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

NCT ID: NCT04959578

Last Updated: 2021-07-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-01

Study Completion Date

2019-01-31

Brief Summary

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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

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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.

Conditions

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Anemia of Chronic Kidney Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Erythropoietin

Recombinant Human Erythropoietin

Group Type ACTIVE_COMPARATOR

Recombinant human erythropoietin

Intervention Type DRUG

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.

Darbepoetin alfa

Darbepoetin Alpha

Group Type EXPERIMENTAL

Darbepoetin Alfa

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

1 Year

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rufaida Mazahir

OTHER

Sponsor Role lead

Responsible Party

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Rufaida Mazahir

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Rufaida Mazahir, MD, FNB

Role: PRINCIPAL_INVESTIGATOR

Sir Ganga Ram Hospital

Locations

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Sir Ganga Ram Hospital

New Delhi, National Capital Territory of Delhi, India

Site Status

Countries

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India

References

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Warady BA, Arar MY, Lerner G, Nakanishi AM, Stehman-Breen C. Darbepoetin alfa for the treatment of anemia in pediatric patients with chronic kidney disease. Pediatr Nephrol. 2006 Aug;21(8):1144-52. doi: 10.1007/s00467-006-0071-0. Epub 2006 May 25.

Reference Type BACKGROUND
PMID: 16724235 (View on PubMed)

Koshy SM, Geary DF. Anemia in children with chronic kidney disease. Pediatr Nephrol. 2008 Feb;23(2):209-19. doi: 10.1007/s00467-006-0381-2. Epub 2007 Jan 24.

Reference Type BACKGROUND
PMID: 17245602 (View on PubMed)

Klang B, Bjorvell H, Clyne N. Quality of life in predialytic uremic patients. Qual Life Res. 1996 Feb;5(1):109-16. doi: 10.1007/BF00435975.

Reference Type BACKGROUND
PMID: 8901373 (View on PubMed)

Gerson A, Hwang W, Fiorenza J, Barth K, Kaskel F, Weiss L, Zelikovsky N, Fivush B, Furth S. Anemia and health-related quality of life in adolescents with chronic kidney disease. Am J Kidney Dis. 2004 Dec;44(6):1017-23. doi: 10.1053/j.ajkd.2004.08.024.

Reference Type BACKGROUND
PMID: 15558522 (View on PubMed)

Mitsnefes MM, Daniels SR, Schwartz SM, Meyer RA, Khoury P, Strife CF. Severe left ventricular hypertrophy in pediatric dialysis: prevalence and predictors. Pediatr Nephrol. 2000 Sep;14(10-11):898-902. doi: 10.1007/s004670000303.

Reference Type BACKGROUND
PMID: 10975295 (View on PubMed)

Chavers BM, Herzog CA. The spectrum of cardiovascular disease in children with predialysis chronic kidney disease. Adv Chronic Kidney Dis. 2004 Jul;11(3):319-27. doi: 10.1053/j.arrt.2004.04.002.

Reference Type BACKGROUND
PMID: 15241746 (View on PubMed)

Pickett JL, Theberge DC, Brown WS, Schweitzer SU, Nissenson AR. Normalizing hematocrit in dialysis patients improves brain function. Am J Kidney Dis. 1999 Jun;33(6):1122-30. doi: 10.1016/S0272-6386(99)70150-2.

Reference Type BACKGROUND
PMID: 10352201 (View on PubMed)

Pattaragarn A, Warady BA, Sabath RJ. Exercise capacity in pediatric patients with end-stage renal disease. Perit Dial Int. 2004 May-Jun;24(3):274-80.

Reference Type BACKGROUND
PMID: 15185776 (View on PubMed)

Sietsema KE, Hiatt WR, Esler A, Adler S, Amato A, Brass EP. Clinical and demographic predictors of exercise capacity in end-stage renal disease. Am J Kidney Dis. 2002 Jan;39(1):76-85. doi: 10.1053/ajkd.2002.29884.

Reference Type BACKGROUND
PMID: 11774105 (View on PubMed)

Xia H, Ebben J, Ma JZ, Collins AJ. Hematocrit levels and hospitalization risks in hemodialysis patients. J Am Soc Nephrol. 1999 Jun;10(6):1309-16. doi: 10.1681/ASN.V1061309.

Reference Type BACKGROUND
PMID: 10361870 (View on PubMed)

Ma JZ, Ebben J, Xia H, Collins AJ. Hematocrit level and associated mortality in hemodialysis patients. J Am Soc Nephrol. 1999 Mar;10(3):610-9. doi: 10.1681/ASN.V103610.

Reference Type BACKGROUND
PMID: 10073612 (View on PubMed)

Warady BA, Ho M. Morbidity and mortality in children with anemia at initiation of dialysis. Pediatr Nephrol. 2003 Oct;18(10):1055-62. doi: 10.1007/s00467-003-1214-1. Epub 2003 Jul 23.

Reference Type BACKGROUND
PMID: 12883982 (View on PubMed)

VanDeVoorde RG, Warady BA. Management of chronic kidney disease. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N (eds). Pediatric Nephrology, 6th edn. Springer-Verlag, Berlin, 2009; 1661-92.

Reference Type BACKGROUND

Lerner G, Kale AS, Warady BA, Jabs K, Bunchman TE, Heatherington A, Olson K, Messer-Mann L, Maroni BJ. Pharmacokinetics of darbepoetin alfa in pediatric patients with chronic kidney disease. Pediatr Nephrol. 2002 Nov;17(11):933-7. doi: 10.1007/s00467-002-0932-0. Epub 2002 Sep 14.

Reference Type BACKGROUND
PMID: 12432437 (View on PubMed)

Mazahir R, Anand K, Pruthi PK. Comparison of darbepoetin alpha and recombinant human erythropoietin for treatment of anemia in pediatric chronic kidney disease: a non-inferiority trial from India. Eur J Pediatr. 2023 Jan;182(1):101-109. doi: 10.1007/s00431-022-04650-1. Epub 2022 Oct 11.

Reference Type DERIVED
PMID: 36220980 (View on PubMed)

Other Identifiers

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EC/01/18/1317

Identifier Type: -

Identifier Source: org_study_id

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