Vadadustat for treatment of anemia in patients with dialysis-dependent chronic kidney disease receiving peritoneal dialysis
© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
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| Enthalten in: |
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association - 38(2023), 10 vom: 29. Sept., Seite 2358-2367 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sarnak, Mark J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.10.2023 Date Revised 02.10.2023 published: Print ClinicalTrials.gov: NCT02865850, NCT02892149 Citation Status MEDLINE |
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| doi: |
10.1093/ndt/gfad074 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM356000702 |
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| 245 | 1 | 0 | |a Vadadustat for treatment of anemia in patients with dialysis-dependent chronic kidney disease receiving peritoneal dialysis |
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| 500 | |a Date Revised 02.10.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT02865850, NCT02892149 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of the ERA. | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
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| 650 | 4 | |a chronic kidney disease | |
| 650 | 4 | |a hypoxia-inducible factor prolyl hydroxylase inhibitor | |
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| 700 | 1 | |a Agarwal, Rajiv |e verfasserin |4 aut | |
| 700 | 1 | |a Boudville, Neil |e verfasserin |4 aut | |
| 700 | 1 | |a Chowdhury, Pradip C P |e verfasserin |4 aut | |
| 700 | 1 | |a Eckardt, Kai-Uwe |e verfasserin |4 aut | |
| 700 | 1 | |a Gonzalez, Carlos R |e verfasserin |4 aut | |
| 700 | 1 | |a Kooienga, Laura A |e verfasserin |4 aut | |
| 700 | 1 | |a Koury, Mark J |e verfasserin |4 aut | |
| 700 | 1 | |a Ntoso, Kwabena A |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Wenli |e verfasserin |4 aut | |
| 700 | 1 | |a Parfrey, Patrick S |e verfasserin |4 aut | |
| 700 | 1 | |a Vargo, Dennis L |e verfasserin |4 aut | |
| 700 | 1 | |a Winkelmayer, Wolfgang C |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zhiqun |e verfasserin |4 aut | |
| 700 | 1 | |a Chertow, Glenn M |e verfasserin |4 aut | |
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