Clinical trial NCT01140581: Optimal Timing of Dronedarone Initiation After Conversion in Patients With Persistent Atrial Fibrillation
Official title: A Randomized, International, Multi-center, Open-label Study to Document Optimal Timing of Initiation of Dronedarone Treatment After Conversion With Loading Dose of Amiodarone in Patients With Persistent Atrial Fibrillation Requiring Conversion of AF.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atrial Fibrillation
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-06-09
Enrollment: 402
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

- Evaluate the rate of Atrial Fibrillation (AF) recurrences one month after randomization according to different timings of initiation of dronedarone.

Secondary Objective:

* Evaluate the rate of AF recurrences two months after randomization.
* Assess the safety of the change from amiodarone to dronedarone
* Assess dronedarone safety
* Explore dronedarone and its active metabolite plasma level (in a subset of countries)
* Explore potential Pharmacokinetic (PK) interaction between dronedarone and amiodarone (in a subset of countries)


Eligibility criteria: Inclusion criteria:

Screening:

* Persistent AF for more than 72 hours (documented by an ECG taken within the last 72 hours) for whom cardioversion, anti-arrhythmic treatment and anticoagulation treatment are indicated in the opinion of the Investigator
* Naive of amiodarone treatment in the last three months
* QTc Bazett \< 500 ms on 12-lead ECG,
* At least one cardiovascular risk factor (i.e. age \> 70, hypertension, diabetes, prior cerebrovascular disease or left atrial diameter \>= 50 mm

Randomization:

* Outpatient and Inpatients (except patients hospitalized during screening period for SAE)
* Sinus rhythm
* Effective oral anticoagulation verified by International Normalized Ratio/INR (target \> 2)
* QTc Bazett \< 500 ms and PR \< 280 ms on 12-lead ECG
* Completed treatment period with amiodarone (28 days ± 2 days)

Exclusion criteria:

Screening:

* Contraindication to oral anticoagulation
* Acute condition known to cause AF
* Permanent AF
* Paroxysmal AF
* Bradycardia \< 50 bpm on the 12-lead ECG
* Clinically overt congestive heart failure:

  * with New York Heart Association (NYHA) classes III and IV heart failure
  * with LVEF \< 35%
  * or NYHA class II with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic
  * or unstable hemodynamic conditions
* Severe hepatic impairment
* Previous treatment with class I or class III anti-arrhythmic drugs (including sotalol) if taken less than one week
* Previous history of amiodarone intolerance or toxicity
* Any contraindication as per dronedarone and amiodarone labelling
* Wolff-Parkinson-White Syndrome
* Previous ablation for atrial fibrillation or any planned ablation in the next 2 months
* Contraindicated concomitant treatment:

  * Potent cytochrome P450 (CYP3A4) inhibitors
  * Use of drugs or herbal products that prolong the QT interval and known to increase the risk of Torsades de Pointes
  * Class I or III anti-arrhythmic drugs (including sotalol)

Randomization:

* Bradycardia \< 50 bpm on the 12-lead ECG
* Clinically overt congestive heart failure:

  * with New York Heart Association (NYHA) classes III and IV heart failure
  * with LVEF \< 35%
  * or NYHA class II with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic
  * or unstable hemodynamic conditions
* Severe hepatic impairment
* Previous treatment with class I or class III anti-arrhythmic drugs (including sotalol) if taken less than one week
* Patient in whom the following contraindicated concomitant treatment is mandatory:

  * Potent cytochrome P450 (CYP3A4) inhibitors
  * Use of drugs or herbal products that prolong the QT interval and known to increase the risk of Torsades de Pointes
  * Class I or III anti-arrhythmic drugs (including sotalol)

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: AF recurrences
timeFrame: one month after randomization
Secondary outcomes:
measure: AF recurrences
timeFrame: two months after randomization
measure: Symptomatic bradycardia
timeFrame: two months after randomization
measure: Tachycardia
timeFrame: two months after randomization
measure: Dronedarone and amiodarone concentrations in plasma
timeFrame: 3 hours, 1 week, 2 weeks and 4 weeks after 1st Dronedarone intake
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Investigational Site Number 009
city: Ballarat
country: Australia
facility: Investigational Site Number 013
city: Garran
country: Australia
facility: Investigational Site Number 002
city: Herston
country: Australia
facility: Investigational Site Number 007
city: Hobart
country: Australia
facility: Investigational Site Number 012
city: Liverpool
country: Australia
facility: Investigational Site Number 006
city: Maroubra
country: Australia
facility: Investigational Site Number 010
city: Nedlands
country: Australia
facility: Investigational Site Number 001
city: New Lambton
country: Australia
facility: Investigational Site Number 004
city: Redcliffe
country: Australia
facility: Investigational Site Number 008
city: South Brisbane
country: Australia
facility: Investigational Site Number 011
city: Southport
country: Australia
facility: Investigational Site Number 005
city: Woolloongabba
country: Australia
facility: Investigational Site Number 003
city: Braunau
country: Austria
facility: Investigational Site Number 040-006
city: Innsbruck
country: Austria
facility: Investigational Site Number 040-007
city: Linz
country: Austria
facility: Investigational Site Number 040-002
city: Mödling
country: Austria
facility: Investigational Site Number 040-001
city: Vienna
country: Austria
facility: Investigational Site Number 040-003
city: Wien
country: Austria
facility: Investigational Site Number 040-005
city: Wien
country: Austria
facility: Investigational Site Number 040-004
city: Tallinn
country: Estonia
facility: Investigational Site Number 233001
city: Hyvinkää
country: Finland
facility: Investigational Site Number 246-001
city: Hyvinkää
country: Finland
facility: Investigational Site Number 246-002
city: Pori
country: Finland
facility: Investigational Site Number 246-004
city: Seinäjoki
country: Finland
facility: Investigational Site Number 246-003
city: Avignon Cedex 9
country: France
facility: Investigational Site Number 250-006
city: BEZIERS Cedex
country: France
facility: Investigational Site Number 250-009
city: Bron
country: France
facility: Investigational Site Number 250-002
city: Cholet
country: France
facility: Investigational Site Number 250-007
city: Lyon Cedex 03
country: France
facility: Investigational Site Number 250-008
city: NIMES Cedex 9
country: France
facility: Investigational Site Number 250-010
city: POITIERS Cedex
country: France
facility: Investigational Site Number 250-003
city: Toulouse Cedex 3
country: France
facility: Investigational Site Number 250-004
city: Valence Cedex 9
country: France
facility: Investigational Site Number 250-005
city: Vandoeuvre Les Nancy
country: France
facility: Investigational Site Number 250-001
city: Berlin
country: Germany
facility: Investigational Site Number 276-003
city: Bernau
country: Germany
facility: Investigational Site Number 276-006
city: Bonn
country: Germany
facility: Investigational Site Number 276-001
city: Dresden
country: Germany
facility: Investigational Site Number 276-011
city: Frankfurt am Main
country: Germany
facility: Investigational Site Number 276-010
city: Hamburg
country: Germany
facility: Investigational Site Number 276-002
city: Hamburg
country: Germany
facility: Investigational Site Number 276-008
city: Heidenau
country: Germany
facility: Investigational Site Number 276-009
city: Kiel
country: Germany
facility: Investigational Site Number 276-004
city: Ludwigsburg
country: Germany
facility: Investigational Site Number 276-005
city: Paderborn
country: Germany
facility: Investigational Site Number 276-007
city: Ashkelon
country: Israel
facility: Investigational Site Number 376002
city: Beer Yaakov
country: Israel
facility: Investigational Site Number 376001
city: Ancona
country: Italy
facility: Investigational Site Number 380-005
city: Barga
country: Italy
facility: Investigational Site Number 380-002
city: Catania
country: Italy
facility: Investigational Site Number 380-004
city: Como
country: Italy
facility: Investigational Site Number 380-001
city: Cortona
country: Italy
facility: Investigational Site Number 380-006
city: Mestre
country: Italy
facility: Investigational Site Number 380-011
city: Palermo
country: Italy
facility: Investigational Site Number 380-010
