A randomized study of extended dosing regimens for initiation of epoetin alfa treatment for anemia of chronic kidney disease

Abstract

Background and objectives: Although epoetin alfa is commonly initiated weekly (QW) in anemic chronic kidney disease (CKD) patients, recent evidence indicates that it can be initiated every 2 wk (Q2W) and used in maintenance therapy every 4 wk (Q4W). This study examined the feasibility of initiating epoetin alfa Q4W in anemic CKD patients not receiving dialysis.

Design, setting, participants, & measurements: This open-label study randomized subjects (1:2:2:2) to treatment with epoetin alfa 10,000 IU QW, 20,000 IU Q2W, 20,000 IU Q4W, or 40,000 IU Q4W for 16 wk. Subjects were > or =18 yr, had hemoglobin <11 g/dl, a glomerular filtration rate of 15 to 90 ml/min per 1.73 m(2), and had not received erythropoietic therapy within 8 wk. The primary analysis was a noninferiority comparison of the 40,000 IU Q4W to the 20,000 IU Q2W group in the per-protocol population with respect to hemoglobin change from baseline to the end of study.

Results: Of 262 subjects randomized, 229 comprised the per-protocol population. Mean hemoglobin change from baseline for the 40,000 IU Q4W group (1.24 g/dl) was not inferior to the 20,000 IU Q2W group (1.11 g/dl) with the lower limit of 95% CI, -0.21 g/dl. In the QW, 20,000 IU Q2W, 20,000 IU Q4W, and 40,000 IU Q4W groups, 90%, 87%, 75%, and 86% of subjects, respectively, achieved a hemoglobin increase > or =1 g/dl. Serious adverse events were similar across all groups.

Conclusions: Epoetin alfa can be initiated Q4W in anemic CKD subjects.

Trial registration: ClinicalTrials.gov NCT00212875.

Figure 1.

Subject disposition. QW, once weekly; Q2W, every 2 wk; Q4W, every 4 wk; MITT, modified intent to treat; PP, per protocol. *Other includes subjects moved (n = 1), out of town (n = 1), unable to come for visit (n = 2), randomized but never dosed (n = 1), and randomized in error (n = 1). †Modified intent-to-treat (MITT) population: subjects who were randomized and received at least 1 dose of study medication. ‡Per-protocol population: MITT subjects who met the following criteria: completed study, did not have a major protocol violation, and did not miss ≥25% of scheduled epoetin alfa doses.

Figure 2.

Percentage of subjects with an Hb >11 g/dl or an increase of ≥1 g/dl from baseline, or both, anytime during the study. Based on the modified intent-to-treat population. Hb, hemoglobin; QW, once weekly; Q2W, every 2 wk; Q4W, every 4 wk.

Figure 3.

Mean Hb over time by epoetin alfa group (A) and time to first ≥1-g/dl increase in Hb from baseline (B). Based on the modified intent-to-treat population. Hb, hemoglobin; QW, once weekly; Q2W, every 2 wk; Q4W, every 4 wk.