Optimal Timing of Dronedarone Initiation After Conversion in Patients With Persistent Atrial Fibrillation

Atrial Fibrillation Clinical Trial

— ARTEMIS Load  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01140581
• Other study ID #: DRONE_C_03668
• Secondary ID: 2009-016818-24
• Status: Completed
• Phase: Phase 4
• First received: June 8, 2010
• Last updated: January 20, 2012
• Start date: September 2010
• Est. completion date: December 2011

Study information

• Verified date: January 2012
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 402
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• DRONEDARONE
Pharmaceutical form: tablet Route of administration: oral Dose regimen: 400 mg

Locations

Country	Name	City	State
Australia	Investigational Site Number 009	Adelaide
Australia	Investigational Site Number 013	Ballarat
Australia	Investigational Site Number 002	Garran
Australia	Investigational Site Number 007	Herston
Australia	Investigational Site Number 012	Hobart
Australia	Investigational Site Number 006	Liverpool
Australia	Investigational Site Number 010	Maroubra
Australia	Investigational Site Number 001	Nedlands
Australia	Investigational Site Number 004	New Lambton
Australia	Investigational Site Number 008	Redcliffe
Australia	Investigational Site Number 011	South Brisbane
Australia	Investigational Site Number 005	Southport
Australia	Investigational Site Number 003	Woolloongabba
Austria	Investigational Site Number 040-006	Braunau
Austria	Investigational Site Number 040-007	Innsbruck
Austria	Investigational Site Number 040-002	Linz
Austria	Investigational Site Number 040-001	Mödling
Austria	Investigational Site Number 040-003	Vienna
Austria	Investigational Site Number 040-004	Wien
Austria	Investigational Site Number 040-005	Wien
Estonia	Investigational Site Number 233001	Tallinn
Finland	Investigational Site Number 246-001	Hyvinkää
Finland	Investigational Site Number 246-002	Hyvinkää
Finland	Investigational Site Number 246-004	Pori
Finland	Investigational Site Number 246-003	Seinäjoki
France	Investigational Site Number 250-006	Avignon Cedex 9
France	Investigational Site Number 250-009	BEZIERS Cedex
France	Investigational Site Number 250-002	Bron
France	Investigational Site Number 250-007	Cholet
France	Investigational Site Number 250-008	Lyon Cedex 03
France	Investigational Site Number 250-010	NIMES Cedex 9
France	Investigational Site Number 250-003	POITIERS Cedex
France	Investigational Site Number 250-004	Toulouse Cedex 3
France	Investigational Site Number 250-005	Valence Cedex 9
France	Investigational Site Number 250-001	Vandoeuvre Les Nancy
Germany	Investigational Site Number 276-003	Berlin
Germany	Investigational Site Number 276-006	Bernau
Germany	Investigational Site Number 276-001	Bonn
Germany	Investigational Site Number 276-011	Dresden
Germany	Investigational Site Number 276-010	Frankfurt am Main
Germany	Investigational Site Number 276-002	Hamburg
Germany	Investigational Site Number 276-008	Hamburg
Germany	Investigational Site Number 276-009	Heidenau
Germany	Investigational Site Number 276-004	Kiel
Germany	Investigational Site Number 276-005	Ludwigsburg
Germany	Investigational Site Number 276-007	Paderborn
Israel	Investigational Site Number 376002	Ashkelon
Israel	Investigational Site Number 376001	Beer Yaakov
Italy	Investigational Site Number 380-005	Ancona
Italy	Investigational Site Number 380-002	Barga
Italy	Investigational Site Number 380-004	Catania
Italy	Investigational Site Number 380-001	Como
Italy	Investigational Site Number 380-006	Cortona
Italy	Investigational Site Number 380-011	Mestre
Italy	Investigational Site Number 380-010	Palermo
Italy	Investigational Site Number 380-003	Roma
Italy	Investigational Site Number 380-007	Roma
