A randomized controlled study of weekly and biweekly dosing of epoetin alfa in CKD Patients with anemia

Abstract

Background and objectives: In clinical practice, physicians often use once-weekly (QW) and biweekly (Q2W) dosing of epoetin alfa to treat anemia in patients with chronic kidney disease (CKD). Although the literature supports this practice, previous studies were limited by short treatment duration, lack of randomization, or absence of the approved three times per week (TIW) dosing arm. This randomized trial evaluated extended dosing regimens of epoetin alfa, comparing QW and Q2W to TIW dosing in anemic CKD subjects. The primary objective was to show that treatment with epoetin alfa at QW and Q2W intervals was not inferior to TIW dosing.

Design, setting, participants, & measurements: 375 subjects with stage 3 to 4 CKD were randomized equally to the three groups and treated for 44 wk; to explore the impact of changing from TIW to QW administration on hemoglobin (Hb) control and adverse events, subjects on TIW switched to QW after 22 wk. The Hb was measured weekly, and the dose of epoetin alfa was adjusted to achieve and maintain an Hb level of 11.0 to 11.9 g/dl.

Results: Both the QW and Q2W regimens met the primary efficacy endpoint. More subjects in the TIW group than in the QW and Q2W groups exceeded the Hb ceiling. Adverse events were similar across treatment groups and consistent with the morbidities of CKD patients.

Conclusions: Administration of epoetin alfa at QW and Q2W intervals are potential alternatives to TIW dosing for the treatment of anemia in stage 3 to 4 CKD subjects.

Trial registration: ClinicalTrials.gov NCT00440557.

Figures

Figure 1.

Patient disposition and study schema. TIW, three times per week; QW, once weekly; Q2W, biweekly; Hb, hemoglobin; mITT, modified intent to treat. amITT population: subjects who were randomized and had at least one postrandomization Hb value. bPer-protocol population: subjects who received at least 75% of the intended doses during the first 22 wk of the study (i.e., at least 50 doses for the TIW group, at least 17 doses for the QW group, and at least 9 doses for the TIW group) before withdrawal from the study, receipt of a transfusion, or initiation of dialysis, whichever occurred earliest, and who had no major protocol deviations.

Figure 2.

Mean Hb over the first 22 (A) and 44 wk (B) of treatment by epoetin alfa treatment groups. TIW, three times weekly; QW, once weekly; Q2W, biweekly.