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

NCT01140581 | Completed Phase 4 DMC

• 2 other identifiers: DRONE_C_036682009-016818-24
• Study Type: interventional
• Target: 402
• Locations: 14 countries
• Sites: 94

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)

Conditions

Atrial Fibrillation

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• AF recurrences

  two months after randomization

• Symptomatic bradycardia

  two months after randomization

• Tachycardia

  two months after randomization

• Dronedarone and amiodarone concentrations in plasma

  3 hours, 1 week, 2 weeks and 4 weeks after 1st Dronedarone intake

Study Arms (3)

Group A

EXPERIMENTAL

Amiodarone 600 mg daily for 1 week then 400 mg daily for 1 week then 200 mg daily for 2 weeks followed by dronedarone 400 mg twice daily for 8 weeks

Drug: DRONEDARONE

Group B

EXPERIMENTAL

Amiodarone 600 mg daily for 1 week then 400 mg daily for 1 week then 200 mg daily for 2 weeks. Two weeks wash-out followed by dronedarone 400 mg twice daily for 6 weeks

Drug: DRONEDARONE

Group C

EXPERIMENTAL

Amiodarone 600 mg daily for 1 week then 400 mg daily for 1 week then 200 mg daily for 2 weeks. Four weeks wash-out followed by dronedarone 400 mg twice daily for 4 weeks

Drug: DRONEDARONE

Interventions

DRONEDARONE DRUG

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

Group A; Group B; Group C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Sanofi: lead

Study Sites (111)

