Using a low, fixed dose of darbepoetin is as effective as using a titrated approach in minimizing the risk for red blood cell transfusion in patients with anemia resulting from nondialysis chronic kidney disease (CKD), a new study finds.
In the phase 3 START-CKD trial, investigators randomly assigned 379 patients with stage 3-5 CKD not on dialysis to receive darbepoetin 0.45 µg/kg every 4 weeks (fixed-dose group) and 377 to receive hemoglobin-based darbepoetin dosing (titration-dose group). Over 2 years, similar proportions of both groups were transfused: 24.1% fixed-dose group vs 24.4% titration-dose group, with no difference in time to first transfusion, Robert Toto, MD, of the University of Texas Southwestern Medical Center in Dallas, Texas, and colleagues reported in the Journal of the American Society of Nephrology.
As expected, the titration-dose group achieved a significantly higher median hemoglobin level (9.9 g/dL) compared with the fixed-dose group (9.4 g/dL). This difference, however, was balanced by a significantly lower median cumulative exposure to the erythropoiesis-stimulating agent (ESA) in the fixed-dose rather than titrated-dose group: median monthly dose 30.9 vs 53.6 µg, respectively, with a between-group difference of -22.1 µg, the investigators reported. High ESA doses have been implicated in the increased risk of cardiovascular events observed when targeting high hemoglobin, among several possibilities.
Although a higher proportion of patients in the titrated-dose group experienced adverse events (9.8% vs 6.9%), the types of adverse events and time to major clinical events were similar between treatment arms. Many patients discontinued darbepoetin when they progressed to end-stage kidney disease and for unknown reasons, the investigators noted.
“Our study results are timely and important in the current healthcare environment, emphasizing improved patient outcomes and better utilization of healthcare resources, and represent an important step in better understanding optimal utilization of ESA in advanced CKD to avoid risks associated with RBC transfusions,” Dr Toto’s team concluded.
Disclosure: This clinical trial was supported by Amgen. Please see the original reference for a full list of authors’ disclosures.
Toto R, Petersen J, Berns JS, Foster Lewis E, Tran Q, Weir MR. A randomized trial of strategies using darbepoetin alfa to avoid transfusions in CKD. J Am Soc Nephrol. 32(2):469-478. doi:10.1681/ASN.2020050556