Randomized, controlled trial of darbepoetin alfa for the treatment of anemia in hemodialysis patients.
BACKGROUND
Darbepoetin alfa (Aranesp; Amgen, Thousand Oaks, CA) is a new erythropoiesis-stimulating protein with a threefold longer terminal half-life than recombinant human erythropoietin (epoetin) in patients with chronic kidney disease (CKD). The purpose of this randomized, double-blind, noninferiority study is to determine whether darbepoetin alfa is as effective as epoetin for the treatment of anemia in hemodialysis patients when administered at a reduced dosing frequency.


METHODS
Patients receiving epoetin therapy were randomized to continue epoetin administered intravenously (IV) three times weekly (n = 338) or change to darbepoetin alfa administered IV once weekly (n = 169). The dose of darbepoetin alfa or epoetin was individually titrated to maintain hemoglobin concentrations within -1.0 to +1.5 g/dL (-10 to +15 g/L) of patients' baseline values and within a range of 9.0 to 13.0 g/dL (90 to 130 g/L) for up to 28 weeks (20-week dose-titration period followed by an 8-week evaluation period). The primary end point was change in hemoglobin level between baseline and the evaluation period (weeks 21 to 28).


RESULTS
Mean changes in hemoglobin levels from baseline to the evaluation period were 0.24 +/- 0.10 (SE) g/dL (2.4 +/- 1.0 g/L) in the darbepoetin alfa group and 0.11 +/- 0.07 g/dL (1.1 +/- 0.7 g/L) in the epoetin group, a difference of 0.13 g/dL (95% confidence interval [CI], -0.08 +/- 0.33 [1.3 g/L; 95% CI, -0.8 to 3.3]). This difference was not statistically significant or clinically relevant despite the reduced frequency of darbepoetin alfa administration. The safety profile of darbepoetin alfa was similar to that of epoetin, and no antibody formation to either treatment was detected.


CONCLUSIONS
These results show that darbepoetin alfa maintains hemoglobin concentrations as effectively and safely as epoetin in patients with CKD, but with a reduced dosing frequency.
Nissenson
Allen R
AR
University of California at Los Angeles Medical Center, Los Angeles, CA 90095, USA. anissenson@mednet.ucla.edu
Swan
Suzanne K
SK
Lindberg
Jill S
JS
Soroka
Steven D
SD
Beatey
Robert
R
Wang
Chao
C
Picarello
Nancy
N
McDermott-Vitak
Anna
A
Maroni
Bradley J
BJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000188:drug therapy*; D002170:Canada; D000068256:Darbepoetin alfa; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000068817:Epoetin Alfa; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000379:methods; D016896:Treatment Outcome; D014481:United States
D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa