Daprodustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) being investigated for the treatment of anemia of CKD. In this noninferiority trial, we compared daprodustat administered three times weekly with epoetin alfa (epoetin) in patients on prevalent hemodialysis switching from a prior erythropoiesis-stimulating agent (ESA).

Patients on hemodialysis with a baseline hemoglobin of 8–11.5 g/dl receiving an ESA were randomized 2:1 to daprodustat three times weekly (n=270) or conventional epoetin (n=137) for 52 weeks. Dosing algorithms aimed to maintain hemoglobin between 10 and 11 g/dl. The primary end point was mean change in hemoglobin from baseline to the average during the evaluation period (weeks 28–52). The principal secondary end point was average monthly intravenous iron dose. Other secondary end points included BP and hemoglobin variability.

Daprodustat three times weekly was noninferior to epoetin for mean change in hemoglobin (model-adjusted mean treatment difference [daprodustat-epoetin], –0.05; 95% confidence interval, –0.21 to 0.10). During the evaluation period, mean (SD) hemoglobin values were 10.45 (0.55) and 10.51 (0.85) g/dl for daprodustat and epoetin groups, respectively. Responders (defined as mean hemoglobin during the evaluation period in the analysis range of 10 to 11.5 g/dl) were 80% in the daprodustat group versus 64% in the epoetin group. Proportionately fewer participants in the daprodustat group versus the epoetin group had hemoglobin values either below 10 g/dl or above 11.5 g/dl during the evaluation period. Mean monthly intravenous iron use was not significantly lower with daprodustat versus epoetin. The effect on BP was similar between groups. The percentage of treatment-emergent adverse events was similar between daprodustat (75%) and epoetin (79%).

Daprodustat was noninferior to epoetin in hemoglobin response and was generally well tolerated.

Anemia Studies in Chronic Kidney Disease: Erythropoiesis via a Novel Prolyl Hydroxylase Inhibitor Daprodustat–Three Times Weekly Dosing in Dialysis (ASCEND-TD), NCT03400033

Daprodustat 是一种缺氧诱导因子脯氨酰羟化酶抑制剂 (HIF-PHI)，正在研究用于治疗 CKD 贫血。在这项非劣效性试验中，我们比较了从先前的红细胞生成刺激剂 (ESA) 转而进行血液透析的患者每周服用 3 次的达普司他与阿法依泊汀 (epoetin)。

基线血红蛋白为 8-11.5 g/dl 且接受 ESA 的血液透析患者以 2:1 的比例随机分配至达普司他，每周 3 次 ( n = 270) 或传统促红细胞生成素 ( n = 137)，持续 52 周。剂量算法旨在将血红蛋白维持在 10 至 11 g/dl 之间。主要终点是评估期间（第 28-52 周）血红蛋白从基线到平均值的平均变化。主要次要终点是平均每月静脉铁剂剂量。其他次要终点包括血压和血红蛋白变异性。

就血红蛋白平均变化而言，达普司他每周 3 次并不劣于依泊汀（模型调整平均治疗差值 [达布司他-依泊汀]，–0.05；95% 置信区间，–0.21 至 0.10）。在评估期间，达普司他和依泊汀组的平均 (SD) 血红蛋白值分别为 10.45 (0.55) 和 10.51 (0.85) g/dl。达普司他组的应答者（定义为评估期间的平均血红蛋白在 10 至 11.5 g/dl 的分析范围内）为 80%，而促红细胞生成素组为 64%。在评估期间，与红细胞生成素组相比，达普司他组中血红蛋白值低于 10 g/dl 或高于 11.5 g/dl 的参与者比例要少。与依泊汀相比，达普司他的平均每月静脉铁剂使用量并未显着降低。组间对血压的影响相似。达普司他 (75%) 和依泊汀 (79%) 之间治疗引起的不良事件的百分比相似。

达普司他的血红蛋白反应不劣于促红细胞生成素，并且通常具有良好的耐受性。

慢性肾病贫血研究：通过新型脯氨酰羟化酶抑制剂 Daprodustat 促进红细胞生成——透析中每周三次给药 (ASCEND-TD)，NCT03400033