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Randomized Controlled Trial
. 2023 Sep 29;38(10):2358-2367.
doi: 10.1093/ndt/gfad074.

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

Mark J Sarnak  1 , Rajiv Agarwal  2 , Neil Boudville  3 , Pradip C P Chowdhury  4 , Kai-Uwe Eckardt  5 , Carlos R Gonzalez  6 , Laura A Kooienga  7 , Mark J Koury  8 , Kwabena A Ntoso  9 , Wenli Luo  10 , Patrick S Parfrey  11 , Dennis L Vargo  10 , Wolfgang C Winkelmayer  12 , Zhiqun Zhang  10 , Glenn M Chertow  13
Affiliations
Randomized Controlled Trial

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

Mark J Sarnak et al. Nephrol Dial Transplant. .

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.

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Conflict of interest statement

M.J.S. has received steering committee fees from Akebia Therapeutics, Inc., which were paid to Tufts Medical Center. R.A. reports personal fees and nonfinancial support from Bayer Healthcare Pharmaceuticals Inc., Akebia Therapeutics, Inc., Boehringer Ingelheim, Eli Lilly and Vifor Pharma; has received personal fees from Lexicon and Reata; is a member of data safety monitoring committees for Vertex and Chinook; is a member of steering committees for randomized trials for Akebia Therapeutics, Inc., Bayer and Relypsa; and is a member of adjudication committees for Bayer. He has served as associate editor of the American Journal of Nephrology and Nephrology Dialysis Transplantation, has been an author for UpToDate, and has received research grants from the NIH and the US Veterans Administration. N.B. reports receiving grants from Amgen plus consulting or advisory board fees from Otsuka, AstraZeneca, Vifor, GlaxoSmithKline, FMC and Baxter. P.C.P.C. has no disclosures to report. K.-U.E. has received grant support from Amgen and Fresenius; lecture fees from Astellas Pharma; grant support and lecture fees from AstraZeneca, Bayer and Genzyme; consulting fees from Boehringer Ingelheim; advisory board fees from Retrophin; and grant support, advisory board fees and lecture fees from Vifor Pharma. C.R.G. and L.A.K. have no disclosures to report. M.J.K. reports personal fees from Akebia Therapeutics, Inc., as a consultant and member of steering committees for phase 3 trials of vadadustat; from TG Therapeutics, Inc., as a member of a data safety and monitoring committee; and from GlaxoSmithKline as a consultant and member of its educators’ network. He is also a contributor to BMJ Best Practices. K.A.N. has no disclosures to report. W.L. is an employee of Akebia Therapeutics, Inc. P.S.P. has received personal fees from Akebia Therapeutics, Inc., during the conduct of the trial, and advisory board fees from Vifor Pharma. D.L.V. is an employee of Akebia Therapeutics, Inc. W.C.W. has received steering committee fees from Akebia Therapeutics, Inc.; advisory fees from AstraZeneca, Bayer, Janssen, Merck, Otsuka, Reata and Zydus; steering committee and data safety monitoring fees from Bayer and Merck; and an honorarium for an invited lecture by Pharmacosmos. He receives stipends for being an associate editor for JAMA. He has received research grants from several institutes within the NIH. Z.Z. is an employee of Akebia Therapeutics, Inc. G.M.C. serves on the board of directors for Satellite Healthcare. He has served as a steering committee cochair, member, or advisor with Akebia Therapeutics, Inc., Ardelyx, AstraZeneca, CloudCath, CSL Behring, Durect, Gilead, Miromatrix, Outset, Reata, Renibus, Sanifit, Unicycive and Vertex. He has served as chair or member of DSMB/DMCs with Bayer, Gilead, Mineralys, Palladio and ReCor. He has received research grants from NIAID and NIDDK.

Figures

Graphical Abstract
Graphical Abstract
Figure 1:
Figure 1:
Kaplan–Meier curve of time to first MACE in patients receiving peritoneal dialysis (safety population).
Figure 2:
Figure 2:
Mean change in hemoglobin from baseline during the primary and secondary evaluation periods in patients receiving peritoneal dialysis at baseline in the INNO2VATE trials (randomized population). DA, darbepoetin alfa; LS, least squares; VADA, vadadustat.
Figure 3:
Figure 3:
Mean hemoglobin over time up to Week 156 in patients receiving peritoneal dialysis at baseline in the INNO2VATE trials (randomized population).
See this image and copyright information in PMC

References

    1. Global Burden of Disease Chronic Kidney Disease Collaboration . Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study. Lancet 2020;395:709–33. 10.1016/S0140-6736(20)30045-3. - DOI - PMC - PubMed
    1. Stauffer ME, Fan T.. Prevalence of anemia in chronic kidney disease in the United States. PLoS One 2014;9:e84943. 10.1371/journal.pone.0084943. - DOI - PMC - PubMed
    1. Rastogi A, Lerma EV.. Anemia management for home dialysis including the new US public policy initiative. Kidney Int Suppl (2011) 2021;11:59–69. 10.1016/j.kisu.2020.12.005. - DOI - PMC - PubMed
    1. Kidney Disease: Improving Global Outcomes (KDIGO) . KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl 2012;2:292–8.
    1. Hou YP, Mao XY, Wang C.et al. Roxadustat treatment for anemia in peritoneal dialysis patients: a randomized controlled trial. J Formos Med Assoc 2022;121:529–38. 10.1016/j.jfma.2021.06.004. - DOI - PubMed

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