Pharmacokinetics of Amiodarone in Children (PK-AMIO)

March 19, 2021 updated by: Assistance Publique - Hôpitaux de Paris

Population Pharmacokinetics and Pharmacodynamics of Amiodarone in Children": PK-AMIO

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

57

Phase

  • Not Applicable

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

  • France
      • Paris, France, 75015
        • Necker 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

No older than 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Amiodarone dosage
Blood pharmacokinetics samples
Other: 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
Other Names:
  • Amiodarone dosage

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximal Concentration (Cmax) of amiodarone
Time Frame: Hour 0 to Hour 24
Hour 0 to Hour 24
Area under the plasma concentration versus time curve (AUC) of amiodarone
Time Frame: Hour 0 to Hour 24
Hour 0 to Hour 24
Clearance of amiodarone
Time Frame: Hour 0 to Hour 24
Hour 0 to Hour 24
Volume of distribution of amiodarone
Time Frame: Hour 0 to Hour 24
Hour 0 to Hour 24
Half time of amiodarone
Time Frame: Hour 0 to Hour 24
Hour 0 to Hour 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rhythm disorder
Time Frame: Day 0
to assess Efficacity - Detection of the rhythm disorder on an ECG or scope (during hospitalization or consultation), or an ECG holter: absence of rhythm disorders at the atrial, junctional or ventricular level Or oral report from parents of rhythm disorder between 2 consultations (palpitation, heart rate acceleration)
Day 0
Altered liver function
Time Frame: At the beginning of Amiodarone treatment until through study completion, an average of 18 months
to assess Tolerance - from blood tests or clinical follow-up : gammaglutamyl transferase (GGT) U/L , Alkaline Phosphatase (ALP) U/L, Alanine Transaminase (ALT) U/L Aspartate Transaminase (AST) U/L,Total / conjugated/ free bilirubin µmol/L
At the beginning of Amiodarone treatment until through study completion, an average of 18 months
Thyroid Dysfunction
Time Frame: At the beginning of Amiodarone treatment until through study completion, an average of 18 months
to assess Tolerance - from blood tests or clinical follow-up : (TSH µmol/l, Free Tri-iodothyronine (FT3) and Free Thyroxine (FT4) pmol/L)
At the beginning of Amiodarone treatment until through study completion, an average of 18 months
QT and corrected QT duration
Time Frame: At the beginning of Amiodarone treatment until through study completion, an average of 18 months
to assess Tolerance - QT and corrected QT duration in milliseconds with an ECG
At the beginning of Amiodarone treatment until through study completion, an average of 18 months
Blood pressure : (PAS)/(PAD) (mmHg)
Time Frame: At the beginning of Amiodarone treatment until through study completion, an average of 18 months
to assess Tolerance
At the beginning of Amiodarone treatment until through study completion, an average of 18 months

Collaborators and Investigators

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

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

URC-CIC Paris Descartes Necker Cochin

Investigators

  • Study Director: Jean-Marc Tréluyer, MD, PhD, Assistance Publique - Hôpitaux de Paris
  • Study Director: Damien BONNET, MD, PhD, Assistance Publique - Hôpitaux de Paris
  • Study Director: Sylvain RENOLLEAU, MD, PhD, Assistance Publique - Hôpitaux de Paris
  • Principal Investigator: Amelia LEHNERT, MD, PhD, Assistance Publique - Hôpitaux de Paris

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 13, 2019

Primary Completion (Actual)

December 12, 2020

Study Completion (Actual)

December 12, 2020

Study Registration Dates

First Submitted

February 4, 2019

First Submitted That Met QC Criteria

February 12, 2019

First Posted (Actual)

February 15, 2019

Study Record Updates

Last Update Posted (Actual)

March 22, 2021

Last Update Submitted That Met QC Criteria

March 19, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP180299
  • 2018-A02327-48 (Registry Identifier: ID-RCB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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