Vadadustat for treatment of anemia in patients with dialysis-dependent chronic kidney disease receiving peritoneal dialysis

Nephrol Dial Transplant. 2023 Sep 29;38(10):2358-2367. doi: 10.1093/ndt/gfad074.

Abstract

Background: Hypoxia-inducible factor prolyl hydroxylase inhibitors such as vadadustat may provide an oral alternative to injectable erythropoiesis-stimulating agents for treating anemia in patients receiving peritoneal dialysis. In two randomized (1:1), global, phase 3, open-label, sponsor-blind, parallel-group, active-controlled noninferiority trials in patients with dialysis-dependent chronic kidney disease (INNO2VATE), vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and hematological efficacy. Vadadustat's effects in patients receiving only peritoneal dialysis is unclear.

Methods: We conducted a post hoc analysis of patients in the INNO2VATE trials receiving peritoneal dialysis at baseline. The prespecified primary safety endpoint was time to first major cardiovascular event (MACE; defined as all-cause mortality or nonfatal myocardial infarction or stroke). The primary efficacy endpoint was mean change in hemoglobin from baseline to the primary evaluation period (Weeks 24-36).

Results: Of the 3923 patients randomized in the two INNO2VATE trials, 309 were receiving peritoneal dialysis (vadadustat, n = 152; darbepoetin alfa, n = 157) at baseline. Time to first MACE was similar in the vadadustat and darbepoetin alfa groups [hazard ratio 1.10; 95% confidence interval (CI) 0.62, 1.93]. In patients receiving peritoneal dialysis, the difference in mean change in hemoglobin concentrations was -0.10 g/dL (95% CI -0.33, 0.12) in the primary evaluation period. The incidence of treatment-emergent adverse events (TEAEs) was 88.2% versus 95.5%, and serious TEAEs was 52.6% versus 73.2% in the vadadustat and darbepoetin alfa groups, respectively.

Conclusions: In the subgroup of patients receiving peritoneal dialysis in the phase 3 INNO2VATE trials, safety and efficacy of vadadustat were similar to darbepoetin alfa.

Trial registration: ClinicalTrials.gov NCT02865850 NCT02892149.

Keywords: anemia; chronic kidney disease; hypoxia-inducible factor prolyl hydroxylase inhibitor; peritoneal dialysis; vadadustat.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia* / drug therapy
  • Anemia* / etiology
  • Darbepoetin alfa / therapeutic use
  • Erythropoietin* / adverse effects
  • Hematinics* / adverse effects
  • Hemoglobins / analysis
  • Humans
  • Peritoneal Dialysis* / adverse effects
  • Renal Dialysis / adverse effects
  • Renal Insufficiency, Chronic* / chemically induced
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / therapy

Substances

  • Darbepoetin alfa
  • vadadustat
  • Hematinics
  • Hemoglobins
  • Erythropoietin

Associated data

  • ClinicalTrials.gov/NCT02865850
  • ClinicalTrials.gov/NCT02892149