search
Back to results

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

Primary Purpose

Atrial Fibrillation

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Dronedarone
Placebo (for Dronedarone)
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atrial Fibrillation

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Dronedarone

placebo

Arm Description

Dronedarone 400 mg twice a day until the CSED

Placebo (for Dronedarone) twice a day until the CSED

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

Deaths
Deaths were classified according to the primary cause of death.
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.

Full Information

First Posted
June 22, 2010
Last Updated
October 23, 2012
Sponsor
Sanofi
search

1. Study Identification

Unique Protocol Identification Number
NCT01151137
Brief Title
Permanent Atrial fibriLLAtion Outcome Study Using Dronedarone on Top of Standard Therapy
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2012
Overall Recruitment Status
Terminated
Why Stopped
The study was stopped because of safety concerns
Study Start Date
July 2010 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

Data Monitoring Committee
Yes

5. 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
3236 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dronedarone
Arm Type
Experimental
Arm Description
Dronedarone 400 mg twice a day until the CSED
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Placebo (for Dronedarone) twice a day until the CSED
Intervention Type
Drug
Intervention Name(s)
Dronedarone
Other Intervention Name(s)
MULTAQ, SR33589
Intervention Description
Film-coated tablet Oral administration under fed conditions (during breakfast and dinner)
Intervention Type
Drug
Intervention Name(s)
Placebo (for Dronedarone)
Intervention Description
film-coated tablet strictly identical in appearance Oral administration under fed conditions (during breakfast and dinner)
Primary Outcome Measure Information:
Title
Overview of the Two Co-primary Outcomes
Description
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.
Time Frame
From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)
Title
Time to First Co-primary Outcome (Cumulative Incidence Function)
Description
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.
Time Frame
From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)
Title
Time to Second Co-primary Outcome (Cumulative Incidence Function)
Description
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.
Time Frame
From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)
Secondary Outcome Measure Information:
Title
Deaths
Description
Deaths were classified according to the primary cause of death.
Time Frame
From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)
Title
Time to Cardiovascular Death (Cumulative Incidence Function)
Description
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.
Time Frame
From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)
Other Pre-specified Outcome Measures:
Title
Overview of Cardiovascular Events
Time Frame
From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)
Title
Overview of Adverse Events [AE]
Description
AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.
Time Frame
from first study drug intake up to 10 days after the last study drug intake

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Sanofi-Aventis Administrative Office
City
Bridgewater
State/Province
New Jersey
ZIP/Postal Code
08807
Country
United States
Facility Name
Sanofi-Aventis Administrative Office
City
Buenos Aires
Country
Argentina
Facility Name
Sanofi-Aventis Administrative Office
City
Macquarie Park
Country
Australia
Facility Name
Sanofi-Aventis Administrative Office
City
Vienna
Country
Austria
Facility Name
Sanofi-Aventis Administrative Office
City
Diegem
Country
Belgium
Facility Name
Sanofi-Aventis Administrative Office
City
Sao Paulo
Country
Brazil
Facility Name
Sanofi-Aventis Administrative Office
City
Sofia
Country
Bulgaria
Facility Name
Sanofi-Aventis Administrative Office
City
Laval
Country
Canada
Facility Name
Sanofi-Aventis Administrative Office
City
Providencia Santiago
Country
Chile
Facility Name
Sanofi-Aventis Administrative Office
City
Praha
Country
Czech Republic
Facility Name
Sanofi-Aventis Administrative Office
City
Horsholm
Country
Denmark
Facility Name
Sanofi-Aventis Administrative Office
City
Helsinki
Country
Finland
Facility Name
Sanofi-Aventis Administrative Office
City
Paris
Country
France
Facility Name
Sanofi-Aventis Administrative Office
City
Frankfurt
Country
Germany
Facility Name
Sanofi-Aventis Administrative Office
City
Kallithea
Country
Greece
Facility Name
Sanofi-Aventis Administrative Office
City
Hong Kong
Country
Hong Kong
Facility Name
Sanofi-Aventis Administrative Office
City
Budapest
Country
Hungary
Facility Name
Sanofi-Aventis Administrative Office
City
Natanya
Country
Israel
Facility Name
Sanofi-Aventis Administrative Office
City
Milan
Country
Italy
Facility Name
Sanofi-Aventis Administrative Office
City
Seoul
Country
Korea, Republic of
Facility Name
Sanofi-Aventis Administrative Office
City
Kuala Lumpur
Country
Malaysia
Facility Name
Sanofi-Aventis Administrative Office
City
Col. Coyoacan
Country
Mexico
Facility Name
Sanofi-Aventis Administrative Office
City
Gouda
Country
Netherlands
Facility Name
Sanofi-Aventis Administrative Office
City
Auckland
Country
New Zealand
Facility Name
Sanofi-Aventis Administrative Office
City
Lysaker
Country
Norway
Facility Name
Sanofi-Aventis Administrative Office
City
Warsaw
Country
Poland
Facility Name
Sanofi-Aventis Administrative Office
City
Bucuresti
Country
Romania
Facility Name
Sanofi-Aventis Administrative Office
City
Moscow
Country
Russian Federation
Facility Name
Sanofi-Aventis Administrative Office
City
Singapore
Country
Singapore
Facility Name
Sanofi-Aventis Administrative Office
City
Bratislava
Country
Slovakia
Facility Name
Sanofi-Aventis Administrative Office
City
Gauteng
Country
South Africa
Facility Name
Sanofi-Aventis Administrative Office
City
Barcelona
Country
Spain
Facility Name
Sanofi-Aventis Administrative Office
City
Bromma
Country
Sweden
Facility Name
Sanofi-Aventis Administrative Office
City
Geneva
Country
Switzerland
Facility Name
Sanofi-Aventis Administrative Office
City
Taipei
Country
Taiwan
Facility Name
Sanofi-Aventis Administrative Office
City
Kiev
Country
Ukraine
Facility Name
Sanofi-Aventis Administrative Office
City
Guildford Surrey
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
22082198
Citation
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.
Results Reference
result
PubMed Identifier
25378467
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs