AzTrials
AzTrials

Heart Rhythm DisorderPK-AMIONCT03842020

Pharmacokinetics of Amiodarone in Children

A study testing Blood pharmacokinetic samples in people with Heart Rhythm Disorder, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages Up to 18 years
Conditions the study is for
Heart Rhythm Disorder
What is being tested?
Blood pharmacokinetic samples
Could I receive a placebo?
No, everyone receives an active treatment
How many people
57 participants
Where
1 siteFrance
Study dates
13 Feb 2019to 12 Dec 2020
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

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

Who cannot join

  • Absence of parental and / or child consent
  • Known liver dysfunction

Trial locations and contacts

1 site in 1 country.

France1 site

  • Necker Hospital

    Paris, 75015

Other trials in France

About this study

Official title: 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.

Read the 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.

Being tested
Blood pharmacokinetic samples
Keywords
heart rhythm disorder, Amiodarone, Cardiac arrhythmias, Pediatric, Population pharmacokinetic (Pop PK), Modeling
Medical subject headings
Arrhythmias, Cardiac

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Blood pharmacokinetic samplesOther

    Also called Amiodarone dosage

    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

Study groups in NCT03842020
Study groupRoleWhat they receive
Amiodarone dosageExperimentalBlood pharmacokinetics samples
Receives: Other: Blood pharmacokinetic samples

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximal Concentration (Cmax) of amiodarone

    Measured: Hour 0 to Hour 24

  2. Area under the plasma concentration versus time curve (AUC) of amiodarone

    Measured: Hour 0 to Hour 24

  3. Clearance of amiodarone

    Measured: Hour 0 to Hour 24

  4. Volume of distribution of amiodarone

    Measured: Hour 0 to Hour 24

  5. Half time of amiodarone

    Measured: Hour 0 to Hour 24

Secondary outcomes (5)

  1. Rhythm disorder

    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)

    Measured: Day 0

  2. Altered liver function

    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

    Measured: At the beginning of Amiodarone treatment until through study completion, an average of 18 months

  3. Thyroid Dysfunction

    to assess Tolerance - from blood tests or clinical follow-up : (TSH µmol/l, Free Tri-iodothyronine (FT3) and Free Thyroxine (FT4) pmol/L)

    Measured: At the beginning of Amiodarone treatment until through study completion, an average of 18 months

  4. QT and corrected QT duration

    to assess Tolerance - QT and corrected QT duration in milliseconds with an ECG

    Measured: At the beginning of Amiodarone treatment until through study completion, an average of 18 months

  5. Blood pressure : (PAS)/(PAD) (mmHg)

    to assess Tolerance

    Measured: At the beginning of Amiodarone treatment until through study completion, an average of 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Feb 2019
  2. Study start13 Feb 2019
  3. Primary completion12 Dec 2020
  4. Study completion12 Dec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
57 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03842020
Sponsor's protocol ID
APHP180299
Other IDs
2018-A02327-48
Acronym
PK-AMIO
Status last verified
Mar 2026
First submitted
4 Feb 2019
Last updated
9 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 29435949

  • 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.

    PubMed 6384328

  • 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.

    PubMed 7446409

  • 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.

    PubMed 3756044

  • 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.

    PubMed 10872646

  • 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.

    PubMed 35816412

Questions about this trial

What is this clinical trial studying?

A study testing Blood pharmacokinetic samples in people with Heart Rhythm Disorder, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximal Concentration (Cmax) of amiodarone (time frame: Hour 0 to Hour 24). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03842020, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in