Comparison of Darbepoetin Alpha and Recombinant Human Erythropoietin for Treatment of Anemia in Children With Chronic Kidney Disease
Condition: Anemia of Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Anemia
Study type: Interventional
Phase: Phase 4

Summary: 
      The present study was designed to determine whether or not darbepoetin alfa is non-inferior
      to recombinant human erythropoietin in the treatment of anemia in children with chronic
      kidney disease stage 3-5 (on or not on dialysis).
    

Detailed description: 
      PRIMARY OBJECTIVE:

      To demonstrate that Darbepoetin alpha is non-inferior to erythropoietin for the treatment of
      anemia in subjects with chronic kidney disease (CKD) stage 3-5 (on or not on dialysis).

      SECONDARY OBJECTIVE:

      To determine the safety and tolerability of Darbepoetin alpha in the treatment of anemia in
      the pediatric population with CKD stage 3-5.

      STUDY DESIGN:

      An open-label, randomized, non-inferiority study of darbepoetin alpha (DA) and recombinant
      human erythropoietin(rHuEpo) for the treatment of anemia in children with chronic kidney
      disease stages 3 to 5 (on or not on dialysis)

      DURATION OF STUDY:

      The study was conducted over a period of 1 year (from 1st February 2018 to 31st January
      2019).

      STUDY SETTING:

      This study was conducted in the Division of Pediatric Nephrology, Department of Paediatrics,
      Institute of Child Health, Sir Ganga Ram Hospital, New Delhi, India.

      CONSENT:

      A prior written informed consent was obtained from parents/ legal guardians of eligible
      children for participation in the study.

      SAMPLE SIZE CALCULATION:

      The primary objective of the study is to assess the non-inferiority of darbepoetin alfa
      compared with rHuEpo. Using a previous study with similar protocol [1], considering
      darbepoetin alfa and rHuEpo as equipotent, we accepted a type I error of 0.05 and a type II
      error of 0.80 for detecting a true difference. A 1.0 or greater difference in mean change in
      Hb variable between two groups was considered clinically significant. An estimate of standard
      deviation in dependent variables was assumed as 1.5. As a result, we have calculated that
      minimum of 28 patients are needed in each group (total-56) in order to obtain 5% type 1 error
      and a 80% power of detecting a difference of 1.0 or more. However, due to time constraints a
      sample of minimum 15 subjects in each group was planned.

      Note: Sample size estimation was done by powerandsamplesize.com.

      METHODOLOGY:

      The study was conducted in the following phases:

        1. Screening Phase (Visit 1, Day -14 to Day -1) The potential subjects were screened as per
           the inclusion and exclusion criteria only after obtaining written informed consent from
           the parent/subject.

        2. Enrollment and Randomization Phase (Visit 2, Day 0)

           Subjects were randomized in two groups in a 1:1 ratio by computer generated mechanism
           (graphpad.com) as follows:

             1. Treatment arm 1: Erythropoietin

             2. Treatment arm 2: Darbepoetin alfa

        3. Treatment Phase (Visit 3, Day 1 to Visit 8, Day 168) Patients received respective
           treatments for 24 week period and they were followed up every 4 weeks. Both rHuEpo and
           darbepoetin alfa were titrated over the first 23 weeks of the study to maintain the
           subjects' Hb levels between 11 to 12 g/dl without adjusting the dosing frequency. Route
           of administration was subcutaneous. Efficacy was determined between weeks 24 and 28.

      ETHICS APPROVAL The study was approved by the Institutional Ethics Committee of Sir Ganga Ram
      Hospital, New Delhi.
    

Intervention name(s): Recombinant human erythropoietin; Darbepoetin Alfa
Intervention type(s): Drug; Drug
Intervention description(s): Dose, route and schedule was kept same as previous erythropoietin dose at randomization; adjusted as necessary (+/- 25% of the starting dose) to maintain Hb within 11 - 12 g/dL.; Dose conversion (100U erythropoietin = 0.42 mcg darbeopoetin). DA dose was kept once weekly (QW) if previously receiving rHuEpo ≥2 times a week, or Q2W if previously receiving rHuEpo <2 times a week. Dose was adjusted as necessary (+/- 25% of the starting dose) to maintain Hb within 11 - 12 g/dL.
Intervention MeSH terms: Epoetin Alfa; Darbepoetin alfa
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Anemia; Chronic kidney disease; Darbepoetin alpha; Erythropoietin; Pediatric