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

July 10, 2021 updated by: Rufaida Mazahir

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Delhi
      • New Delhi, Delhi, India, 110060
        • Sir Ganga Ram Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age 1-18 years.
  2. CKD patients stages 3 to 5 (on or not on dialysis).
  3. Baseline hemoglobin 9 - 12 g/dL.
  4. Subject should have adequate transferrin saturation (≥20%) and serum ferritin (≥100 ng/mL).
  5. 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:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean change in hemoglobin (Hb) between baseline and the evaluation period
Time Frame: 24 -28 week
Hb in mg/dL
24 -28 week

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence of treatment-related adverse events in both groups during study period
Time Frame: 0-28 week
0-28 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rufaida Mazahir

Investigators

  • Principal Investigator: Rufaida Mazahir, MD, FNB, Sir Ganga Ram Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2018

Primary Completion (Actual)

January 31, 2019

Study Completion (Actual)

January 31, 2019

Study Registration Dates

First Submitted

July 3, 2021

First Submitted That Met QC Criteria

July 10, 2021

First Posted (Actual)

July 13, 2021

Study Record Updates

Last Update Posted (Actual)

July 13, 2021

Last Update Submitted That Met QC Criteria

July 10, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EC/01/18/1317

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The IPD might be shared if requested from the sponsor-investigator.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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