Arrhythmia, Atrial Fibrillation, Atrial Flutter
Conditions
Keywords
Anti-Arrhythmia Agents, Amiodarone, chronic treatment, Amiodarone, adverse effects, Biopsy, Fine-Needle, Adipose tissue, Drug concentrations in tissues, Drug accumulation in tissues
Brief summary
The objective of this study is to determine if concentrations of amiodarone in fat tissue increases constantly over time during chronic treatment with this drug, and if blood concentrations reflect accurately the concentrations in fat tissue or not. This is because excessive concentrations of this drug in tissues can produce adverse effects.
Detailed description
Amiodarone is very effective to treat cardiac arrhythmias but its use is limited by its toxicity, specially in chronic treatment. Accumulation of the drug in tissues is very probably the cause of the majority of amiodarone delayed adverse effects. However, this has not been proved because obtaining tissue samples is usually difficult and aggressive. The investigators study, in patients following chronic treatment with amiodarone, if needle aspiration can provide samples of fat tissue useful to accurately determine amiodarone concentrations, how those concentrations in fat tissue correlate with cumulated dose, and how concentrations in fat tissue correlate with concentrations in blood, which is easier to obtain. The investigators expect this knowledge will help to understand how amiodarone develops its adverse effects and possibly lead to new ways of monitoring treatment with this drug, or to adapt doses in chronic administration.
Interventions
PROCEDUREFat tissue needle aspiration
Small fat tissue sampling performed by needle aspiration.
Sponsors
Unité de Recherches Therapeutiques - H. Lariboisiere
Hopital Lariboisière
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients taking amiodarone for more than 3 months (any dose, any indication)
Exclusion criteria
* Impossibility to perform needle aspiration of abdominal wall (local infection, skin disease) * Coagulation disorders, INR \> 3.0 if warfarin treatment * Patient unable to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relationship Between Amiodarone Concentration in Fat Tissue and Cumulated Dose. | One single measure | Correlation between amiodarone concentration in fat tissue (mean from several sampling points) and cumulated dose. |
| Relationship Between Amiodarone Concentrations in Fat Tissue and in Plasma. | One single measure, taken just before daily administration | Correlation between amiodarone concentrations in fat tissue (mean of 2 samples) and simultaneous concentration in plasma. |
| Relationship Between Amiodarone Concentrations in Fat Tissue and Developing Adverse Effects. | Cumulated time on amiodarone (varies in each patient) | Relationship between amiodarone concentrations in fat tissue (mean of two different samplings and developping adverse effects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain and Complications (if Any) Caused by Fat Tissue Needle Aspirations | 24 hours after needle aspiration | Number of patients having complications (if any) caused by fat tissue needle aspirations |
| Presence of Any Adverse Effect Attributable to Amiodarone. | Cumulated time on amiodarone (varies in each patient) | Number of patients developing adverse effects by amiodarone leading to withdrawal or specific treatment (i.e. thyroid hormone treatment) |
Countries
France
Participant flow
Recruitment details
Recruitment at a teaching hospital, from July 2006 to October 2007.
Pre-assignment details
67 consecutive patients were evaluated and 30 patients included. Reasons for non inclusion were: impossible to retrace history of amiodarone administration: 19 patients; less than 3 months on amiodarone treatment: 10 patients; unable to give informed consent: 4 patients; refused to participate: 4 patients.
Participants by arm
| Arm | Count |
|---|---|
| Amiodarone/Fat Tissue Needle Aspiration Unique arm: all patients underwent amiodarone dosage in blood and fat tissue samplings | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Amiodarone/Fat Tissue Needle Aspiration |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 24 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age Continuous | 75 years STANDARD_DEVIATION 14 |
| Region of Enrollment France | 30 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
Relationship Between Amiodarone Concentration in Fat Tissue and Cumulated Dose.
Correlation between amiodarone concentration in fat tissue (mean from several sampling points) and cumulated dose.
Time frame: One single measure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amiodarone/Fat Tissue Needle Aspiration | Relationship Between Amiodarone Concentration in Fat Tissue and Cumulated Dose. | 0.20 Correlation coefficient R |
Primary
Relationship Between Amiodarone Concentrations in Fat Tissue and Developing Adverse Effects.
Relationship between amiodarone concentrations in fat tissue (mean of two different samplings and developping adverse effects.
Time frame: Cumulated time on amiodarone (varies in each patient)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amiodarone/Fat Tissue Needle Aspiration | Relationship Between Amiodarone Concentrations in Fat Tissue and Developing Adverse Effects. | 1.01 Logistic regression OR |
Primary
Relationship Between Amiodarone Concentrations in Fat Tissue and in Plasma.
Correlation between amiodarone concentrations in fat tissue (mean of 2 samples) and simultaneous concentration in plasma.
Time frame: One single measure, taken just before daily administration
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amiodarone/Fat Tissue Needle Aspiration | Relationship Between Amiodarone Concentrations in Fat Tissue and in Plasma. | 0.68 Correlation coefficient R |
Secondary
Pain and Complications (if Any) Caused by Fat Tissue Needle Aspirations
Number of patients having complications (if any) caused by fat tissue needle aspirations
Time frame: 24 hours after needle aspiration
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amiodarone/Fat Tissue Needle Aspiration | Pain and Complications (if Any) Caused by Fat Tissue Needle Aspirations | 2 Patients |
Secondary
Presence of Any Adverse Effect Attributable to Amiodarone.
Number of patients developing adverse effects by amiodarone leading to withdrawal or specific treatment (i.e. thyroid hormone treatment)
Time frame: Cumulated time on amiodarone (varies in each patient)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amiodarone/Fat Tissue Needle Aspiration | Presence of Any Adverse Effect Attributable to Amiodarone. | 11 Patients |