Italy	Investigational Site Number 380-009	San Daniele Del Friuli
Italy	Investigational Site Number 380-012	Varese
Korea, Republic of	Investigational Site Number 410001	Seoul
Korea, Republic of	Investigational Site Number 410002	Seoul
Korea, Republic of	Investigational Site Number 410003	Seoul
Korea, Republic of	Investigational Site Number 410004	Seoul
Korea, Republic of	Investigational Site Number 410005	Seoul
Korea, Republic of	Investigational Site Number 410006	Suwon
Mexico	Investigational Site Number 484017	Aguascalientes
Mexico	Investigational Site Number 484012	Chihuahua
Mexico	Investigational Site Number 484008	Guadalajara
Mexico	Investigational Site Number 484009	Guadalajara
Mexico	Investigational Site Number 484015	Guadalajara
Mexico	Investigational Site Number 484002	Leon
Mexico	Investigational Site Number 484004	Mexico
Mexico	Investigational Site Number 484016	Mexico
Mexico	Investigational Site Number 484003	Monterrey
Mexico	Investigational Site Number 484005	Monterrey
Mexico	Investigational Site Number 484001	Queretaro
Mexico	Investigational Site Number 484013	Saltillo
Mexico	Investigational Site Number 484011	Tijuana
Netherlands	Investigational Site Number 528003	Amsterdam
Netherlands	Investigational Site Number 528005	Goes
Netherlands	Investigational Site Number 528002	Groningen
Netherlands	Investigational Site Number 528001	Maastricht
Netherlands	Investigational Site Number 528004	Rotterdam
Portugal	Investigational Site Number 620005	Amadora
Portugal	Investigational Site Number 620001	Lisboa
Spain	Investigational Site Number 724004	El Palmar (MURCIA)
Spain	Investigational Site Number 724005	Hospitalet de Llobregat
Spain	Investigational Site Number 724008	La Coruña
Spain	Investigational Site Number 724003	LLeida
Spain	Investigational Site Number 724001	Madrid
Spain	Investigational Site Number 724010	Madrid
Spain	Investigational Site Number 724002	Majadahonda
Spain	Investigational Site Number 724006	Sevilla
Spain	Investigational Site Number 724007	Tarragona
Spain	Investigational Site Number 724009	Valencia
Switzerland	Investigational Site Number 756001	Basel
Switzerland	Investigational Site Number 756002	St.Gallen
Taiwan	Investigational Site Number 158006	Kaohsiung
Taiwan	Investigational Site Number 158005	Kaohsiung Hsien,
Taiwan	Investigational Site Number 158003	Taichung
Taiwan	Investigational Site Number 158004	Taichung
Taiwan	Investigational Site Number 158009	Taichung City
Taiwan	Investigational Site Number 158001	Taipei
Taiwan	Investigational Site Number 158002	Taipei
Taiwan	Investigational Site Number 158008	Taipei
Taiwan	Investigational Site Number 158007	Tao Yuan Hsien
United Kingdom	Investigational Site Number 826006	Belfast
United Kingdom	Investigational Site Number 826-005	Bournemouth
United Kingdom	Investigational Site Number 826-001	Carshalton
United Kingdom	Investigational Site Number 826-002	Gloucester
United Kingdom	Investigational Site Number 826-007	Wrexham

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

Australia,  Austria,  Estonia,  Finland,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Portugal,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AF recurrences	two consecutives 12-lead ECG or Trans-Telephonic ECG monitoring (TTEM) approximatively 10 minutes apart and both showing AF	one month after randomization	No
Secondary	AF recurrences		two months after randomization	No
Secondary	Symptomatic bradycardia	Heart rate at rest < 50 beats per minute	two months after randomization	No
Secondary	Tachycardia	Heart rate at rest > 120 beats per minute	two months after randomization	No
Secondary	Dronedarone and amiodarone concentrations in plasma	Limited to a subset of countries	3 hours, 1 week, 2 weeks and 4 weeks after 1st Dronedarone intake	No