美国布列根和妇女医院Ajay K. Singh团队研究了达普司他治疗未接受透析患者贫血的疗效。该项研究成果发表在2021年11月5日出版的《新英格兰医学杂志》上。

达普司他是一种口服缺氧诱导因子脯氨酰羟化酶抑制剂。在未接受透析的慢性肾病（CKD）患者中，达普司他与常规促红细胞生成素阿法达贝泊相比的有效性和安全性尚不清楚。

在这项随机、开放标签、临床3期试验中，研究组比较了达普司他和阿法达贝泊治疗未接受透析的CKD患者贫血的疗效。主要结局是血红蛋白水平从基线到第28-52周的平均变化和首次发生重大不良心血管事件（MACE；由全因死亡、非致命性心肌梗死或非致命性中风组成的综合结局）。

共有3872名患者被随机分配接受达普司他或阿法达贝泊治疗。两组的平均基线血红蛋白水平相似。从基线检查到第28-52周，达普司他组的血红蛋白水平平均变化为0.74 g/dL，阿法达贝泊组为0.66 g/dL，符合预先规定的非劣效性范围（-0.75 g/dL）。在1.9年的中位随访期间，达普司他组1937名患者中有378名（19.5%）出现首次MACE，阿法达贝泊组1935名患者中有371名（19.2%），风险比为1.03，符合预先规定的非劣效性范围（1.25）。两组患者发生不良事件的百分比相似。

研究结果表明，在未接受透析的CKD和贫血患者中，达普司他治疗在血红蛋白水平与基线水平的变化以及心血管预后方面均不劣于阿法达贝泊。

附：英文原文

Title: Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis | NEJM

Author: Ajay K. Singh, M.B., B.S., M.B.A.,, Kevin Carroll, Ph.D.,, John J.V. McMurray, M.D.,, Scott Solomon, M.D.,, Vivekanand Jha, M.D.,, Kirsten L. Johansen, M.D.,, Renato D. Lopes, M.D., Ph.D.,, Iain C. Macdougall, M.D.,, Gregorio T. Obrador, M.D.,, Sushrut S. Waikar, M.D.,, Christoph Wanner, M.D.,, David C. Wheeler, M.B., Ch.B., M.D.,, Andrzej Wicek, M.D., Ph.D.,, Allison Blackorby, M.Sc.,, Borut Cizman, M.D.,, Alexander R. Cobitz, M.D., Ph.D.,, Rich Davies, M.Sc.,, Tara L. DiMino, M.D.,, Lata Kler, Ph.D.,, Amy M. Meadowcroft, Pharm.D.,, Lin Taft, Ph.D.,, and Vlado Perkovic, M.B., B.S., Ph.D.

Issue&Volume: 2021-11-05

Abstract:

Background

Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. In patients with chronic kidney disease (CKD) who are not undergoing dialysis, the efficacy and safety of daprodustat, as compared with the conventional erythropoiesis-stimulating agent darbepoetin alfa, are unknown.

Methods

In this randomized, open-label, phase 3 trial with blinded adjudication of cardiovascular outcomes, we compared daprodustat with darbepoetin alfa for the treatment of anemia in patients with CKD who were not undergoing dialysis. The primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 and the first occurrence of a major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke).

Results

Overall, 3872 patients were randomly assigned to receive daprodustat or darbepoetin alfa. The mean (±SD) baseline hemoglobin levels were similar in the two groups. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.74±0.02 g per deciliter in the daprodustat group and 0.66±0.02 g per deciliter in the darbepoetin alfa group (difference, 0.08 g per deciliter; 95% confidence interval [CI], 0.03 to 0.13), which met the prespecified noninferiority margin of 0.75 g per deciliter. During a median follow-up of 1.9 years, a first MACE occurred in 378 of 1937 patients (19.5%) in the daprodustat group and in 371 of 1935 patients (19.2%) in the darbepoetin alfa group (hazard ratio, 1.03; 95% CI, 0.89 to 1.19), which met the prespecified noninferiority margin of 1.25. The percentages of patients with adverse events were similar in the two groups.

Conclusions

Among patients with CKD and anemia who were not undergoing dialysis, daprodustat was noninferior to darbepoetin alfa with respect to the change in the hemoglobin level from baseline and with respect to cardiovascular outcomes.

DOI: 10.1056/NEJMoa2113380

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2113380