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Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis.
N Engl J Med. 2021 12 16; 385(25):2325-2335.NEJM

Abstract

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.).

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Singh AK
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Carroll K
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Perkovic V
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Solomon S
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Jha V
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Johansen KL
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Lopes RD
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Macdougall IC
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Obrador GT
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Waikar SS
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Wanner C
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Wheeler DC
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Więcek A
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Blackorby A
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Cizman B
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Cobitz AR
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Davies R
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Dole J
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Kler L
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Meadowcroft AM
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
Zhu X
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
McMurray JJV
From Brigham and Women's Hospital (A.K.S., S.S.), Harvard Medical School (A.K.S., S.S.), Boston University School of Medicine (S.S.W.), and Boston Medical Center (S.S.W.) - all in Boston; KJC Statistics, Cheadle (K.C.), 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, GlaxoSmithKline, Brentford (L.K. X.Z.), and the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow (J.J.V.M.) - all in the United Kingdom; University of New South Wales, Sydney (V.P.); George Institute for Global Health, New Delhi (V.J.) and Prasanna School of Public Health (V.J.), Manipal Academy of Higher Education, Manipal (V.J.) - both in India; 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); University of Würzburg, Würzburg, Germany (C.W.); Medical University of Silesia, Katowice, Poland (A.W.); and GlaxoSmithKline, Collegeville, PA (A.B., B.C., A.R.C., R.D., J.D., A.M.M.).
ASCEND-D Study Group
No affiliation info available

MeSH

AgedAnemiaBarbituratesCardiovascular DiseasesDarbepoetin alfaEpoetin AlfaFemaleGlycineHematinicsHemoglobinsHumansHypoxia-Inducible Factor-Proline DioxygenasesIntention to Treat AnalysisMaleMiddle AgedMyocardial InfarctionRenal DialysisRenal Insufficiency, ChronicStroke

Pub Type(s)

Clinical Trial, Phase III
Comparative Study
Equivalence Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34739194

Clinical Trial Links

Clinical trial which this article describes

Citation

Singh, Ajay K., et al. "Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis." The New England Journal of Medicine, vol. 385, no. 25, 2021, pp. 2325-2335.
Singh AK, Carroll K, Perkovic V, et al. Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis. N Engl J Med. 2021;385(25):2325-2335.
Singh, A. K., Carroll, K., Perkovic, V., Solomon, S., Jha, V., Johansen, K. L., Lopes, R. D., Macdougall, I. C., Obrador, G. T., Waikar, S. S., Wanner, C., Wheeler, D. C., Więcek, A., Blackorby, A., Cizman, B., Cobitz, A. R., Davies, R., Dole, J., Kler, L., ... McMurray, J. J. V. (2021). Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis. The New England Journal of Medicine, 385(25), 2325-2335. https://doi.org/10.1056/NEJMoa2113379
Singh AK, et al. Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis. N Engl J Med. 2021 12 16;385(25):2325-2335. PubMed PMID: 34739194.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis. AU - Singh,Ajay K, AU - Carroll,Kevin, AU - Perkovic,Vlado, AU - Solomon,Scott, AU - Jha,Vivekanand, AU - Johansen,Kirsten L, AU - Lopes,Renato D, AU - Macdougall,Iain C, AU - Obrador,Gregorio T, AU - Waikar,Sushrut S, AU - Wanner,Christoph, AU - Wheeler,David C, AU - Więcek,Andrzej, AU - Blackorby,Allison, AU - Cizman,Borut, AU - Cobitz,Alexander R, AU - Davies,Rich, AU - Dole,Jo, AU - Kler,Lata, AU - Meadowcroft,Amy M, AU - Zhu,Xinyi, AU - McMurray,John J V, AU - ,, Y1 - 2021/11/05/ PY - 2021/11/6/pubmed PY - 2021/12/29/medline PY - 2021/11/5/entrez SP - 2325 EP - 2335 JF - The New England journal of medicine JO - N Engl J Med VL - 385 IS - 25 N2 - 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.). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/34739194/Daprodustat_for_the_Treatment_of_Anemia_in_Patients_Undergoing_Dialysis_ DB - PRIME DP - Unbound Medicine ER -