city: Roma
country: Italy
facility: Investigational Site Number 380-007
city: Roma
country: Italy
facility: Investigational Site Number 380-003
city: San Daniele Del Friuli
country: Italy
facility: Investigational Site Number 380-009
city: Varese
country: Italy
facility: Investigational Site Number 380-012
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410001
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410002
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410003
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410004
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410005
city: Suwon
country: Korea, Republic of
facility: Investigational Site Number 410006
city: Aguascalientes
country: Mexico
facility: Investigational Site Number 484017
city: Chihuahua
country: Mexico
facility: Investigational Site Number 484012
city: Guadalajara
country: Mexico
facility: Investigational Site Number 484008
city: Guadalajara
country: Mexico
facility: Investigational Site Number 484009
city: Guadalajara
country: Mexico
facility: Investigational Site Number 484015
city: Leon
country: Mexico
facility: Investigational Site Number 484002
city: Mexico
country: Mexico
facility: Investigational Site Number 484016
city: Mexico
country: Mexico
facility: Investigational Site Number 484004
city: Monterrey
country: Mexico
facility: Investigational Site Number 484005
city: Monterrey
country: Mexico
facility: Investigational Site Number 484003
city: Queretaro
country: Mexico
facility: Investigational Site Number 484001
city: Saltillo
country: Mexico
facility: Investigational Site Number 484013
city: Tijuana
country: Mexico
facility: Investigational Site Number 484011
city: Amsterdam
country: Netherlands
facility: Investigational Site Number 528003
city: Goes
country: Netherlands
facility: Investigational Site Number 528005
city: Groningen
country: Netherlands
facility: Investigational Site Number 528002
city: Maastricht
country: Netherlands
facility: Investigational Site Number 528001
city: Rotterdam
country: Netherlands
facility: Investigational Site Number 528004
city: Amadora
country: Portugal
facility: Investigational Site Number 620005
city: Lisboa
country: Portugal
facility: Investigational Site Number 620001
city: El Palmar (MURCIA)
country: Spain
facility: Investigational Site Number 724004
city: Hospitalet de Llobregat
country: Spain
facility: Investigational Site Number 724005
city: La Coruña
country: Spain
facility: Investigational Site Number 724008
city: LLeida
country: Spain
facility: Investigational Site Number 724003
city: Madrid
country: Spain
facility: Investigational Site Number 724010
city: Madrid
country: Spain
facility: Investigational Site Number 724001
city: Majadahonda
country: Spain
facility: Investigational Site Number 724002
city: Sevilla
country: Spain
facility: Investigational Site Number 724006
city: Tarragona
country: Spain
facility: Investigational Site Number 724007
city: Valencia
country: Spain
facility: Investigational Site Number 724009
city: Basel
country: Switzerland
facility: Investigational Site Number 756001
city: St.Gallen
country: Switzerland
facility: Investigational Site Number 756002
city: Kaohsiung Hsien,
country: Taiwan
facility: Investigational Site Number 158005
city: Kaohsiung
country: Taiwan
facility: Investigational Site Number 158006
city: Taichung City
country: Taiwan
facility: Investigational Site Number 158009
city: Taichung
country: Taiwan
facility: Investigational Site Number 158004
city: Taichung
country: Taiwan
facility: Investigational Site Number 158003
city: Taipei
country: Taiwan
facility: Investigational Site Number 158002
city: Taipei
country: Taiwan
facility: Investigational Site Number 158001
city: Taipei
country: Taiwan
facility: Investigational Site Number 158008
city: Tao Yuan Hsien
country: Taiwan
facility: Investigational Site Number 158007
city: Belfast
country: United Kingdom
facility: Investigational Site Number 826006
city: Bournemouth
country: United Kingdom
facility: Investigational Site Number 826-005
city: Carshalton
country: United Kingdom
facility: Investigational Site Number 826-001
city: Gloucester
country: United Kingdom
facility: Investigational Site Number 826-002
city: Wrexham
country: United Kingdom
facility: Investigational Site Number 826-007
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Naccarelli GV, Bhatt DL, Camm AJ, Le Heuzey JY, Lombardi F, Tamargo J, Martinez JM, Naditch-Brule L; ARTEMIS AF Investigators. Evaluation of the Switch From Amiodarone to Dronedarone in Patients With Atrial Fibrillation: Results of the ARTEMIS AF Studies. J Cardiovasc Pharmacol Ther. 2020 Sep;25(5):425-437. doi: 10.1177/1074248420926874. Epub 2020 Jun 5.