达普司他用于治疗未接受透析患者的贫血
Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis.
作者信息
Singh Ajay K, Carroll Kevin, McMurray John J V, Solomon Scott, Jha Vivekanand, Johansen Kirsten L, Lopes Renato D, Macdougall Iain C, Obrador Gregorio T, Waikar Sushrut S, Wanner Christoph, Wheeler David C, Więcek Andrzej, Blackorby Allison, Cizman Borut, Cobitz Alexander R, Davies Rich, DiMino Tara L, Kler Lata, Meadowcroft Amy M, Taft Lin, Perkovic Vlado
机构信息
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), and Boston University School of Medicine and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.), the School of Public Health, Imperial College London (V.J.), King's College Hospital (I.C.M.), and the Department of Renal Medicine, University College London (D.C.W.), London, and GlaxoSmithKline, Brentford (L.K.) - all in the United Kingdom; George Institute for Global Health, New Delhi, and Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal - both in India (V.J.); Hennepin Healthcare, University of Minnesota, Minneapolis (K.L.J.); Duke University Medical Center, Duke Clinical Research Institute, Durham, NC (R.D.L.); Universidad Panamericana School of Medicine, Mexico City (G.T.O.); the University of Würzburg, Würzburg, Germany (C.W.); the Medical University of Silesia, Katowice, Poland (A.W.); GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., T.L.D., A.M.M., L.T.); and the University of New South Wales, Sydney (V.P.).
出版信息
N Engl J Med. 2021 Dec 16;385(25):2313-2324. doi: 10.1056/NEJMoa2113380. Epub 2021 Nov 5.
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. (Funded by GlaxoSmithKline; ASCEND-ND ClinicalTrials.gov number, NCT02876835.).
背景
达普司他是一种口服的低氧诱导因子脯氨酰羟化酶抑制剂。在未接受透析的慢性肾脏病（CKD）患者中，与传统促红细胞生成剂阿法达贝泊汀相比，达普司他的疗效和安全性尚不清楚。
方法
在这项随机、开放标签、3期试验中，对心血管结局进行盲法判定，我们比较了达普司他与阿法达贝泊汀治疗未接受透析的CKD患者贫血的疗效。主要结局是从基线至第28周至52周血红蛋白水平的平均变化，以及首次发生的主要不良心血管事件（MACE；由任何原因导致的死亡、非致死性心肌梗死或非致死性卒中组成的复合事件）。
结果
总体而言，3872例患者被随机分配接受达普司他或阿法达贝泊汀。两组的平均（±标准差）基线血红蛋白水平相似。从基线至第28周至52周，达普司他组血红蛋白水平的平均（±标准误）变化为每分升0.74±0.02克，阿法达贝泊汀组为每分升0.66±0.02克（差异为每分升0.08克；95%置信区间[CI]，0.03至0.13），达到了预先设定的非劣效界值每分升-0.75克。在中位随访1.9年期间，达普司他组1937例患者中有378例（19.5%）首次发生MACE，阿法达贝泊汀组1935例患者中有371例（19.2%）首次发生MACE（风险比，1.03；95%CI，0.89至1.19），达到了预先设定的非劣效界值1.25。两组不良事件患者的百分比相似。
结论
在未接受透析的CKD和贫血患者中，就从基线开始的血红蛋白水平变化和心血管结局而言，达普司他不劣于阿法达贝泊汀。（由葛兰素史克公司资助；ASCEND-ND临床试验注册号，NCT02876835。）
Zotero 插件