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. 2025 Mar 19;7(5):100997.
doi: 10.1016/j.xkme.2025.100997. eCollection 2025 May.

Vascular Access Thrombosis Events in Patients With Dialysis-Dependent CKD Treated With Vadadustat or Darbepoetin Alfa: The INNO2VATE Trial Program

Wolfgang C Winkelmayer  1 , Steven K Burke  2 , Glenn M Chertow  3 , Kai-Uwe Eckardt  4 , Wenli Luo  2 , Todd Minga  2 , Mark J Sarnak  5 , Prabir Roy-Chaudhury  6
Affiliations

Vascular Access Thrombosis Events in Patients With Dialysis-Dependent CKD Treated With Vadadustat or Darbepoetin Alfa: The INNO2VATE Trial Program

Wolfgang C Winkelmayer et al. Kidney Med. .

Abstract

Rationale & objective: In the global phase 3 INNO2VATE program of patients with dialysis-dependent chronic kidney disease (DD-CKD) and CKD-related anemia (2 trials: patients new to [NCT02865850] and established on maintenance dialysis [NCT02892149]), vadadustat was noninferior to the erythropoiesis-stimulating agent darbepoetin alfa for cardiovascular safety and hemoglobin efficacy. Here, we investigated between-group differences in positively adjudicated vascular access thrombosis (VAT) events.

Study design: Phase 3, global, open-label, randomized, active-controlled clinical trials.

Setting & participants: A total of 3,902 patients who initiated dialysis within the past 16 weeks (incident DD-CKD trial; N = 365) or who had been treated with dialysis for >12 weeks (prevalent DD-CKD trial; N = 3,537).

Intervention: Eligible patients randomized 1:1 to vadadustat or darbepoetin alfa.

Outcomes: Positively adjudicated VAT events.

Results: In the INNO2VATE program, at baseline, 3,590 (92.0%) randomized patients were receiving hemodialysis: 2,709 (69.4%) via an arteriovenous fistula and 340 (8.7%) via an arteriovenous graft. During 6,468 patient-years (PY) of follow-up, there were 426 positively adjudicated VAT events in 266 individual patients, with 146 randomized to vadadustat and 120 randomized to darbepoetin alfa. Corresponding first VAT rates were 4.79 and 3.86 per 100 PY, respectively (rate difference, 0.94; 95% CI, -0.10 to 1.97; hazard ratio [HR], 1.27; 95% CI, 0.99-1.62). When considering first and recurrent events, VAT rates were 6.58 and 6.59 per 100 PY for the vadadustat and darbepoetin alfa groups, respectively (rate difference, -0.01; 95% CI, -1.26 to 1.24; HR, 1.00; 95% CI, 0.83-1.21).

Limitations: Trials were not specifically designed to assess VAT rates; uncertain generalizability to nontrial populations.

Conclusions: In this secondary analysis of the INNO2VATE program in patients with DD-CKD and CKD-related anemia receiving hemodialysis, first VAT rates were numerically higher among patients treated with vadadustat versus darbepoetin alfa but statistically not different. The rates of first and recurrent VAT events were similar between treatment groups.

Keywords: Anemia; chronic kidney disease; hemodialysis; vadadustat; vascular access thrombosis.

Plain language summary

The phase 3 INNO2VATE program studied patients with dialysis-dependent chronic kidney disease (CKD) and CKD-related anemia in 2 trials: one enrolled patients new to dialysis (365 patients) and another studied patients who had been treated with dialysis for at least 3 months (3,537 patients). In terms of cardiovascular safety and ability to treat CKD-related anemia, vadadustat and darbepoetin alfa were not meaningfully different. This analysis also looked at how many patients had dialysis access blockage. There were 146 patients with dialysis access blockages in the vadadustat group and 120 in the darbepoetin alfa group. Although the vadadustat group had a marginally higher rate of first blockages, when subsequent dialysis access blockages were also considered, the rates were similar between treatments.

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References

    1. Stauffer M.E., Fan T. Prevalence of anemia in chronic kidney disease in the United States. PLoS One. 2014;9(1) - PMC - PubMed
    1. Hanna R.M., Streja E., Kalantar-Zadeh K. Burden of anemia in chronic kidney disease: beyond erythropoietin. Adv Ther. 2021;38(1):52–75. - PMC - PubMed
    1. Babitt J.L., Lin H.Y. Mechanisms of anemia in CKD. J Am Soc Nephrol. 2012;23(10):1631–1634. - PMC - PubMed
    1. Portolés J., Martín L., Broseta J.J., Cases A. Anemia in chronic kidney disease: from pathophysiology and current treatments, to future agents. Front Med (Lausanne) 2021;8 - PMC - PubMed
    1. Locatelli F., Bárány P., Covic A., et al. Kidney Disease: Improving Global Outcomes guidelines on anaemia management in chronic kidney disease: a European Renal Best Practice position statement. Nephrol Dial Transplant. 2013;28(6):1346–1359. - PubMed

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