Skip to main content

Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis.

Publication ,  Journal Article
Singh, AK; Carroll, K; Perkovic, V; Solomon, S; Jha, V; Johansen, KL; Lopes, RD; Macdougall, IC; Obrador, GT; Waikar, SS; Wanner, C; Więcek, A ...
Published in: N Engl J Med
December 16, 2021

BACKGROUND: Among patients with chronic kidney disease (CKD), the use of recombinant human erythropoietin and its derivatives for the treatment of anemia has been linked to a possibly increased risk of stroke, myocardial infarction, and other adverse events. Several trials have suggested that hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors (PHIs) are as effective as erythropoiesis-stimulating agents (ESAs) in increasing hemoglobin levels. METHODS: In this randomized, open-label, phase 3 trial, we assigned patients with CKD who were undergoing dialysis and who had a hemoglobin level of 8.0 to 11.5 g per deciliter to receive an oral HIF-PHI (daprodustat) or an injectable ESA (epoetin alfa if they were receiving hemodialysis or darbepoetin alfa if they were receiving peritoneal dialysis). The two primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 (noninferiority margin, -0.75 g per deciliter) and the first occurrence of a major adverse cardiovascular event (a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), with a noninferiority margin of 1.25. RESULTS: A total of 2964 patients underwent randomization. The mean (±SD) baseline hemoglobin level was 10.4±1.0 g per deciliter overall. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.28±0.02 g per deciliter in the daprodustat group and 0.10±0.02 g per deciliter in the ESA group (difference, 0.18 g per deciliter; 95% confidence interval [CI], 0.12 to 0.24), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 2.5 years, a major adverse cardiovascular event occurred in 374 of 1487 patients (25.2%) in the daprodustat group and in 394 of 1477 (26.7%) in the ESA group (hazard ratio, 0.93; 95% CI, 0.81 to 1.07), which also met the prespecified noninferiority margin for daprodustat. The percentages of patients with other adverse events were similar in the two groups. CONCLUSIONS: Among patients with CKD undergoing dialysis, daprodustat was noninferior to ESAs regarding the change in the hemoglobin level from baseline and cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-D ClinicalTrials.gov number, NCT02879305.).

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

December 16, 2021

Volume

385

Issue

25

Start / End Page

2325 / 2335

Location

United States

Related Subject Headings

  • Stroke
  • Renal Insufficiency, Chronic
  • Renal Dialysis
  • Myocardial Infarction
  • Middle Aged
  • Male
  • Intention to Treat Analysis
  • Hypoxia-Inducible Factor-Proline Dioxygenases
  • Humans
  • Hemoglobins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Singh, A. K., Carroll, K., Perkovic, V., Solomon, S., Jha, V., Johansen, K. L., … ASCEND-D Study Group, . (2021). Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis. N Engl J Med, 385(25), 2325–2335. https://doi.org/10.1056/NEJMoa2113379
Singh, Ajay K., Kevin Carroll, Vlado Perkovic, Scott Solomon, Vivekanand Jha, Kirsten L. Johansen, Renato D. Lopes, et al. “Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis.N Engl J Med 385, no. 25 (December 16, 2021): 2325–35. https://doi.org/10.1056/NEJMoa2113379.
Singh AK, Carroll K, Perkovic V, Solomon S, Jha V, Johansen KL, et al. Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis. N Engl J Med. 2021 Dec 16;385(25):2325–35.
Singh, Ajay K., et al. “Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis.N Engl J Med, vol. 385, no. 25, Dec. 2021, pp. 2325–35. Pubmed, doi:10.1056/NEJMoa2113379.
Singh AK, Carroll K, Perkovic V, Solomon S, Jha V, Johansen KL, Lopes RD, Macdougall IC, Obrador GT, Waikar SS, Wanner C, Wheeler DC, Więcek A, Blackorby A, Cizman B, Cobitz AR, Davies R, Dole J, Kler L, Meadowcroft AM, Zhu X, McMurray JJV, ASCEND-D Study Group. Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis. N Engl J Med. 2021 Dec 16;385(25):2325–2335.

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

December 16, 2021

Volume

385

Issue

25

Start / End Page

2325 / 2335

Location

United States

Related Subject Headings

  • Stroke
  • Renal Insufficiency, Chronic
  • Renal Dialysis
  • Myocardial Infarction
  • Middle Aged
  • Male
  • Intention to Treat Analysis
  • Hypoxia-Inducible Factor-Proline Dioxygenases
  • Humans
  • Hemoglobins