Comparison of darbepoetin alpha and recombinant human erythropoietin for treatment of anemia in pediatric chronic kidney disease: a non-inferiority trial from India

• Published in: European journal of pediatrics 2023-01, Vol.182 (1), p.101-109
• Main Authors: Mazahir, Rufaida, Anand, Kanav, Pruthi, P. K.
• Format: Article
• Language: English
• Subjects: Adolescent; Anemia; Anemia - drug therapy; Anemia - etiology; Child; Child, Preschool; Children; Darbepoetin alfa - adverse effects; Dialysis; Erythropoiesis; Erythropoietin; Erythropoietin - adverse effects; Hematinics - therapeutic use; Hemodialysis; Hemoglobin; Hemoglobins; Humans; India; Infant; Kidney diseases; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - therapy; Medicine; Medicine & Public Health; Patients; Pediatrics; Recombinant Proteins - adverse effects; Renal Dialysis; Renal Insufficiency, Chronic - complications; Safety; Treatment Outcome
• ISSN: 1432-1076; 0340-6199; 1432-1076
• DOI: 10.1007/s00431-022-04650-1

To determine whether or not Darbepoetin alpha (DA) was non-inferior to recombinant human erythropoietin (rHuEPO) in the treatment of anemia in children with chronic kidney disease (CKD) stage 3–5 (on or not on dialysis). This was a randomized, open-label, two-arm, parallel group, active-controlled, non-inferiority trial conducted at a tertiary care center in New Delhi, India. Fifty patients of either gender (aged 1–18 years) with CKD stage 3–5 (on or not on dialysis) who had baseline hemoglobin (Hb) between 9 and 12 g/dL and were on stable erythropoietin therapy for at least 8 weeks were randomized (1:1) to either continue rHuEPO or switch to DA therapy for a period of 28 weeks. Doses were titrated in the initial 23 weeks to maintain the Hb between 11 and 12 g/dL, and efficacy was assessed between weeks 24 and 28. The primary efficacy outcome was the mean change in Hb between baseline and the evaluation period. In the intention-to-treat population ( n  = 50), the adjusted between-group difference in mean Hb change between the baseline and the evaluation period was 0.131 g/dL (95% CI: − 0.439 to 0.719, p  = 0.629). The lower limit of the two-sided 95% CI for the difference in the mean change in Hb between the two treatment groups was well above the pre-specified non-inferiority margin of − 1.0 g/dL. Similar pattern of non-inferiority was seen for per protocol population. The safety profile of DA and rHuEPO was also comparable (injection site pain:rHuEPO-3, DA-7; p -0.296).     Conclusion : DA is non-inferior to rHuEPO for the treatment of anemia of CKD (stage 3–5) in pediatric population with a comparable safety profile.     Trial registration : ClinicalTrials.gov Identifier: NCT04959578 (retrospectively registered), Date: July 13, 2021. What is Known: • Limited studies showing darbepoetin alpha is effective in children as an erythropoiesis stimulating agent. • No RCT from Indian subcontinent addressing this topic. What is New: • Darbepoetin alpha is non inferior to recombinant human erythropoietin for treatment of anemia in children with CKD stage 3-5 (on or not on dialysis) with safety comparable to recombinant human erythropoietin. • A cost reduction of approximately 8.6% per patient by shifting to darbepoetin alpha.