Georgios Bristoyiannis1, Nikolaos Germanos2, Dimitrios Grekas3, Christos Hatzidimitriou4, Christos Iatrou5, Dimitrios Memmos6, Spiros Moutafis7, Konstantinos Papachristoforou8, Antonis Papadoniou9, Michalis Pappas10, George A Sakellariou11, Kostas C Siamopoulos12, Konstantinos Sombolos13, Kiriaki Stamatelou14, Charalambos P Stathakis15, Georgios Stavgiannoudakis16, Spiros Stratigis17, Christos Syrganis18, Dimitris Tsakiris19, Dimitris Valis20, Jannis G Vlahojannis21, Dimosthenis Vlassopoulos22. 1. Renal Unit, General Prefectorial Hospital of Kalamata, Kalamata, Greece. 2. RenalUnit, General District Hospital of Agrini, Agrinio, Greece. 3. Renal Unit, American-HellenicEducational Progressive Association (AHEPA) University Hospital, Thessaloniki, Greece. 4. Renal Unit, General Prefectorial Hospital of Xanthi, Xanthi, Greece. 5. Renal Unit, General District Hospital of Nikea, Piraeus, Greece. 6. Renal Unit,Ippokratio University Hospital, Thessaloniki, Greece. 7. Renal Unit, Private Hospital Henry Dunant, Athens, Greece. 8. Renal Unit, Venizelio Hospital, Heraklio, Greece. 9. Renal Unit, Private Clinic lasis, Piraeus, Greece. 10. Renal Unit, Hatzikosta Hospital,Ioannina, Greece. 11. Renal Unit, Papageorgiou Hospital, Thessaloniki, Greece. 12. Department of Internal Medicine, Medical School, University of Ioannina, Ioannina,Greece. 13. Renal Unit, Popanikoloou Hospital, Thessaloniki, Greece. 14. Renal Unit, Kyanos Stavros Hospital, Athens, Greece. 15. Renal Unit, Laïko Hospital, Athens, Greece. 16. Renal Unit, N.I.M.TS. Hospital, Athens, Greece. 17. Renal Unit, General District University Hospital of Heraklio, Crete, Greece. 18. Renal Unit, General Prefectorial Hospital of Volos, Volos, Greece. 19. Renal Unit, General PrefectorialHospital of Veria, Veria, Greece. 20. Renal Unit, General Private Hospital Ygeia, Athens, Greece. 21. Renal Unit, University Hospital of Patras, Patras, Greece. 22. Renal Unit, Amalia Fleming Hospital, Athens, Greece.
Abstract
BACKGROUND: Darbepoetin alfa is an erythropoietis-stimulating glycoprotein with a ∼3-fold longer t1/2 and greater biological activity compared with recombinant human erythropoietin (rHuEPO). OBJECTIVE: The objective of this study was to evaluate the efficacy andtolerability of long-term (24-week) darbepoetin alfa treatment in maintaining hemoglobin (Hb) concentrations in the target range of 10 to 13 g/dL in patients undergoing dialysis; the patients were switched from rHuEPO to a less-frequent dosing regimen of darbepoetin alfa without an increase in dose. METHODS: In this Phase IIlb, open-label, multicenter study, patients withend-stage renal disease (ESRD) undergoing dialysis who were receiving rHuEPO BIW or TIW at baseline were switched to darbepoetin alfa QW; patients receiving rHuEPO QW were switched to darbepoetin alfa Q2W Administration of darbepoetin alfa was by the same route as previous rHuEPO administration (IV or SC). Patients received darbepoetin alfa for 24 weeks, including a 20-week drug titration period followed by a 4-week, stable-dose evaluation period. The mode, dose, and frequency of administration of darbepoetin alfa were compared with those of baseline rHuEPO. Tolerability assessment was based on spontaneous reporting and laboratory tests (hematology, vital sign measurement, iron status, and biochemistry). RESULTS: The study comprised 173 patients who were divided into 2 groups by route of administration (IV group, n = 146; SC group, n = 27). Mean (SE) adjusted increases in Hb concentration from baseline to the evaluation period for patients receiving darbepoetin alfa QW were 0.94 (0.32) g/dL and 0.38 (0.30) g/dL for the IV or SC routes, respectively (P = 0.004 and NS, respectively). For patients receiving darbepoetin alfa Q2W the mean (SE) adjusted increases in Hb concentration were 0.08 (0.53) g/dL and 0.48 (0.35) g/dL for the IV and SC routes, respectively (both, P = NS). No significant differences in IV/SC dose ratio were observed between the 2 routes of administration. In addition, no increases in darbepoetin alfa dose were observed. The most commonly reported adverse events were hypertension (8 patients [5%]) and vascular access thrombosis (4 [2%]). The incidence of treatment-related adverse events was 6 (3%). CONCLUSIONS: Darbepoetin alfa effectively maintained Hb concentrations within the target range without an increase in dose, even at a reduced dosing frequency. Overall, darbepoetin alfa was well tolerated.
BACKGROUND: Darbepoetin alfa is an erythropoietis-stimulating glycoprotein with a ∼3-fold longer t1/2 and greater biological activity compared with recombinant humanerythropoietin (rHuEPO). OBJECTIVE: The objective of this study was to evaluate the efficacy andtolerability of long-term (24-week) darbepoetin alfa treatment in maintaining hemoglobin (Hb) concentrations in the target range of 10 to 13 g/dL in patients undergoing dialysis; the patients were switched from rHuEPO to a less-frequent dosing regimen of darbepoetin alfa without an increase in dose. METHODS: In this Phase IIlb, open-label, multicenter study, patients withend-stage renal disease (ESRD) undergoing dialysis who were receiving rHuEPO BIW or TIW at baseline were switched to darbepoetin alfa QW; patients receiving rHuEPO QW were switched to darbepoetin alfa Q2W Administration of darbepoetin alfa was by the same route as previous rHuEPO administration (IV or SC). Patients received darbepoetin alfa for 24 weeks, including a 20-week drug titration period followed by a 4-week, stable-dose evaluation period. The mode, dose, and frequency of administration of darbepoetin alfa were compared with those of baseline rHuEPO. Tolerability assessment was based on spontaneous reporting and laboratory tests (hematology, vital sign measurement, iron status, and biochemistry). RESULTS: The study comprised 173 patients who were divided into 2 groups by route of administration (IV group, n = 146; SC group, n = 27). Mean (SE) adjusted increases in Hb concentration from baseline to the evaluation period for patients receiving darbepoetin alfa QW were 0.94 (0.32) g/dL and 0.38 (0.30) g/dL for the IV or SC routes, respectively (P = 0.004 and NS, respectively). For patients receiving darbepoetin alfa Q2W the mean (SE) adjusted increases in Hb concentration were 0.08 (0.53) g/dL and 0.48 (0.35) g/dL for the IV and SC routes, respectively (both, P = NS). No significant differences in IV/SC dose ratio were observed between the 2 routes of administration. In addition, no increases in darbepoetin alfa dose were observed. The most commonly reported adverse events were hypertension (8 patients [5%]) and vascular access thrombosis (4 [2%]). The incidence of treatment-related adverse events was 6 (3%). CONCLUSIONS: Darbepoetin alfa effectively maintained Hb concentrations within the target range without an increase in dose, even at a reduced dosing frequency. Overall, darbepoetin alfa was well tolerated.
Authors: C Jacobs; W H Hörl; I C Macdougall; F Valderrábano; I Parrondo; A Segner; I L Abraham Journal: Nephrol Dial Transplant Date: 2000 Impact factor: 5.992