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

This study has been terminated.
(The study was stopped because of safety concerns)
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01151137
First received: June 22, 2010
Last updated: October 23, 2012
Last verified: October 2012
Results First Received: September 14, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Atrial Fibrillation
Interventions: Drug: Dronedarone
Drug: Placebo (for Dronedarone)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

Recruitment initiated in July 2010 was discontinued on July 6, 2011 upon recommendations of the Data Monitoring Committee due to an increased number of observed cardiovascular events in the Dronedarone group. The common study end date [CSED] was defined as July 15, 2011.

At that time 494 sites in 37 countries had enrolled at least one patient.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Assignment to groups was done centrally using an Interactive Voice Response System [IVRS] or an Interactive Web Response System [IWRS] in a 1:1 ratio.

A total of 3236 participants were randomized at 489 sites (instead of 10800 as initially planned). The median duration of their participation in the study was 3.5 months.


Reporting Groups
  Description
Placebo Placebo twice daily until the CSED (median treatment duration of 87.5 days)
Dronedarone Dronedarone 400 mg twice daily until the CSED (median treatment duration of 74 days)

Participant Flow:   Overall Study
    Placebo   Dronedarone
STARTED   1617   1619 
Treated   1610 [1]   1613 
Discontinued Treatment   171   342 
COMPLETED   1601   1591 
NOT COMPLETED   16   28 
Death                15                27 
Lost to Follow-up                1                1 
[1] One participant randomized to the placebo group received Dronedarone for 7 days by mistake



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo Placebo twice daily until the CSED (median treatment duration of 87.5 days)
Dronedarone Dronedarone 400 mg twice daily until the CSED (median treatment duration of 74 days)
Total Total of all reporting groups

Baseline Measures
   Placebo   Dronedarone   Total 
Overall Participants Analyzed 
[Units: Participants]
 1617   1619   3236 
Age 
[Units: Years]
Mean (Standard Deviation)
 75.0  (5.9)   75.0  (5.9)   75.0  (5.9) 
Gender 
[Units: Participants]
     
Female   577   568   1145 
Male   1040   1051   2091 
Region of Enrollment [1] 
[Units: Participants]
     
North America   281   266   547 
South America   227   236   463 
Western Europe   459   475   934 
Eastern Europe   495   488   983 
Asia   53   47   100 
Rest of the word   102   107   209 
[1]

Regions were defined as follows:

  • North America: Canada, United States
  • South America: Argentina, Brazil, Chile, Mexico
  • Western Europe: Austria, Belgium, Denmark, Finland, France, Germany, Greece, Italy, Netherlands, Norway, Spain, Sweden, Switzerland, United Kingdom
  • Eastern Europe: Bulgaria, Czech Republic, Hungary, Poland, Romania, Russian Federation, Slovakia, Ukraine Asia: Hong Kong, Republic of Korea, Malaysia, Singapore, Taiwan Rest of the World: Australia, Israel, New zealand, South Africa
Permanent atrial fibrillation [AF] history 
[Units: Participants]
     
6 months to 2 years   490   498   988 
> 2 years   1124   1119   2243 
Unknown   3   2   5 
CHADS2 Score [1] 
[Units: Participants]
     
< 2   172   191   363 
≥ 2   1444   1427   2871 
Unavailable   1   1   2 
[1]

CHADS2 is a risk-prediction score ranging from 0 to 6 used estimate Stroke Risk in Atrial Fibrillation patients.

CHADS2 score is obtained by adding together the points that correspond to the conditions that are present:

  • C: Congestive Heart Failure history: 1 point
  • H: Hypertension history: 1 point
  • A: Age ≥75 years: 1 point
  • D: Diabetes Mellitus history: 1 point
  • S: Stroke symptoms previously or Transient Ischemic Attack [TIA]: 2 points
New York Heart Association [NYHA] class [1] 
[Units: Participants]
     
No congestive heart failure [CHF]   535   512   1047 
NYHA Class I   209   234   443 
NYHA Class II   749   732   1481 
NYHA Class III   124   141   265 
[1]

NYHA classification is a functional classification that places the patient in one of 4 categories, based on how much he/she is limited during physical activity:

  • Class I: no limitation of activities; the patient suffers no symptoms from ordinary activities.
  • Class II: slight, mild limitation of activity; the patient is comfortable with rest or with mild exertion.
  • Class III: marked limitation of activity; the patient is comfortable only at rest.
  • Class IV: complete rest, confined to bed or chair; any physical activity brings on discomfort and symptoms occur at rest.


  Outcome Measures
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1.  Primary:   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) ]

2.  Primary:   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) ]

3.  Primary:   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) ]

4.  Secondary:   Deaths   [ Time Frame: From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year) ]

5.  Secondary:   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) ]

6.  Other Pre-specified:   Overview of Cardiovascular Events   [ Time Frame: From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year) ]

7.  Other Pre-specified:   Overview of Adverse Events [AE]   [ Time Frame: from first study drug intake up to 10 days after the last study drug intake ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Given that the study was prematurely discontinued after 3236 patients were randomized (30% of the initial planned number), p-values were provided for information without any adjustment for multiplicity.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Trial Transparency Team
Organization: sanofi-aventis
e-mail: Contact_US@sanofi.com


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

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01151137     History of Changes
Other Study ID Numbers: EFC11405
2010-019791-73 ( EudraCT Number )
U1111-1116-5566 ( Other Identifier: UTN )
Study First Received: June 22, 2010
Results First Received: September 14, 2012
Last Updated: October 23, 2012
Health Authority: United States: Food and Drug Administration