Pharmacokinetics of Amiodarone in Children

NCT ID: NCT03842020

Last Updated: 2025-08-28

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

NA

Total Enrollment

57 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-13

Study Completion Date

2020-12-12

Brief Summary

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PK-AMIO study is a population pharmacokinetic study of Amiodarone in children in order to :

* study the pharmacokinetic parameters (Pop PK) of Amiodarone in children;
* identify covariates explaining the variability of these pharmacokinetic parameters;
* study the relationship between the concentration, the efficacy of treatment and its tolerance to optimize the use of Amiodarone in pediatrics.

Indeed, there is no consensus on the optimal oral dosage in children. Few pharmacokinetic studies have been performed with only a small number of patients per study. Our study will include 70 children aged 0 to 18 years old.

Detailed Description

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The incidence of supraventricular rhythm disorders in children is 1/250 to 1/1000. Amiodarone is used until the age of 1 year to limit the risk of recurrence. Efficiency is around 60% with no predictive factors identified. According to the study by Dallefeld (2018), unexplained inter-individual variability in pharmacokinetic parameters is 200%. Its adverse effects are numerous and affect 10% of patients. The concentration-effect relationship is poorly known. Amiodarone can cause hypotension and bradycardia. Liver and thyroid function should be monitored as well. Amiodarone is metabolised by cytochromes, mainly CYP3A4. Drug interactions and cytochrome variation in the neonatal period may alter its elimination kinetics. Pharmacokinetic studies have been conducted in adults with target concentrations of 0.5 to 2.5 mg/l.

The efficacy of oral amiodarone in children has been shown in studies in 1980; however, there is no consensus on optimal dosage. Despite its widespread use in children, few pharmacokinetic studies have been conducted in a small number of patients at different doses. The population pharmacokinetics and pharmacodynamics of Amiodarone in children, as well as its general and scientific interest, will be studied in this study. The lack of efficacy and the occurrence of adverse events of Amiodarone in children may be related to the large inter-individual pharmacokinetic variability.

Currently, more than 200 children treated with Amiodarone are being followed at Necker-Enfants malades Hospital.

This prospective study will be conducted in three paediatric services of Necker-Enfants malades Hospital in Paris, France.

Patient selection will take place in the 3 paediatric services. The senior physician proposes the study to holders of parental authority whose child receives or will receive the treatment during its follow-up or hospitalization.

After verification of the inclusion and exclusion criteria, the consent of the parents or parental authority and the child, according to his age, will be obtained.

After agreement, and/or signature of the parents and the non-oral opposition of the child in age to understand the information, the child is sampled according to the following scheme:

* The samples taken during the introduction of the treatment in hospital will be made to observe the pharmacokinetics at the first dose: 3 samples will be taken in the following time windows: \[H0-H3\]; \[H5-H9\] and just before the next dose administration (H24).
* During the maintenance treatment, a sample will be taken during a scheduled consultation or during a hospitalization.
* Blood PK samples will be drawn until 1 month after end of treatment.

All patients' samples will be kept for to be analyzed at the Pharmacology department of the Cochin hospital.

No intervention or no charge will be made for this study.

This population pharmacokinetic study in children aims to analyze the concentration-effectiveness and concentration-tolerance relationship to optimize its use.

Conditions

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Heart Rhythm Disorder

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Amiodarone dosage

Blood pharmacokinetics samples

Group Type EXPERIMENTAL

Blood pharmacokinetic samples

Intervention Type OTHER

1 or 3 sample(s) will be taken in the following time windows: \[H0-H3\]; \[H5-H9\] and just before the next set \[H24\], depending if the child is or is not admitted to hospital

Interventions

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Blood pharmacokinetic samples

1 or 3 sample(s) will be taken in the following time windows: \[H0-H3\]; \[H5-H9\] and just before the next set \[H24\], depending if the child is or is not admitted to hospital

Intervention Type OTHER

Other Intervention Names

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Amiodarone dosage

Eligibility Criteria

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Inclusion Criteria

* All children from 0 to 18 years old treated with Amiodarone for any rhythm disorder, and followed to Necker-Enfants maladies hospital.

Exclusion Criteria

* Absence of parental and / or child consent
* Known liver dysfunction
Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean-Marc TRELUYER, MD, PhD

Role: STUDY_DIRECTOR

Assistance Publique - Hôpitaux de Paris

Damien BONNET, MD, PhD

Role: STUDY_DIRECTOR

Assistance Publique - Hôpitaux de Paris

Sylvain RENOLLEAU, MD, PhD

Role: STUDY_DIRECTOR

Assistance Publique - Hôpitaux de Paris

Amelia LEHNERT, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

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Necker Hospital

Paris, , France

Site Status

Countries

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France

References

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Lehnert A, Foissac F, Bouazza N, Urien S, Oualha M, Renolleau S, Barbanti C, Di Marzio A, Bonnet D, Abdalla S, Zheng Y, Treluyer JM. Amiodarone/N-desethylamiodarone population pharmacokinetics in paediatric patients. Br J Clin Pharmacol. 2022 Dec;88(12):5369-5377. doi: 10.1111/bcp.15458. Epub 2022 Jul 29.

Reference Type BACKGROUND
PMID: 35816412 (View on PubMed)

Dallefeld SH, Atz AM, Yogev R, Sullivan JE, Al-Uzri A, Mendley SR, Laughon M, Hornik CP, Melloni C, Harper B, Lewandowski A, Mitchell J, Wu H, Green TP, Cohen-Wolkowiez M. A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):419-430. doi: 10.1007/s10928-018-9576-y. Epub 2018 Feb 12.

Reference Type BACKGROUND
PMID: 29435949 (View on PubMed)

Garson A Jr, Gillette PC, McVey P, Hesslein PS, Porter CJ, Angell LK, Kaldis LC, Hittner HM. Amiodarone treatment of critical arrhythmias in children and young adults. J Am Coll Cardiol. 1984 Oct;4(4):749-55. doi: 10.1016/s0735-1097(84)80402-7.

Reference Type BACKGROUND
PMID: 6384328 (View on PubMed)

Coumel P, Fidelle J. Amiodarone in the treatment of cardiac arrhythmias in children: one hundred thirty-five cases. Am Heart J. 1980 Dec;100(6 Pt 2):1063-9. doi: 10.1016/0002-8703(80)90214-8.

Reference Type BACKGROUND
PMID: 7446409 (View on PubMed)

Bucknall CA, Keeton BR, Curry PV, Tynan MJ, Sutherland GR, Holt DW. Intravenous and oral amiodarone for arrhythmias in children. Br Heart J. 1986 Sep;56(3):278-84. doi: 10.1136/hrt.56.3.278.

Reference Type BACKGROUND
PMID: 3756044 (View on PubMed)

Pollak PT, Bouillon T, Shafer SL. Population pharmacokinetics of long-term oral amiodarone therapy. Clin Pharmacol Ther. 2000 Jun;67(6):642-52. doi: 10.1067/mcp.2000.107047.

Reference Type BACKGROUND
PMID: 10872646 (View on PubMed)

Other Identifiers

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2018-A02327-48

Identifier Type: REGISTRY

Identifier Source: secondary_id

APHP180299

Identifier Type: -

Identifier Source: org_study_id

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