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

ABSTRACT: 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.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.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.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.

SUBMITTER: Pergola PE

PROVIDER: S-EPMC2774960 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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

Pergola Pablo E PE Gartenberg Gary G Fu Min M Wolfson Marsha M Rao Sudhakar S Bowers Peter P

Clinical journal of the American Society of Nephrology : CJASN 20090917 11

<h4>Background and objectives</h4>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 dos ...[more]

PMID: 19808215

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Project description:BACKGROUND AND OBJECTIVES:This study was conducted to compare the safety and efficacy of intravenous epoetin alfa-epbx, an epoetin alfa biosimilar, to epoetin alfa in patients on hemodialysis with ESKD and anemia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:In this 24-week, multicenter, double-blind comparative efficacy and safety study, 612 patients on hemodialysis with ESKD and anemia who had stable hemoglobin and were receiving stable doses of intravenous epoetin alfa were randomized (1:1) to intravenous epoetin alfa or epoetin alfa-epbx. Dosing was adjusted according to the epoetin alfa prescribing information. The coprimary efficacy end points were the least squares mean difference between the two treatments in mean weekly hemoglobin level and mean weekly epoetin dose per kilogram of body weight during the last 4 weeks of treatment. RESULTS:The least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly hemoglobin was -0.12 g/dl and the 95% confidence interval (-0.25 to 0.01) was contained within the prespecified equivalence margin (-0.5 to 0.5 g/dl). The least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly epoetin dose per kilogram of body weight was 0.37 U/kg per week, and the 95% confidence interval (-10.40 to 11.13) was contained within the prespecified equivalence margin (-45 to 45 U/kg per week). Incidences of adverse events (77.1% versus 75.3%), serious adverse events (24.9% versus 27.0%), and deaths (n=5 versus 6) were similar between the epoetin alfa-epbx and epoetin alfa groups, respectively. Five patients tested positive for anti-recombinant human erythropoietin antibodies at baseline, and two additional patients (n=1 per group) developed anti-recombinant human erythropoietin antibodies while on study treatment. All patients tested negative for neutralizing antibodies, and no patient in either group experienced an event of pure red cell aplasia. CONCLUSIONS:This 24-week, comparative, clinical trial in patients on hemodialysis with ESKD and anemia demonstrated there is no clinically meaningful difference in efficacy or safety between epoetin alfa-epbx and epoetin alfa.

Project description:Anaemia is a common complication of chronic kidney disease and prevalence increases with declining renal function. Renal anaemia has significant implications for the well-being and quality of life of patients and impacts on morbidity and mortality. Anaemia can be well managed by therapy with erythropoiesis-stimulating agents (ESAs). Previous clinical trials have shown that the only human cell-line-derived ESA, epoetin delta, is well tolerated and effective in maintaining haemoglobin levels in anaemic patients with chronic kidney disease. The half-life of epoetin delta suggests that administration of this agent is feasible once weekly and once every two weeks. We report on the design and rationale of a trial to compare once weekly vs. twice weekly, and once weekly vs. once every two weeks dosing of epoetin delta.This is a randomized, open-label, multicentre trial. Patients aged 18 years or above with chronic kidney disease (Stages 3-5) are eligible to enter this trial. Two groups of patients form the trial population, those naïve to ESA therapy and those previously stable on ESA therapy. There are two primary objectives of this trial: 1) to demonstrate non-inferiority between twice weekly and once weekly dosing of epoetin delta in previously naïve patients (assessed by haemoglobin at Week 24); 2) to demonstrate non-inferiority between once weekly and once every two weeks dosing in previously stable patients (assessed by average haemoglobin over Weeks 16-24). Among the secondary analyses will be assessments of haematocrit, number(%) of patients meeting predefined targets for haemoglobin and haematocrit levels, and comparisons of average dose. All patients will receive study medication for 24 weeks and dose will be adjusted according to a predefined algorithm to achieve and maintain haemoglobin >or= 11 g/dL. All patients completing this trial are eligible to enter a 2-year follow-up study to enable monitoring of emergent adverse events, anti-erythropoietin antibody responses, maintenance of efficacy and changes in diabetic retinopathy status.To our knowledge, this trial is the first to randomize ESA-naïve patients to different dosing regimens of the same ESA. Data generated will help in guiding the most appropriate dosing frequency for epoetin delta, particularly in those patients new to epoetin delta therapy.ClinicalTrials.gov: NCT00450333.