Investigational Site Number 009

Adelaide, 5000, Australia

Location

Investigational Site Number 013

Ballarat, 3350, Australia

Location

Investigational Site Number 002

Garran, 2605, Australia

Location

Investigational Site Number 007

Herston, 4006, Australia

Location

Investigational Site Number 012

Hobart, 7000, Australia

Location

Investigational Site Number 006

Liverpool, 2170, Australia

Location

Investigational Site Number 010

Maroubra, 2035, Australia

Location

Investigational Site Number 001

Nedlands, 6009, Australia

Location

Investigational Site Number 004

New Lambton, 2305, Australia

Location

Investigational Site Number 008

Redcliffe, 4020, Australia

Location

Investigational Site Number 011

South Brisbane, 4101, Australia

Location

Investigational Site Number 005

Southport, 4215, Australia

Location

Investigational Site Number 003

Woolloongabba, 4102, Australia

Location

Investigational Site Number 040-006

Braunau am Inn, 5280, Austria

Location

Investigational Site Number 040-007

Innsbruck, 6020, Austria

Location

Investigational Site Number 040-002

Linz, 4010, Austria

Location

Investigational Site Number 040-001

Mödling, 2340, Austria

Location

Investigational Site Number 040-005

Vienna, 1090, Austria

Location

Investigational Site Number 040-003

Vienna, Austria

Location

Investigational Site Number 040-004

Vienna, Austria

Location

Investigational Site Number 233001

Tallinn, 10138, Estonia

Location

Investigational Site Number 246-001

Hyvinkää, 05850, Finland

Location

Investigational Site Number 246-002

Hyvinkää, 05850, Finland

Location

Investigational Site Number 246-004

Pori, 28210, Finland

Location

Investigational Site Number 246-003

Seinäjoki, 60220, Finland

Location

Investigational Site Number 250-006

Avignon, 84902, France

Location

Investigational Site Number 250-009

Béziers, 34525, France

Location

Investigational Site Number 250-002

Bron, 69677, France

Location

Investigational Site Number 250-007

Cholet, 49300, France

Location

Investigational Site Number 250-008

Lyon, 69275, France

Location

Investigational Site Number 250-010

Nîmes, 30029, France

Location

Investigational Site Number 250-003

Poitiers, 86021, France

Location

Investigational Site Number 250-004

Toulouse, 31076, France

Location

Investigational Site Number 250-005

Valence, 26953, France

Location

Investigational Site Number 250-001

Vandœuvre-lès-Nancy, 54511, France

Location

Investigational Site Number 276-003

Berlin, 13055, Germany

Location

Investigational Site Number 276-006

Bernau, 16321, Germany

Location

Investigational Site Number 276-001

Bonn, 53115, Germany

Location

Investigational Site Number 276-011

Dresden, 01099, Germany

Location

Investigational Site Number 276-010

Frankfurt am Main, 60594, Germany

Location

Investigational Site Number 276-002

Hamburg, 22041, Germany

Location

Investigational Site Number 276-008

Hamburg, 22527, Germany

Location

Investigational Site Number 276-009

Heidenau, 01809, Germany

Location

Investigational Site Number 276-004

Kiel, 24105, Germany

Location

Investigational Site Number 276-005

Ludwigsburg, 71634, Germany

Location

Investigational Site Number 276-007

Paderborn, 33098, Germany

Location

Investigational Site Number 376002

Ashkelon, Israel

Location

Investigational Site Number 376001

Beer Yaakov, Israel

Location

Investigational Site Number 380-005

Ancona, 60100, Italy

Location

Investigational Site Number 380-002

Barga, 55051, Italy

Location

Investigational Site Number 380-004

Catania, 95124, Italy

Location

Investigational Site Number 380-001

Como, 22100, Italy

Location

Investigational Site Number 380-006

Cortona, 52042, Italy

Location

Investigational Site Number 380-011

Mestre, 30174, Italy

Location

Investigational Site Number 380-010

Palermo, 90127, Italy

Location

Investigational Site Number 380-007

Roma, 00168, Italy

Location

Investigational Site Number 380-003

Roma, 00169, Italy

Location

Investigational Site Number 380-009

San Daniele del Friuli, 33038, Italy

Location

Investigational Site Number 380-012

Varese, 21100, Italy

Location

Investigational Site Number 484017

Aguascalientes, 20230, Mexico

Location

Investigational Site Number 484012

Chihuahua City, 31238, Mexico

Location

Investigational Site Number 484008

Guadalajara, 44200, Mexico

Location

Investigational Site Number 484009

Guadalajara, 44600, Mexico

Location

Investigational Site Number 484015

Guadalajara, 44600, Mexico

Location

Investigational Site Number 484002

León, 37150, Mexico

Location

Investigational Site Number 484016

México, 06140, Mexico

Location

Investigational Site Number 484004

México, 07760, Mexico

Location

Investigational Site Number 484005

Monterrey, 64460, Mexico

Location

Investigational Site Number 484003

Monterrey, 64710, Mexico

Location

Investigational Site Number 484001

Querétaro, 76000, Mexico

Location

Investigational Site Number 484013

Saltillo, 25230, Mexico

Location

Investigational Site Number 484011

Tijuana, 22450, Mexico

Location

Investigational Site Number 528003

Amsterdam, Netherlands

Location

Investigational Site Number 528005

Goes, Netherlands

Location

Investigational Site Number 528002

Groningen, Netherlands

Location

Investigational Site Number 528001

Maastricht, Netherlands

Location

Investigational Site Number 528004

Rotterdam, Netherlands

Location

Investigational Site Number 620005

Amadora, 2720-276, Portugal

Location

Investigational Site Number 620001

Lisbon, 1169-024, Portugal

Location

Investigational Site Number 410001

Seoul, 152-703, South Korea

Location

Investigational Site Number 410002

Seoul, South Korea

Location

Investigational Site Number 410003

Seoul, South Korea

Location

Investigational Site Number 410004

Seoul, South Korea

Location

Investigational Site Number 410005

Seoul, South Korea

Location

Investigational Site Number 410006

Suwon, 443-721, South Korea

Location

Investigational Site Number 724008

A Coruña, 15006, Spain

Location

Investigational Site Number 724004

El Palmar (murcia), 30120, Spain

Location

Investigational Site Number 724005

L'Hospitalet de Llobregat, 08907, Spain

Location

Investigational Site Number 724003

Lleida, Spain

Location

Investigational Site Number 724010

Madrid, 28034, Spain

Location

Investigational Site Number 724001

Madrid, 28040, Spain

Location

Investigational Site Number 724002

Majadahonda, 28222, Spain

Location

Investigational Site Number 724006

Seville, 41071, Spain

Location

Investigational Site Number 724007

Tarragona, 43007, Spain

Location

Investigational Site Number 724009

Valencia, 46014, Spain

Location

Investigational Site Number 756001

Basel, 4031, Switzerland

Location

Investigational Site Number 756002

Sankt Gallen, 9007, Switzerland

Location

Investigational Site Number 158006

Kaohsiung City, 807, Taiwan

Location

Investigational Site Number 158005

Kaohsiung Hsien,, Taiwan

Location

Investigational Site Number 158004

Taichung, 402, Taiwan

Location

Investigational Site Number 158003

Taichung, 407, Taiwan

Location

Investigational Site Number 158009

Taichung, Taiwan

Location

Investigational Site Number 158002

Taipei, 100, Taiwan

Location

Investigational Site Number 158001

Taipei, Taiwan

Location

Investigational Site Number 158008

Taipei, Taiwan

Location

Investigational Site Number 158007

Tao Yuan Hsien, Taiwan

Location

Investigational Site Number 826006

Belfast, BT126BA, United Kingdom

Location

Investigational Site Number 826-005

Bournemouth, BH77DW, United Kingdom

Location

Investigational Site Number 826-001

Carshalton, SM51AA, United Kingdom

Location

Investigational Site Number 826-002

Gloucester, GL13NN, United Kingdom

Location

Investigational Site Number 826-007

Wrexham, LL137TD, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 32500725 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Dronedarone

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amiodarone; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2010
• First Posted: June 9, 2010
• Study Start: September 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: January 23, 2012

Record last verified: 2012-01

Locations

FI (4); ME (13); GB (5); IT (11); PT (2); ES (1); NL (5); KR (6); CH (2); AU (13); FR (10); DE (11); TW (9); IL (2)