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Clinical Trial
. 2025 Jun 30;40(7):1332-1341.
doi: 10.1093/ndt/gfae273.

Efficacy and safety of daprodustat in patients on peritoneal dialysis in the ASCEND-D trial

Indranil Dasgupta  1   2 , Amy M Meadowcroft  3 , Purav R Bhatt  3 , Anjali Acharya  4 , Michael Aarup  5 , Ricardo Correa-Rotter  6 , Shruti Gupta  7 , Vijay K Kher  8 , Osvaldo M Viera Neto  9 , Anjay Rastogi  10 , Mai Ots-Rosenberg  11 , Brian Rayner  12 , Muh Geot Wong  13 , Sunay Shah  3 , Lin Taft  3 , Ajay K Singh  6   14
Affiliations
Clinical Trial

Efficacy and safety of daprodustat in patients on peritoneal dialysis in the ASCEND-D trial

Indranil Dasgupta et al. Nephrol Dial Transplant. .

Abstract

Background and hypothesis: Daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is approved for treatment of anemia in dialysis patients with CKD in some parts of the world. This subgroup analysis examined the efficacy and safety of daprodustat versus darbepoetin alfa in patients with anemia of CKD undergoing peritoneal dialysis (PD).

Methods: ASCEND-D (NCT02879305) was an open-label, Phase 3 trial; patients with CKD were randomized to daprodustat daily and epoetin alfa (HD patients) or darbepoetin alfa (PD patients). In PD patients, prespecified analyses of the co-primary endpoints of mean change in hemoglobin from baseline to Weeks 28-52 using an ANOVA model and first occurrence of a major cardiovascular event (MACE) using a Cox proportional hazards model were conducted. The secondary endpoints were average monthly intravenous iron dose to Week 52 and treatment-emergent adverse events. Additional post hoc analyses were conducted.

Results: Overall, 340 PD patients (daprodustat n = 171, darbepoetin alfa n = 169) were randomized. Mean age was 53.6 years (±14 SD), 55% male, 56% White. For daprodustat and darbepoetin alfa groups respectively, mean change in hemoglobin was 0.38 and 0.23 g/dL [adjusted mean difference 0.15, 95% confidence interval (CI), -0.04, 0.34], and first occurrence of adjudicated MACE occurred in 40 (23.4%) and 46 (27.2%) patients (HR 0.84; 95% CI, 0.55-1.28). No heterogeneity was observed between PD and HD patients for these endpoints in ASCEND-D. Serum hepcidin was lower with daprodustat; there was no difference in other iron parameters, intravenous iron usage, transfusion requirement, blood pressure, or quality of life. There were no differences in adverse events or incidence of peritonitis between the groups.

Conclusions: This subgroup analysis of the ASCEND-D trial demonstrated comparable efficacy and safety of daprodustat versus darbepoetin alfa in PD patients, supporting its use in the treatment of anemia in these patients.

Keywords: HIF-PHI; anemia; cardiovascular events; chronic kidney disease; peritoneal dialysis.

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Conflict of interest statement

The authors declare the following real or perceived conflicts of interest during the last 3 years in relation to this presentation: I.D. has received research grants from Medtronic and Sanofi, honoraria for advisory boards and speaker meetings from GSK, AstraZeneca, Sanofi, and Vifor. A.M.M. was an employee of and shareholder in GSK at the time the trial was conducted. P.R.B. is an employee of GSK. A.A. reports consultancy fees from GSK. R.C.-R. reports scientific consulting and financial support for participation in clinical trials: AstraZeneca DAPA-CKD trial steering committee, GSK for ASCEND Investigator and National Leader, Novo Nordisk: FLOW national leader and investigator; advisory board member for Boehringer Ingelheim and AbbVie; speaker for AstraZeneca, Janssen, Boehringer Ingelheim, Amgen, Bayer, and Sanofi. S.G. has received research funding from BTG International, AstraZeneca, and NIH NIDDK (K23 DK125672); and is President Emeritus and Co-founder of American Society of Onco-Nephrology, a consultant for Secretome and Proletariat Therapeutics, and serves on GSK's Global Anemia Council. V.K.K. reports fees for an advisory board and speaker program for Sanofi India, Novartis, Torrent, Biocon, Intas, AstraZeneca, Lupin, and Boehringer Ingelheim. A.R. reports grants from GSK. B.R. reports speaker honoraria from Astellas, Servier, AstraZeneca, Boehringer Ingelheim, Brandmed, and Sanofi, and fees from an Astellas advisory board. M.G.W. reports fees from advisory boards, steering committee roles, and scientific presentations from AbbVie, Amgen, Baxter, Chinook, CSL-Behring, Dimerix, Eledon, GSK, Visterra, Alpine, George Clinical, Kira Pharma, Otsuka, and Travere. S.S. and L.T. are employees of and shareholders in GSK. A.K.S. is chair of the publication steering committee for the ASCEND-D trial and reports consultancy fees from GSK, Bayer AG, and Nephrology Times. M.A., O.M.V.N., and M.O.R. have no conflicts to disclose.

Figures

Figure 1:
Figure 1:
Prespecified analysis of change in hemoglobin (Hb) from baseline over time in patients undergoing PD. Error bars show 95% CI. Post-randomization values include on- and off-treatment values. Dashed vertical lines represent the evaluation period (Week 28 to Week 52). Wk, week; EOS, end of study; FU; follow-up. Dapro, daprodustat; Darbe, darbepoetin alfa.
Figure 2:
Figure 2:
Kaplan–Meier plots of post hoc time to first occurrence of adjudicated cardiovascular events, death from any cause, and hospitalization from any cause in patients undergoing PD. Patients at risk were all randomized patients. Dapro, daprodustat; Darbe, darbepoetin alfa.
Figure 3:
Figure 3:
Post hoc on-treatment iron markers over time in patients undergoing PD, peritoneal dialysis.
See this image and copyright information in PMC

References

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