Non-inferiority of liquid thyroxine in comparison to tablets formulation in the treatment of children with congenital hypothyroidism

Flora Tzifi; Alexandra Iliadi; Antonis Voutetakis; Dimitris Platis; Panagiotis Girginoudis; Christina Kanaka-Gantenbein

doi:10.1515/jpem-2021-0458

Article

Non-inferiority of liquid thyroxine in comparison to tablets formulation in the treatment of children with congenital hypothyroidism

Flora Tzifi , Alexandra Iliadi , Antonis Voutetakis , Dimitris Platis , Panagiotis Girginoudis and Christina Kanaka-Gantenbein

Published/Copyright: October 18, 2021

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 35 Issue 2

Abstract

Objectives

The aim of the current prospective randomized control study was to assess efficacy, safety, and non-inferiority of a new liquid L-thyroxine formulation dissolved in glycerol and water (T4^® drops, produced by a Greek pharmaceutical Company, Uni-Pharma, Athens, Greece) in comparison to the standard Tablets form (T4^® tablets, Uni-Pharma, Athens, Greece) in the substitutive treatment of children with congenital hypothyroidism (CH).

Methods

Thirty-nine children with CH, aged 3–12 years old, were enrolled in the study, after parental Informed Consent has been obtained, while three patients were lost from follow-up. At baseline, all participants had normal thyroid-stimulating hormone (TSH) and Free T4 values. Patients were randomly subdivided according to the assigned treatment in Group A (n=17)-Tablet Form and Group B (n=19)-Liquid Form. TSH and Free T4 levels were evaluated at 0, 2, 4, and 6 months.

Results

TSH values showed a statistically significant difference (p=0.017) between groups only at six months (Group A having higher TSH levels than Group B, albeit within the normal range), while Free T4 levels had no statistical difference throughout the six month study period and were always within the normal range. Moreover, dose adjustments were more frequent in Group A (p=0.038) during the six months. Liquid L-thyroxine substitutive treatment exhibited no statistically significant adverse effects in comparison to the widely used tablets.

Conclusions

Levothyroxine (LT4) as liquid solution formulation is safe and noninferior to the widely used L-thyroxine Tablets, with less need for dose adjustment, and can therefore be safely used in the treatment of children with CH.

Keywords: children; congenital hypothyroidism (CH); levothyroxine (LT4); liquid thyroxine; tablets

Corresponding author: Flora Tzifi, MD, MSc, PhD, Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics Medical School, National and Kapodistrian University of Athens, “Aghia Sophia” Children’s Hospital, Papadiamantopoulou and Thivon 1, 115-27, Athens, Greece, Phone: +306944536237, E-mail: fl_tzifi@hotmail.com

Flora Tzifi and Alexandra Iliadi contributed equally to this work.

Funding source: Uni-Pharma

Funding source: Uni-Pharma None

Award Identifier / Grant number: EudraCT 2013-002139-15

Acknowledgments

We thank Mrs. Anna Gkika, a laboratory technician at the ICH, who performed the blood sampling for the hormonal assessments, as well as all patients and their parents for their willingness to participate in the study.

Research funding: Pharmaceutical company Uni-Pharma contributed financially to the current study, by providing levothyroxine liquid and tablets, covering expenses for patient’s transportation, in laboratory kits for TSH and fT4 measurements, but had no interference with data analysis or manuscript writing. The study was funded by the Uni-Pharma, EudraCT Number 2013-002139-15.
Author contributions: Dr F.T contributed to the study design and was responsible for clinical examination and follow-up of patients. She was also responsible for data collection, data analysis, literature search, and manuscript writing. Dr A.I contributed to the study design, patients’ recruitment and enrollment, sample and data collection, data analysis, data interpretation, literature search, and writing the manuscript. Dr A.V contributed to the study design and was responsible for clinical examination and follow-up of patients. Dr P.G and Dr D.P were responsible for patient screening and laboratory sample analysis. Professor CKG supervised the design and execution of the study and contributed to the writing and editing of the manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: All authors declare that they have no conflict of interest.
Ethical approval: The study was approved by the local Ethics Committee of the Agia Sophia Children’s Hospital and has been registered as EudraCT Number 2013-002139-15 by the National Drugs Organization. The study has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

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Received: 2021-07-06

Accepted: 2021-09-27

Published Online: 2021-10-18

Published in Print: 2022-02-23

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Articles in the same Issue

https://doi.org/10.1515/jpem-2021-0458

Keywords for this article

children; congenital hypothyroidism (CH); levothyroxine (LT4); liquid thyroxine; tablets