SP556PHARMACY BASED DOSING OF DARBEPOETIN: A RANDOMIZED CONTROLLED TRIAL IN HEMODIALYSIS PATIENTS

Abstract

Introduction and Aims: In patients with chronic kidney disease, anemia is treated with erythropoietin analogues. For erythropoietin analogues to be most effective, adequate iron levels are required. Treatment guidelines suggest a target range for hemoglobin levels in hemodialysis patients of 6.8 to 7.4 mmol/l [1]. Lower hemoglobin levels are associated with diminished quality of life and increased cardiovascular problems in patients with cardiovascular comorbidity. Higher levels, especially values above 8.1 mmol/l, are associated with increased cardiovascular mortality [2,3]. Previously, only 23% of all hemodialysis patients in our hospital had actual hemoglobin levels within target range. In this randomized, controlled trial, a treatment algorithm was developed for darbepoetin and intravenous iron sucrose, with the intention to improve the percentage of hemodialysis patients within hemoglobin target range. Secondary end points were percentage of patients with hemoglobin levels above 8.1 mmol/l, and percentage of patients with adequate iron levels. Methods: Two hundred patients were randomized (n=100 for intervention and control group). Study duration was thirteen months. Adequate iron levels were defined as transferrin saturation of at least 20% combined with serum ferritin levels between 200 and 500 mcg/l. In the control group, darbepoetin and iron sucrose dosages were adjusted by the treating nephrologist as usual. In the intervention group, dosages of darbepoetin and iron sucrose were adjusted by the pharmacist, based on a treatment algorithm developed by three of the authors (FJO, CFMH, and YCS). In this algorithm previous and actual dosages of darbepoetin and iron, and serum levels of hemoglobin, transferrin saturation and ferritin were included. Statistical analysis was performed with SPSS (PASW statistics 18.0). Median and non‐parametric tests (Mann‐Whitney U test) were used, as data were not distributed normally. As defined in the protocol, fifteen patients were excluded from analysis due to missing data (less than three laboratory analyses during the study period, n=6 in the intervention group, n=9 in the control group). Results: In the intervention group 38.5% of patients had hemoglobin levels within target range, as compared to 23.1% in the control group (p=0.001). Hemoglobin levels above 8.1 nmol/l were more frequent in the control group versus the intervention group (7.7 versus 0.0% p=0.034). Adequate iron status was 21.1% in the intervention group compared with 8.3% in the control group (p=0.003). Conclusions: In hemodialysis patients, darbepoetin and iron sucrose dosing by treatment algorithm increases the percentage of patients within target range for hemoglobin levels as well as with adequate iron storage.