Dasgupta Indranil, Meadowcroft Amy M, Bhatt Purav R, Acharya Anjali, Aarup Michael, Correa-Rotter Ricardo, Gupta Shruti, Kher Vijay K, Neto Osvaldo M Viera, Rastogi Anjay, Ots-Rosenberg Mai, Rayner Brian, Wong Muh Geot, Shah Sunay, Taft Lin, Singh Ajay K
Department of Renal Medicine, University Hospitals of Birmingham NHS Foundation Trust, Birmingham, UK.
Warwick Medical School, University of Warwick, Coventry, UK.
Nephrol Dial Transplant. 2025 Jun 30;40(7):1332-1341. doi: 10.1093/ndt/gfae273.
Daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is approved for treatment of anemia in dialysis patients with CKD in some parts of the world. This subgroup analysis examined the efficacy and safety of daprodustat versus darbepoetin alfa in patients with anemia of CKD undergoing peritoneal dialysis (PD).
ASCEND-D (NCT02879305) was an open-label, Phase 3 trial; patients with CKD were randomized to daprodustat daily and epoetin alfa (HD patients) or darbepoetin alfa (PD patients). In PD patients, prespecified analyses of the co-primary endpoints of mean change in hemoglobin from baseline to Weeks 28-52 using an ANOVA model and first occurrence of a major cardiovascular event (MACE) using a Cox proportional hazards model were conducted. The secondary endpoints were average monthly intravenous iron dose to Week 52 and treatment-emergent adverse events. Additional post hoc analyses were conducted.
Overall, 340 PD patients (daprodustat n = 171, darbepoetin alfa n = 169) were randomized. Mean age was 53.6 years (±14 SD), 55% male, 56% White. For daprodustat and darbepoetin alfa groups respectively, mean change in hemoglobin was 0.38 and 0.23 g/dL [adjusted mean difference 0.15, 95% confidence interval (CI), -0.04, 0.34], and first occurrence of adjudicated MACE occurred in 40 (23.4%) and 46 (27.2%) patients (HR 0.84; 95% CI, 0.55-1.28). No heterogeneity was observed between PD and HD patients for these endpoints in ASCEND-D. Serum hepcidin was lower with daprodustat; there was no difference in other iron parameters, intravenous iron usage, transfusion requirement, blood pressure, or quality of life. There were no differences in adverse events or incidence of peritonitis between the groups.
This subgroup analysis of the ASCEND-D trial demonstrated comparable efficacy and safety of daprodustat versus darbepoetin alfa in PD patients, supporting its use in the treatment of anemia in these patients.
达普司他是一种口服低氧诱导因子脯氨酰羟化酶抑制剂，在世界某些地区已被批准用于治疗慢性肾脏病（CKD）透析患者的贫血。该亚组分析研究了达普司他与阿法依泊汀在接受腹膜透析（PD）的CKD贫血患者中的疗效和安全性。
ASCEND-D（NCT02879305）是一项开放标签的3期试验；CKD患者被随机分为每日服用达普司他组和依泊汀α组（血液透析患者）或阿法依泊汀组（腹膜透析患者）。对于腹膜透析患者，使用方差分析模型对从基线到第28 - 52周血红蛋白平均变化的共同主要终点以及使用Cox比例风险模型对首次发生的主要心血管事件（MACE）进行预先指定的分析。次要终点是到第52周的平均每月静脉铁剂量和治疗中出现的不良事件。进行了额外的事后分析。
总体而言，340名腹膜透析患者（达普司他组n = 171，阿法依泊汀组n = 169）被随机分组。平均年龄为53.6岁（±14标准差），55%为男性，56%为白人。达普司他组和阿法依泊汀组的血红蛋白平均变化分别为0.38和0.23 g/dL [调整后平均差异0.15，95%置信区间（CI）， - 0.04，0.34]，首次判定的MACE分别发生在40名（23.4%）和46名（27.2%）患者中（风险比0.84；95% CI，0.55 - 1.28）。在ASCEND-D试验中，腹膜透析患者和血液透析患者在这些终点上未观察到异质性。达普司他组的血清铁调素较低；其他铁参数、静脉铁使用、输血需求、血压或生活质量方面没有差异。两组之间不良事件或腹膜炎发生率没有差异。
ASCEND-D试验的该亚组分析表明，达普司他与阿法依泊汀在腹膜透析患者中的疗效和安全性相当，支持其用于治疗这些患者的贫血。
