Permanent Atrial fibriLLAtion Outcome Study Using Dronedarone on Top of Standard Therapy

Atrial Fibrillation Clinical Trial

— PALLAS  

Official title:

A Randomized, Double Blind, Placebo Controlled, Parallel Group Trial for Assessing the Clinical Benefit of Dronedarone 400mg BID on Top of Standard Therapy in Patients With Permanent Atrial Fibrillation and Additional Risk Factors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01151137
• Other study ID #: EFC11405
• Secondary ID: 2010-019791-73U1
• Status: Terminated
• Phase: Phase 3
• First received: June 22, 2010
• Last updated: October 23, 2012
• Start date: July 2010
• Est. completion date: September 2011

Study information

• Verified date: October 2012
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

• Demonstrate the efficacy of Dronedarone in preventing major cardiovascular events (stroke, systemic arterial embolism, myocardial infarction or cardiovascular death) or unplanned cardiovascular hospitalization or death from any cause in patients with permanent Atrial Fibrillation [AF] and additional risk factors

Secondary Objective:

• Demonstrate the efficacy of Dronedarone in preventing cardiovascular death

This was an event-driven study where a common study end date [CSED] was to be determined by Steering Committee based on the number of events (stroke, systemic arterial embolism, myocardial infarction or cardiovascular death).

Description:

The study period per participant was variable depending on the enrollment in the study.

A final follow-up visit had to occur within 1 month after the CSED.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3236
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

Inclusion criteria:

• Permanent AF defined by the presence of all of the following criteria:

• Availability of one 12-lead ECG not more than 14 days prior to randomization showing that the patient is in AF or atrial flutter;

• Availability of documentation (including either rhythm strips or medical report of the rhythm) showing that the patient was in AF or atrial flutter at least 6 months prior to randomization;

• No evidence of sinus rhythm in the period between these two documentations of AF;

• Decision of the patient and physician to allow AF to continue without further efforts to restore sinus rhythm.

• At least one of the following risk criteria:

• Coronary artery disease;

• Prior stroke or Transient Ischemic Attack [TIA];

• Symptomatic heart failure;

• Left ventricular ejection fraction [LVEF] less or equal to 0.40;

• Peripheral arterial occlusive disease;

• Aged 75 years or older with both hypertension and diabetes mellitus.

Exclusion criteria:

• Paroxysmal AF;

• Persistent AF without a decision to allow AF to continue without further efforts to restore sinus rhythm;

• Heart failure of New-York Heart Association [NYHA] class IV or recent unstable NYHA class III.

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: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• Dronedarone
Film-coated tablet Oral administration under fed conditions (during breakfast and dinner)
• Placebo (for Dronedarone)
film-coated tablet strictly identical in appearance Oral administration under fed conditions (during breakfast and dinner)

