ASCEND-D
Trial question
Is daprodustat noninferior to ESAs for anemia in patients with CKD undergoing dialysis?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
43.0% female
57.0% male
N = 2964
2964 patients (1266 female, 1698 male).
Inclusion criteria: patients with CKD undergoing dialysis and who had a hemoglobin level of 8.0-11.5 g/dL.
Key exclusion criteria: anemia unrelated to CKD; recent cardiovascular event; current or recent cancer; kidney transplant; transferrin saturation; gastrointestinal bleeding; MI or acute coronary syndrome; stroke or TIA ≤ 4 weeks prior to screening through to randomization.
Interventions
N=1487 daprodustat (starting dose of 4-12 mg/day with stepped dose adjustment from 1-24 mg).
N=1477 ESAs (epoetin alfa if receipt of hemodialysis or darbepoetin alfa if receipt of peritoneal dialysis).
Primary outcome
Mean improvement in hemoglobin level from baseline to weeks 28 through 52
0.28 g/dL
0.1 g/dL
0.3 g/dL
0.2 g/dL
0.1 g/dL
0.1 g/dL
0.0 g/dL
Daprodustat
Erythropoiesis-stimulating
agents
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in mean improvement in hemoglobin level from baseline to weeks 28 through 52 (0.28 g/dL vs. 0.1 g/dL; MD 0.18, 95% CI 0.12 to 0.24).
Secondary outcomes
No significant difference in major adverse cardiovascular event (25.2% vs. 26.7%; HR 0.93, 95% CI 0.81 to 1.07).
Significant decrease in major adverse cardiovascular event or thromboembolic event (33.4% vs. 36.8%; HR 0.88, 95% CI 0.78 to 1).
No significant difference in major adverse cardiovascular event or hospitalization for HF (28.6% vs. 29.3%; HR 0.97, 95% CI 0.85 to 1.11).
Safety outcomes
No significant differences in major adverse cardiovascular event, serious adverse events.
Conclusion
In patients with CKD undergoing dialysis and who had a hemoglobin level of 8.0-11.5 g/dL, daprodustat was noninferior to ESAs with respect to mean improvement in hemoglobin level from baseline to weeks 28 through 52.
Reference
Ajay K Singh, Kevin Carroll, Vlado Perkovic et al. Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis. N Engl J Med. 2021 Dec 16;385(25):2325-2335.
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