Efficacy, tolerability and safety of darbepoetin alfa injection for the treatment of anemia associated with chronic kidney disease (CKD) undergoing dialysis: a randomized, phase-III trial

Shubhadeep D Sinha,Pankaj Thakur,Sreenivasa Chary,Vamsi Krishna Bandi,Subhramanyam Sreepada,Bala Reddy Bheemareddy,Vikranth Reddy Pinnamareddy,Rajendra Pandey,Kalpana Mehta,Santosh Durugkar

doi:10.1186/s12882-019-1209-1

Abstract

BackgroundDarbepoetin alfa (DA-α) is a long-acting erythropoiesis-stimulating glycoprotein which has half-life three-fold longer than that of Erythropoietin alfa (EPO). The objective of this study was to compare the efficacy and safety of DA-α injection versus EPO for treating renal anemia amongst Indian patients with end-stage renal disease (ESRD) undergoing dialysis.MethodsPatients of either gender (aged 18–65 years) with ESRD undergoing dialysis who had hemoglobin (Hb) levels < 10 g/dL after receiving EPO were switched to DA-α (0.45 μg/kg) once weekly subcutaneously or EPO 50 IU/kg thrice weekly subcutaneously (centrally randomized 1:1) for 12–24 weeks (correction phase) followed by 12 weeks maintenance phase (for Hb levels ≥10 g/dL). The primary efficacy endpoint was mean change in Hb level from baseline to end of correction phase.ResultsIn the intention-to-treat population (n = 126), the between group difference in mean Hb change was − 0.01 g/dL (95% CI – 0.68 to − 0.66, p = 0.97). After adjusting for covariates, the difference was − 0.2878 g/dL (95% CI -0.936 to0.360). The lower limit of the two-sided 95% CI of primary endpoint was above the pre-specified non-inferiority margin of − 1.0 g/dL. Similar trend of non-inferiority was observed for per-protocol population. Safety profile of DA-α and EPO were observed to be similar.ConclusionOur study results demonstrated that for patients with ESRD undergoing dialysis, administering DA-α at lower dose frequency, is equally effective and well tolerated as EPO for treating renal anemia.Trial registrationCTRI/2012/07/002835 [Registered on: 27/07/2012]; Trial Registered Prospectively.

Highlights

Darbepoetin alfa (DA-α) is a long-acting erythropoiesis-stimulating glycoprotein which has half-life three-fold longer than that of Erythropoietin alfa (EPO)
EPO is approved for the correction of anemia in patients with chronic renal failure, and its use in renal anemia eliminates the need for red cell transfusions, alleviates the symptoms of anemia, improves survival, reduces cardiovascular morbidity, and enhances the quality of life [6, 7]
Patient disposition and baseline characteristics A total of 213 patients who underwent dialysis were screened for anaemia (Fig. 1)

Summary

Introduction

Darbepoetin alfa (DA-α) is a long-acting erythropoiesis-stimulating glycoprotein which has half-life three-fold longer than that of Erythropoietin alfa (EPO). The objective of this study was to compare the efficacy and safety of DA-α injection versus EPO for treating renal anemia amongst Indian patients with end-stage renal disease (ESRD) undergoing dialysis. Erythropoietin alfa (EPO) is a short acting erythropoiesis-stimulating agent (ESA) and has been a primary choice for treating anemia in patients with CKD for the past twenty years [6]. EPO is approved for the correction of anemia in patients with chronic renal failure, and its use in renal anemia eliminates the need for red cell transfusions, alleviates the symptoms of anemia, improves survival, reduces cardiovascular morbidity, and enhances the quality of life [6, 7]. Long-acting ESAs are favored over short-acting ESAs [9]

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