Project description:IntroductionThere is scant real-world information on switching treatment for anemia associated with chronic kidney disease (CKD) from methoxy polyethylene glycol-epoetin beta (PEG-Epo) to darbepoetin alfa (DA). TRANSFORM was a multi-center, observational study designed to describe the time course of hemoglobin (Hb) concentration (primary outcome measure) and other parameters of clinical management of anemia in European hemodialysis patients in clinical practice before and after a switch from PEG-Epo to DA.MethodsEligible subjects were adult patients with CKD dialyzed at European dialysis centers for ≥26 weeks and treated with PEG-Epo for ≥14 weeks immediately prior to being switched to DA and no earlier than January 2011. Erythropoiesis-stimulating agent doses and Hb values were recorded for the 14-week pre-switch and 26-week post-switch periods.ResultsOf the 1,027 eligible patients enrolled at 42 hemodialysis centers in 7 European countries, 785 were included in analyses. Mean (95% confidence interval [CI]) Hb was generally stable: 11.19 (11.11, 11.26), 11.48 (11.40, 11.57), and 11.29 (11.20, 11.37) g/dL at month -1 pre-switch and months 3 and 6 post-switch, respectively. The geometric mean (95% CI) PEG-Epo dose at month -1 was 27.4 (26.0, 28.8) µg/week; DA dose was 29.4 (27.9, 30.9), 23.3 (21.9, 24.9), and 25.6 (24.1, 27.1) µg/week at months 1, 4, and 6, respectively. The geometric mean (95% CI) dose ratio at switching was 1.06 (1.01, 1.11). When stratifying by dose-ratio categories <0.8, 0.8-1.2, and >1.2 at switching, mean DA dose and Hb converged within narrow ranges by month 6 post-switch: 23.9-27.0 µg/week and 11.1-11.5 g/dL, respectively. Hb excursions <10 g/dL were less frequent post-switch versus pre-switch.ConclusionMean Hb values remained within a narrow range following switching from PEG-Epo to DA in this population of hemodialysis patients. Time trends of mean Hb and DA dose indicate that physicians titrated DA doses post-switch, to attain Hb concentrations comparable to those attained pre-switch with PEG-Epo.

Project description:Background and objectivesLarge, randomized, controlled trials targeting higher hemoglobin level with erythropoiesis-stimulating agents for Western patients with CKD showed harm. However, the effect of anemia correction using erythropoiesis-stimulating agents may differ between CKD subpopulations. The Prevention of ESKD by Darbepoetin Alfa in CKD Patients with Non-diabetic Kidney Disease study, a multicenter, randomized, open-label, parallel-group study, aimed to examine the effect of targeting hemoglobin levels of 11-13 g/dl using darbepoetin alfa with reference to a low-hemoglobin target of 9-11 g/dl on kidney outcome in patients with advanced CKD without diabetes in Japan.Design, setting, participants, & measurementsWe enrolled 491 patients with CKD without diabetes, and an eGFR of 8-20 ml/min per 1.73 m2. Of these 491 patients, 239 and 240 were ultimately assigned to the high- and low-hemoglobin groups, respectively (12 patients were excluded). The primary outcome was a kidney composite end point (starting maintenance dialysis, kidney transplantation, eGFR≤6 ml/min per 1.73 m2, and 50% reduction in eGFR).ResultsMean hemoglobin levels were 11.2±1.1 and 10.0±0.9 g/dl in the high- and low-hemoglobin groups, respectively, during the mean study period of 73.5±29.7 weeks. The kidney composite end point occurred in 105 (44%) and 116 (48%) patients in the high- and low-hemoglobin groups, respectively (log-rank test; P=0.32). The adjusted Cox proportional hazards model showed that the hazard ratio for the high- versus low-hemoglobin group was 0.78 (95% confidence interval, 0.60 to 1.03; P=0.08). Cardiovascular events occurred in 19 (8%) and 16 (7%) patients in each group, respectively, with no significant between-group difference (log-rank test; P=0.66).ConclusionsTargeting a higher hemoglobin level (11-13 g/dl) with darbepoetin alfa did not improve kidney outcome compared with targeting a lower hemoglobin level (9-11 g/dl) in patients with advanced CKD without diabetes.Clinical trial registry name and registration numberPrevention of ESKD by Darbepoetin Alfa in CKD Patients with Non-diabetic Kidney Disease (PREDICT), NCT01581073.

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

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

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