Comparison of Darbepoetin Alpha and Recombinant Human Erythropoietin for Treatment of Anemia in Children With Chronic Kidney Disease

Sponsor

Rufaida Mazahir (Other)

Overall Status

Completed

CT.gov ID

NCT04959578

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

4.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Anemia of Chronic Kidney Disease	Drug: Recombinant human erythropoietin Drug: Darbepoetin Alfa	Phase 4

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:

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.
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:

Treatment arm 1: Erythropoietin
Treatment arm 2: Darbepoetin alfa
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Comparison of Darbepoetin Alpha and Recombinant Human Erythropoietin as Erythropoietic Agents for Treatment of Anemia in Pediatric Chronic Kidney Disease Patients

Actual Study Start Date :

Feb 1, 2018

Actual Primary Completion Date :

Jan 31, 2019

Actual Study Completion Date :

Jan 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Erythropoietin Recombinant Human Erythropoietin	Drug: Recombinant human erythropoietin 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.
Experimental: Darbepoetin alfa Darbepoetin Alpha	Drug: Darbepoetin Alfa 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.

Arm

Intervention/Treatment

Active Comparator: Erythropoietin

Recombinant Human Erythropoietin

Drug: Recombinant human erythropoietin

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.

Experimental: Darbepoetin alfa

Darbepoetin Alpha

Drug: Darbepoetin Alfa

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.

Outcome Measures

Primary Outcome Measures

Mean change in hemoglobin (Hb) between baseline and the evaluation period [24 -28 week]
Hb in mg/dL

Secondary Outcome Measures

Incidence of treatment-related adverse events in both groups during study period [0-28 week]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 1-18 years.
CKD patients stages 3 to 5 (on or not on dialysis).
Baseline hemoglobin 9 - 12 g/dL.
Subject should have adequate transferrin saturation (≥20%) and serum ferritin (≥100 ng/mL).
Stable erythropoietin therapy for 8 weeks ( defined as a ≤25% change in prescribed dose, no change in the route of administration and no more than one missed or withheld dose).

Exclusion Criteria:

Subject scheduled for a living-related kidney transplant.
Subject with uncontrolled hypertension.
HIV positive patient.
The patient with known hematologic disease or cause of anemia other than renal disease.
Patient with a history of seizure disorder or received antiepileptic medication for a seizure disorder within 6 months prior to enrolment.
Hyperparathyroidism (Intact parathyroid hormone more than 1500 pg/ml or biopsy proven marrow fibrosis).
Major surgery within 12 weeks.
Active inflammatory disease within 8 weeks of randomization requiring immunosuppressive therapy.
Clinical evidence of malignancy.
Blood transfusion within 8 weeks prior to initiation of therapy.