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

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A Correction to this article was published on 20 October 2022

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Abstract

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.

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Availability of data and materials

All data generated or analyzed during this study are included in this published article and are also available from the corresponding author on reasonable request.

Code availability

Not applicable.

Change history

Abbreviations

ANCOVA:

Analysis of covariance

CKD:

Chronic kidney disease

CI:

Confidence interval

DA:

Darbepoetin alpha

DBP:

Diastolic blood pressures

EPO:

Erythropoietin

ESAs:

Erythropoiesis stimulating agents

ESKD:

End stage kidney disease

GFR:

Glomerular filtration rate

Hb:

Hemoglobin

INR:

Indian rupee

ITT:

Intent to treat

KDIGO:

Kidney Disease Improving Global Outcomes

PP:

Per protocol

QW:

Once weekly

Q2W:

Every two weeks

rHuEPO:

Recombinant human erythropoietin

RBC:

Red blood cells

SBP:

Systolic blood pressures

SD:

Standard deviation

Tsat:

Transferrin saturation

USD:

US dollar

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Author information

Authors and Affiliations

  1. Department of Pediatrics, Teerthanker Mahaveer Medical College and Research Centre, TMU, Uttar Pradesh, Moradabad, India

    Rufaida Mazahir

  2. Division of Pediatric Nephrology, Department of Pediatrics, Institute of Child Health, Sir Ganga Ram Hospital, New Delhi, India

    Rufaida Mazahir, Kanav Anand & P. K. Pruthi

Authors
  1. Rufaida Mazahir
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  3. P. K. Pruthi
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Contributions

All the authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Rufaida Mazahir, Kanav Anand and PK Pruthi. The first draft of the manuscript was written by Rufaida Mazahir, and all the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Rufaida Mazahir.

Ethics declarations

Ethics approval

This research involved human participants. All procedures performed in the current study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by Ethics committee, Sir Ganga Ram Hospital, New Delhi, India (Date: 20/01/2018; No-EC/01/18/1317).

Consent to participate

Written informed consent was obtained from the parents/legal guardians. For children older than 7 years, assent was also obtained.

Consent for publication

Parents/legal guardians signed informed consent regarding publishing their data.

Competing interests

The authors declare no competing interests.

Additional information

Communicated by Peter de Winter

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The abstract of the study has been accepted for oral presentation at the upcoming 19th Congress of the International Pediatric Nephrology Association to be held on 7th–11th September 2022, Calgary, Canada.

The original online version of this article was revised: Missing minus symbol in Table 4 has been added.

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Mazahir, R., Anand, K. & Pruthi, P.K. 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 182, 101–109 (2023). https://doi.org/10.1007/s00431-022-04650-1

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