N Engl J Med 2021 04;384(17):1601-1612
From the Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin (K.-U.E.); the Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis (R.A.); Gonzalez M.D. and Aswad M.D. Health Care Services, Miami (A. Aswad); Clinical Research Consultants, Kansas City, MO (A. Awad); 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.), Renal Associates, Division of Nephrology, University of Texas Health Science Center at San Antonio, San Antonio (P.P.), and the Section of Nephrology, Baylor College of Medicine, Houston (W.C.W.) - all in Texas; Praxis Medical Research, and the Department of Medicine, Division of General Practice, Faculdade de Medicina do ABC, São Paulo (M.R.B.); Akebia Therapeutics, Cambridge (Y.M.K.F., Z.K., B.J.M., W.L., D.L.V.), and the Division of Nephrology, Tufts Medical Center, Tufts University School of Medicine, Boston (M.J.S.) - both in Massachusetts; the Division of Nephrology, Department of Medicine, Hofstra Northwell School of Medicine, Great Neck (S.F.), and the Division of Nephrology, New York Presbyterian, Queens (B.S.) - both in New York; Nephrology Associates, Augusta (H.H.), and Emory University School of Medicine, Atlanta (J.T.) - both in Georgia; the Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (A.J.); the Department of Medicine, Vanderbilt University Medical Center, Nashville (M.J.K.); the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore (K.M.); Stanford University School of Medicine, Palo Alto, CA (E.F.L., G.M.C.); the Department of Medicine, Memorial University, St. John's, NL, Canada (P.S.P.); Statistics Collaborative, Washington, DC (K.A.W., J.W.); and the Department of Kidney Transplantation-Dialysis Department, Barlicki Memorial Teaching Hospital No. 1, Medical University of Lodz, Lodz, Poland (R.Z.).
Background: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, a class of compounds that stimulate endogenous erythropoietin production.
Methods: We conducted two randomized, open-label, noninferiority phase 3 trials to evaluate the safety and efficacy of vadadustat, as compared with darbepoetin alfa, in patients with anemia and incident or prevalent dialysis-dependent chronic kidney disease (DD-CKD). The primary safety end point, assessed in a time-to-event analysis, was the first occurrence of a major adverse cardiovascular event (MACE, a composite of death from any cause, a nonfatal myocardial infarction, or a nonfatal stroke), pooled across the trials (noninferiority margin, 1. Read More