Locations

Country	Name	City	State
Argentina	Sanofi-Aventis Administrative Office	Buenos Aires
Australia	Sanofi-Aventis Administrative Office	Macquarie Park
Austria	Sanofi-Aventis Administrative Office	Vienna
Belgium	Sanofi-Aventis Administrative Office	Diegem
Brazil	Sanofi-Aventis Administrative Office	Sao Paulo
Bulgaria	Sanofi-Aventis Administrative Office	Sofia
Canada	Sanofi-Aventis Administrative Office	Laval
Chile	Sanofi-Aventis Administrative Office	Providencia Santiago
Czech Republic	Sanofi-Aventis Administrative Office	Praha
Denmark	Sanofi-Aventis Administrative Office	Horsholm
Finland	Sanofi-Aventis Administrative Office	Helsinki
France	Sanofi-Aventis Administrative Office	Paris
Germany	Sanofi-Aventis Administrative Office	Frankfurt
Greece	Sanofi-Aventis Administrative Office	Kallithea
Hong Kong	Sanofi-Aventis Administrative Office	Hong Kong
Hungary	Sanofi-Aventis Administrative Office	Budapest
Israel	Sanofi-Aventis Administrative Office	Natanya
Italy	Sanofi-Aventis Administrative Office	Milan
Korea, Republic of	Sanofi-Aventis Administrative Office	Seoul
Malaysia	Sanofi-Aventis Administrative Office	Kuala Lumpur
Mexico	Sanofi-Aventis Administrative Office	Col. Coyoacan
Netherlands	Sanofi-Aventis Administrative Office	Gouda
New Zealand	Sanofi-Aventis Administrative Office	Auckland
Norway	Sanofi-Aventis Administrative Office	Lysaker
Poland	Sanofi-Aventis Administrative Office	Warsaw
Romania	Sanofi-Aventis Administrative Office	Bucuresti
Russian Federation	Sanofi-Aventis Administrative Office	Moscow
Singapore	Sanofi-Aventis Administrative Office	Singapore
Slovakia	Sanofi-Aventis Administrative Office	Bratislava
South Africa	Sanofi-Aventis Administrative Office	Gauteng
Spain	Sanofi-Aventis Administrative Office	Barcelona
Sweden	Sanofi-Aventis Administrative Office	Bromma
Switzerland	Sanofi-Aventis Administrative Office	Geneva
Taiwan	Sanofi-Aventis Administrative Office	Taipei
Ukraine	Sanofi-Aventis Administrative Office	Kiev
United Kingdom	Sanofi-Aventis Administrative Office	Guildford Surrey
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Israel,  Italy,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  New Zealand,  Norway,  Poland,  Romania,  Russian Federation,  Singapore,  Slovakia,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  Ukraine,  United Kingdom, 

References & Publications (1)

Connolly SJ, Camm AJ, Halperin JL, Joyner C, Alings M, Amerena J, Atar D, Avezum Á, Blomström P, Borggrefe M, Budaj A, Chen SA, Ching CK, Commerford P, Dans A, Davy JM, Delacrétaz E, Di Pasquale G, Diaz R, Dorian P, Flaker G, Golitsyn S, Gonzalez-Hermosil — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overview of Cardiovascular Events		From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)	No
Other	Overview of Adverse Events [AE]	AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.	from first study drug intake up to 10 days after the last study drug intake	Yes
Primary	Overview of the Two Co-primary Outcomes	First co-primary outcome was defined as the first event among stroke, systemic arterial embolism, Myocardial Infarctions [MI], or cardiovascular death.; Second co-primary outcome was defined as the first event among unscheduled cardiovascular hospitalization or death from any cause.; Both co-primary outcomes were determined based on the central review and adjudication by a blinded Adjudication Committee of all reported deaths (from any cause), MI, systemic arterial embolisms, strokes, Transient Ischemic Attacks [TIA], Heart Failure hospitalization and unplanned hospitalisations for cardiovascular cause.	From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)	No
Primary	Time to First Co-primary Outcome (Cumulative Incidence Function)	Time to first co-primary outcome was defined as the time from randomization to the first event among stroke, systemic arterial embolism, MI or cardiovascular death.; Cumulative incidence function in each treatment group was calculated using non-parametric Kaplan-Meier estimate.; 95% confidence interval was computed at each time-point using Greenwood's variance estimation.	From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)	No
Primary	Time to Second Co-primary Outcome (Cumulative Incidence Function)	Time to second co-primary outcome was defined as the time from randomization to the first event among unscheduled cardiovascular hospitalization or death from any cause.; Cumulative incidence function in each treatment group was calculated using non-parametric Kaplan-Meier estimate.; 95% confidence interval was computed at each time-point using Greenwood's variance estimation.	From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)	No
Secondary	Deaths	Deaths were classified according to the primary cause of death.	From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)	No
Secondary	Time to Cardiovascular Death (Cumulative Incidence Function)	Time to cardiovascular death was defined as the time from randomization to the death.; Cumulative incidence function in each treatment group was calculated using non-parametric Kaplan-Meier estimate.; 95% confidence interval was computed at each time-point using Greenwood's variance estimation.	From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)	No