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

• ClinicalTrials.gov Identifier: NCT01151137
• Recruitment Status: Terminated
• First Posted: June 25, 2010
• Results First Posted: October 26, 2012
• Last Update Posted: October 26, 2012
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Atrial Fibrillation	Drug: Dronedarone; Drug: Placebo (for Dronedarone)	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3236 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: July 2010
• Actual Primary Completion Date: September 2011
• Actual Study Completion Date: September 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dronedarone; Dronedarone 400 mg twice a day until the CSED	Drug: Dronedarone; Film-coated tablet Oral administration under fed conditions (during breakfast and dinner); Other Names: MULTAQ; SR33589
Placebo Comparator: placebo; Placebo (for Dronedarone) twice a day until the CSED	Drug: Placebo (for Dronedarone); film-coated tablet strictly identical in appearance Oral administration under fed conditions (during breakfast and dinner)

Outcome Measures

Primary Outcome Measures :

1. Overview of the Two Co-primary Outcomes [ Time Frame: From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year) ]

   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.

2. Time to First Co-primary Outcome (Cumulative Incidence Function) [ Time Frame: From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year) ]

   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.

3. Time to Second Co-primary Outcome (Cumulative Incidence Function) [ Time Frame: From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year) ]

   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.

Secondary Outcome Measures :

1. Deaths [ Time Frame: From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year) ]
   Deaths were classified according to the primary cause of death.
2. Time to Cardiovascular Death (Cumulative Incidence Function) [ Time Frame: From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year) ]

   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.

Other Outcome Measures:

1. Overview of Cardiovascular Events [ Time Frame: From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year) ]
2. Overview of Adverse Events [AE] [ Time Frame: from first study drug intake up to 10 days after the last study drug intake ]
   AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.

Eligibility Criteria

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, New Jersey

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, United States, 08807

Argentina

Sanofi-Aventis Administrative Office

Buenos Aires, Argentina

Australia

Sanofi-Aventis Administrative Office

Macquarie Park, Australia

Austria

Sanofi-Aventis Administrative Office

Vienna, Austria

Belgium

Sanofi-Aventis Administrative Office

Diegem, Belgium

Brazil

Sanofi-Aventis Administrative Office

Sao Paulo, Brazil

Bulgaria

Sanofi-Aventis Administrative Office

Sofia, Bulgaria

Canada

Sanofi-Aventis Administrative Office

Laval, Canada

Chile

Sanofi-Aventis Administrative Office

Providencia Santiago, Chile

Czech Republic

Sanofi-Aventis Administrative Office

Praha, Czech Republic

Denmark

Sanofi-Aventis Administrative Office

Horsholm, Denmark

Finland

Sanofi-Aventis Administrative Office

Helsinki, Finland

France

Sanofi-Aventis Administrative Office

Paris, France

Germany

Sanofi-Aventis Administrative Office

Frankfurt, Germany

Greece

Sanofi-Aventis Administrative Office

Kallithea, Greece

Hong Kong

Sanofi-Aventis Administrative Office

Hong Kong, Hong Kong

Hungary

Sanofi-Aventis Administrative Office

Budapest, Hungary

Israel

Sanofi-Aventis Administrative Office

Natanya, Israel

Italy

Sanofi-Aventis Administrative Office

Milan, Italy

Korea, Republic of

Sanofi-Aventis Administrative Office

Seoul, Korea, Republic of

Malaysia

Sanofi-Aventis Administrative Office

Kuala Lumpur, Malaysia

Mexico

Sanofi-Aventis Administrative Office

Col. Coyoacan, Mexico

Netherlands

Sanofi-Aventis Administrative Office

Gouda, Netherlands

New Zealand

Sanofi-Aventis Administrative Office

Auckland, New Zealand

Norway

Sanofi-Aventis Administrative Office

Lysaker, Norway

Poland

Sanofi-Aventis Administrative Office

Warsaw, Poland

Romania

Sanofi-Aventis Administrative Office

Bucuresti, Romania

Russian Federation

Sanofi-Aventis Administrative Office

Moscow, Russian Federation

Singapore

Sanofi-Aventis Administrative Office

Singapore, Singapore

Slovakia

Sanofi-Aventis Administrative Office

Bratislava, Slovakia

South Africa

Sanofi-Aventis Administrative Office

Gauteng, South Africa

Spain

Sanofi-Aventis Administrative Office

Barcelona, Spain

Sweden

Sanofi-Aventis Administrative Office

Bromma, Sweden

Switzerland

Sanofi-Aventis Administrative Office

Geneva, Switzerland

Taiwan

Sanofi-Aventis Administrative Office

Taipei, Taiwan

Ukraine

Sanofi-Aventis Administrative Office

Kiev, Ukraine

United Kingdom

Sanofi-Aventis Administrative Office

Guildford Surrey, United Kingdom

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

Publications of Results:

Connolly SJ, Camm AJ, Halperin JL, Joyner C, Alings M, Amerena J, Atar D, Avezum A, Blomstrom P, Borggrefe M, Budaj A, Chen SA, Ching CK, Commerford P, Dans A, Davy JM, Delacretaz E, Di Pasquale G, Diaz R, Dorian P, Flaker G, Golitsyn S, Gonzalez-Hermosillo A, Granger CB, Heidbuchel H, Kautzner J, Kim JS, Lanas F, Lewis BS, Merino JL, Morillo C, Murin J, Narasimhan C, Paolasso E, Parkhomenko A, Peters NS, Sim KH, Stiles MK, Tanomsup S, Toivonen L, Tomcsanyi J, Torp-Pedersen C, Tse HF, Vardas P, Vinereanu D, Xavier D, Zhu J, Zhu JR, Baret-Cormel L, Weinling E, Staiger C, Yusuf S, Chrolavicius S, Afzal R, Hohnloser SH; PALLAS Investigators. Dronedarone in high-risk permanent atrial fibrillation. N Engl J Med. 2011 Dec 15;365(24):2268-76. doi: 10.1056/NEJMoa1109867. Epub 2011 Nov 14. Erratum In: N Engl J Med. 2012 Feb 16;366(7):672.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hohnloser SH, Halperin JL, Camm AJ, Gao P, Radzik D, Connolly SJ; PALLAS investigators. Interaction between digoxin and dronedarone in the PALLAS trial. Circ Arrhythm Electrophysiol. 2014 Dec;7(6):1019-25. doi: 10.1161/CIRCEP.114.002046. Epub 2014 Nov 6.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT01151137
• Other Study ID Numbers: EFC11405; 2010-019791-73 ( EudraCT Number ); U1111-1116-5566 ( Other Identifier: UTN )
• First Posted: June 25, 2010
• Results First Posted: October 26, 2012
• Last Update Posted: October 26, 2012
• Last Verified: October 2012

Additional relevant MeSH terms:

Atrial Fibrillation; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Dronedarone; Anti-Arrhythmia Agents