Vadadustat in Patients with Anemia and Non–Dialysis-Dependent CKD
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| Publicado en: | The New England Journal of Medicine vol. 384, no. 17 (Apr 29, 2021), p. 1589 |
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| Autor principal: | |
| Otros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Publicado: |
Massachusetts Medical Society
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| Acceso en línea: | Citation/Abstract Full Text Full Text - PDF |
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| 001 | 2519375476 | ||
| 003 | UK-CbPIL | ||
| 022 | |a 0028-4793 | ||
| 022 | |a 1533-4406 | ||
| 022 | |a 0096-6762 | ||
| 024 | 7 | |a 10.1056/NEJMoa2035938 |2 doi | |
| 035 | |a 2519375476 | ||
| 045 | 0 | |b d20210429 | |
| 084 | |a 28691 |2 nlm | ||
| 100 | 1 | |a Pergola, Pablo E | |
| 245 | 1 | |a Vadadustat in Patients with Anemia and Non–Dialysis-Dependent CKD | |
| 260 | |b Massachusetts Medical Society |c Apr 29, 2021 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a BackgroundVadadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, a class of drugs that stabilize HIF and stimulate erythropoietin and red-cell production.MethodsIn two phase 3, randomized, open-label, active-controlled, noninferiority trials, we compared vadadustat with the erythropoiesis-stimulating agent (ESA) darbepoetin alfa in patients with non–dialysis-dependent chronic kidney disease (NDD-CKD) not previously treated with an ESA who had a hemoglobin concentration of less than 10 g per deciliter and in patients with ESA-treated NDD-CKD and a hemoglobin concentration of 8 to 11 g per deciliter (in the United States) or 9 to 12 g per deciliter (in other countries). The primary safety end point, assessed in a time-to-event analysis, was the first major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), pooled across the two trials. Secondary safety end points included expanded MACE (MACE plus hospitalization for either heart failure or a thromboembolic event). The primary and key secondary efficacy end points in each trial were the mean change in hemoglobin concentration from baseline during two evaluation periods: weeks 24 through 36 and weeks 40 through 52.ResultsA total of 1751 patients with ESA-untreated NDD-CKD and 1725 with ESA-treated NDD-CKD underwent randomization in the two trials. In the pooled analysis, in which 1739 patients received vadadustat and 1732 received darbepoetin alfa, the hazard ratio for MACE was 1.17 (95% confidence interval [CI], 1.01 to 1.36), which did not meet the prespecified noninferiority margin of 1.25. The mean between-group differences in the change in the hemoglobin concentration at weeks 24 through 36 were 0.05 g per deciliter (95% CI, −0.04 to 0.15) in the trial involving ESA-untreated patients and −0.01 g per deciliter (95% CI, −0.09 to 0.07) in the trial involving ESA-treated patients, which met the prespecified noninferiority margin of −0.75 g per deciliter.ConclusionsVadadustat, as compared with darbepoetin alfa, met the prespecified noninferiority criterion for hematologic efficacy but not the prespecified noninferiority criterion for cardiovascular safety in patients with NDD-CKD. (Funded by Akebia Therapeutics and Otsuka Pharmaceutical; PRO2TECT ClinicalTrials.gov numbers, NCT02648347 and NCT02680574.) | |
| 610 | 4 | |a Akebia Therapeutics Inc | |
| 651 | 4 | |a United States--US | |
| 653 | |a Hemodialysis | ||
| 653 | |a Clinical trials | ||
| 653 | |a Hypoxia-inducible factors | ||
| 653 | |a Hemoglobin | ||
| 653 | |a Cerebral infarction | ||
| 653 | |a Collaboration | ||
| 653 | |a Kidney diseases | ||
