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Updated: Oct 14, 2025
Author Spotlight: Developing a Point-of-Care Hemoglobin Estimation Method for Anemia Management
Published on: January 19, 2024
Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis
Ajay K Singh1, Kevin Carroll1, John J V McMurray1
1From 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.).
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.).
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