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Article Abstract
Rationale & Objective: In the global phase 3 INNOVATE 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 INNOVATE 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 INNOVATE 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051538 | PMC |
| http://dx.doi.org/10.1016/j.xkme.2025.100997 | DOI Listing |
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