| 653 | |a Heart failure | ||
| 653 | |a Hypoxia | ||
| 653 | |a Myocardial infarction | ||
| 653 | |a Confidence intervals | ||
| 653 | |a Erythropoietin | ||
| 653 | |a Thromboembolism | ||
| 653 | |a Drug dosages | ||
| 653 | |a Erythropoiesis | ||
| 653 | |a Patients | ||
| 653 | |a Hydroxylase | ||
| 653 | |a Anemia | ||
| 653 | |a Heart attacks | ||
| 653 | |a Prolyl hydroxylase | ||
| 653 | |a Design | ||
| 653 | |a Safety | ||
| 653 | |a Congestive heart failure | ||
| 653 | |a Dialysis | ||
| 700 | 1 | |a Farag Youssef MK | |
| 700 | 1 | |a Agarwal Rajiv | |
| 700 | 1 | |a Arnold, Susan | |
| 700 | 1 | |a Bako Gabriel | |
| 700 | 1 | |a Block, Geoffrey A | |
| 700 | 1 | |a Burke, Steven | |
| 700 | 1 | |a Castillo, Fausto P | |
| 700 | 1 | |a Jardine, Alan G | |
| 700 | 1 | |a Khawaja Zeeshan | |
| 700 | 1 | |a Koury, Mark J | |
| 700 | 1 | |a Lewis, Eldrin F | |
| 700 | 1 | |a Lin, Tim | |
| 700 | 1 | |a Luo Wenli | |
| 700 | 1 | |a Maroni, Bradley J | |
| 700 | 1 | |a Matsushita Kunihiro | |
| 700 | 1 | |a McCullough, Peter A | |
| 700 | 1 | |a Parfrey, Patrick S | |
| 700 | 1 | |a Roy-Chaudhury, Prabir | |
| 700 | 1 | |a Sarnak, Mark J | |
| 700 | 1 | |a Sharma, Amit | |
| 700 | 1 | |a Spinowitz Bruce | |
| 700 | 1 | |a Tseng, Carol | |
| 700 | 1 | |a Tumlin, James | |
| 700 | 1 | |a Vargo, Dennis L | |
| 700 | 1 | |a Walters, Kimberly A | |
| 700 | 1 | |a Winkelmayer, Wolfgang C | |
| 700 | 1 | |a Wittes Janet | |
| 700 | 1 | |a Eckardt Kai-Uwe |u From Stanford University School of Medicine, Palo Alto, CA (G.M.C., E.F.L.); Renal Associates, San Antonio (P.E.P.), U.S. Renal Care, Plano (G.A.B.), Baylor University Medical Center, Baylor Heart and Vascular Hospital, Baylor Heart and Vascular Institute, Dallas (P.A.M.), and the Section of Nephrology, Baylor College of Medicine, Houston (W.C.W.) — all in Texas; Akebia Therapeutics, Cambridge (Y.M.K.F., S.B., Z.K., W.L., B.J.M., A.S., D.L.V.), and the Division of Nephrology, Tufts Medical Center, Tufts University School of Medicine, Boston (M.J.S.) — both in Massachusetts; the Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis (R.A.); Excellentis Clinical Trial Consultants, George, South Africa (S.A.); Bihor County Hospital Oradea, Oradea, Romania (G.B.); Qway Research, Hialeah, FL (F.P.C.); the Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (A.G.J.); the Department of Medicine, Vanderbilt University Medical Center, Nashville (M.J.K.); Firma Clinical Research, Hunt Valley (T.L.), and the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore (K.M.) — both in Maryland; the Department of Medicine, Memorial University of Newfoundland, St. John’s, Canada (P.S.P.); the Division of Nephrology and Hypertension, University of North Carolina Kidney Center, Chapel Hill, and the W.G. (Bill) Hefner Veterans Affairs Medical Center, Salisbury — both in North Carolina (P.R.-C.); the Division of Nephrology, New York–Presbyterian Queens, Flushing (B.S.); Firma Clinical Research, Chicago (C.T.); Emory University School of Medicine, Atlanta (J.T.); Statistics Collaborative, Washington, DC (K.A.W., J.W.); and the Department of Nephrology and Medical Intensive Care, Charité–Universitätsmedizin Berlin, Berlin (K.-U.E.). | |
| 773 | 0 | |t The New England Journal of Medicine |g vol. 384, no. 17 (Apr 29, 2021), p. 1589 | |
| 786 | 0 | |d ProQuest |t Science Database | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/2519375476/abstract/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text |u https://www.proquest.com/docview/2519375476/fulltext/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/2519375476/fulltextPDF/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |