1. A Randomized Trial of Strategies Using Darbepoetin Alfa To Avoid Transfusions in CKD.
- Author
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Toto R, Petersen J, Berns JS, Lewis EF, Tran Q, and Weir MR
- Subjects
- Aged, Aged, 80 and over, Algorithms, Anemia complications, Anemia diagnosis, Drug Administration Schedule, Female, Hemoglobins metabolism, Humans, Male, Middle Aged, Renal Insufficiency, Chronic therapy, Anemia therapy, Darbepoetin alfa administration & dosage, Erythrocyte Transfusion, Hematinics administration & dosage, Renal Insufficiency, Chronic complications
- Abstract
Background: Exposure to high doses or a high cumulative dose of erythropoiesis-stimulating agents (ESAs) may contribute to cardiovascular events in patients with CKD and anemia. Whether using a low fixed ESA dose versus dosing based on a hemoglobin-based, titration-dose algorithm in such patients might reduce risks associated with high ESA doses and decrease the cumulative exposure-while reducing the need for red blood cell transfusions-is unknown., Methods: In this phase-3, randomized trial involving 756 adults with stage-3 to -5 CKD and anemia, we evaluated incidence of red blood cell transfusions for participants randomized to receive darbepoetin given as a fixed dose (0.45 µ g/kg every 4 weeks) versus administered according to a hemoglobin-based, titration-dose algorithm, for up to 2 years. Participants received transfusions as deemed necessary by the treating physician., Results: There were 379 patients randomized to the fixed-dose group, and 377 to the titration-dose group. The percentage of participants transfused did not differ (24.1% and 24.4% for the fixed-dose and titration-dose group, respectively), with similar time to first transfusion. The titration-dose group achieved significantly higher median hemoglobin (9.9 g/dl) compared with the fixed-dose group (9.4 g/dl). The fixed-dose group had a significantly lower median cumulative dose of darbepoetin (median monthly dose of 30.9 µ g) compared with the titration-dose group (53. 6 µg median monthly dose). The FD and TD group received a median (Q1, Q3) cumulative dose per 4 weeks of darbepoetin of 30.9 (21.8, 40.0) µ g and 53.6 (31.1, 89.9) µ g, respectively; the median of the difference between treatment groups was -22.1 (95% CI, -26.1 to -18.1) µ g., Conclusions: These findings indicate no evidence of difference in incidence of red blood cell transfusion for a titration-dose strategy versus a fixed-dose strategy for darbepoetin. This suggests that a low fixed dose of darbepoetin may be used as an alternative to a dose-titration approach to minimize transfusions, with less cumulative dosing., (Copyright © 2021 by the American Society of Nephrology.)
- Published
- 2021
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