University of New South Wales, Sydney, NSW, Australia.
GlaxoSmithKline, Collegeville, PA, USA.
Nephrol Dial Transplant. 2022 Oct 19;37(11):2157-2170. doi: 10.1093/ndt/gfab318.
Anaemia is common in chronic kidney disease (CKD) and assessment of the risks and benefits of new therapies is important.
The Anaemia Study in CKD: Erythropoiesis via a Novel prolyl hydroxylase inhibitor Daprodustat-Non-Dialysis (ASCEND-ND) trial includes adult patients with CKD Stages 3-5, not using erythropoiesis-stimulating agents (ESAs) with screening haemoglobin (Hb) 8-10 g/dL or receiving ESAs with screening Hb of 8-12 g/dL. Participants were randomized to daprodustat or darbepoetin alfa (1:1) in an open-label trial (steering committee- and sponsor-blinded), with blinded endpoint assessment. The co-primary endpoints are mean change in Hb between baseline and evaluation period (average over Weeks 28-52) and time to first adjudicated major adverse cardiovascular (CV) event. Baseline characteristics were compared with those of participants in similar anaemia trials.
Overall, 3872 patients were randomized from 39 countries (median age 67 years, 56% female, 56% White, 27% Asian and 10% Black). The median baseline Hb was 9.9 g/dL, blood pressure was 135/74 mmHg and estimated glomerular filtration rate was 18 mL/min/1.73 m2. Among randomized patients, 53% were ESA non-users, 57% had diabetes and 37% had a history of CV disease. At baseline, 61% of participants were using renin-angiotensin system blockers, 55% were taking statins and 49% were taking oral iron. Baseline demographics were similar to those in other large non-dialysis anaemia trials.
ASCEND-ND will define the efficacy and safety of daprodustat compared with darbepoetin alfa in the treatment of patients with anaemia associated with CKD not on dialysis.
贫血在慢性肾脏病（CKD）中很常见，评估新疗法的风险和益处很重要。
CKD 中的贫血研究：通过新型脯氨酰羟化酶抑制剂 daprodustat-非透析（ASCEND-ND）试验评估红细胞生成，该试验纳入了 3 至 5 期 CKD 成年患者，未使用促红细胞生成素刺激剂（ESA）且筛选血红蛋白（Hb）为 8-10g/dL，或正在接受 ESA 治疗且筛选 Hb 为 8-12g/dL。参与者以 1:1 的比例随机接受 daprodustat 或 darbepoetin alfa（开放标签试验）（指导委员会和赞助商设盲），终点评估设盲。主要复合终点为从基线到评估期（28-52 周平均值）Hb 的平均变化和首次判定的主要不良心血管（CV）事件时间。将基线特征与类似贫血试验的参与者进行比较。
总体而言，来自 39 个国家的 3872 名患者被随机分组（中位年龄 67 岁，56%为女性，56%为白人，27%为亚洲人，10%为黑人）。中位基线 Hb 为 9.9g/dL，血压为 135/74mmHg，估计肾小球滤过率为 18mL/min/1.73m2。在随机分组的患者中，53%未使用 ESA，57%患有糖尿病，37%有心血管疾病史。基线时，61%的参与者正在使用肾素-血管紧张素系统阻滞剂，55%正在服用他汀类药物，49%正在服用口服铁剂。基线人口统计学特征与其他大型非透析性贫血试验相似。
ASCEND-ND 将确定 daprodustat 与 darbepoetin alfa 治疗未透析 CKD 相关贫血患者的疗效和安全性。
