿白蛋白排泄率（UAER）的影响。
该试验采用双盲交叉设计。26 例 2 型糖尿病、高血压伴蛋白尿患者随机接受为期 2 个月的安慰剂或阿利克仑 150mg、300mg 或 600mg 每日 1 次治疗，随机顺序。主要终点为 UAER 的变化；次要终点包括 24 小时血压、GFR、生物标志物和肾素-血管紧张素-醛固酮系统成分的变化。
安慰剂几何均数 UAER 为 350mg/天，平均 24 小时血压为 137/81（SD 12/9）mmHg，GFR 为 85（SD 26）ml/min·1.73m-2。阿利克仑 150、300 和 600mg/d 分别显著降低 UAER 36%（95%CI 17-51）、48%（33-60）和 52%（38-63）（均 P<0.001），与安慰剂相比。600mg 剂量时的 UAER 降低与 300mg 剂量时无显著差异。与安慰剂相比，24 小时收缩压分别降低 4.5、8.0 和 9.2mmHg，300 和 600mg 时显著（均 P<0.001）。24 小时舒张压分别降低 3.0、4.1 和 4.4mmHg，与安慰剂相比差异有统计学意义（P=0.019、P=0.001 和 P<0.001）。GFR 分别降低 3.0、5.1 和 6.5ml/min·1.73m-2。hsPRA 分别降低 63%、70%和 82%（均 P<0.001）。不良反应，最常见的是头晕和疲劳，发生在所有剂量组。
在 2 型糖尿病、高血压伴蛋白尿患者中，与最大推荐降压剂量 300mg 相比，每日使用 600mg 阿利克仑并无改善的降蛋白作用。
Clinicaltrials.gov NCT00464776
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