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 - Permanent Atrial fibriLLAtion outcome Study using Dronedarone on top of standard therapy (PALLAS)

• Conditions: Atrial Fibrillation; MedDRA version: 12.1Level: LLTClassification code 10003658Term: Atrial fibrillation

• Registration Number: EUCTR2010-019791-73-GR
• Lead Sponsor: Sanofi-aventis recherche & développement

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-10-04
• Last Update Posted: 3 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 10800

Inclusion Criteria

I 01. Patients in permanent atrial fibrillation 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 atrial fibrillation or atrial flutter
• Availability of documentation (including either rhythm strips or medical report of the
rhythm) showing that the patient was in atrial fibrillation or atrial flutter at least 6
months prior to randomization
• No evidence of sinus rhythm in the period between these two documentations of atrial
fibrillation*
• Patient and physician decision to allow atrial fibrillation to continue without further
efforts to restore sinus rhythm
I 02. Patients aged 65 years or older with at least one of the following risk criteria:
• Coronary artery disease**
• Prior stroke or TIA (confirmed by a neurologist)
• Symptomatic heart failure***
• Left ventricular ejection fraction less than or equal to 0.40
• Peripheral arterial occlusive disease****
• Aged 75 years or older with both hypertension and diabetes mellitus*****
I 03. Signed written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

E 01. Patients in paroxysmal atrial fibrillation
E 02. Patients in persistent atrial fibrillation without a decision to allow atrial fibrillation to
continue without further efforts to restore sinus rhythm
E 03. Patients with atrioventricular node ablation or previously diagnosed with permanent thirddegree
AV block
E 04. Patients with an implanted cardiac defibrillator
E 05. Any noncardiovascular illness or disorder that could preclude participation or severely
limit survival, including cancer with metastasis and organ transplantation requiring
immune suppression
E 06. Previous (2 preceding months) or current participation in another clinical trial with an
investigational drug (under development) or with an investigational device
E 07. Previous participation in this trial
E 08. Dronedarone treatment within 3 months prior to randomization
E 09. Patient is the Investigator or any Sub-Investigator, research assistant, pharmacist, trial
coordinator, other staff or relative thereof directly involved in the conduct of the protocol
E 10. Patient likely noncompliant to the trial procedures

Exclusion criteria related to the current knowledge of dronedarone
E 11. Patients with heart failure of NYHA class IV or recent unstable* NYHA class III
Unstable*: intensification of heart failure therapy (eg, increased diuretics, ACE / ARBs, or
inotropes) due to increased symptoms within one month prior to randomization.
E 12. Sustained daytime bradycardia <50 bpm without a functioning electronic pacemaker
E 13. QTc interval >500 msec
E 14. Hypersensitivity to the active substance or to any of the excipients
E 15. Need for coadministration of strong CYP3A4 inhibitors, such as ketoconazole,
itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone and ritonavir leading
to systemic exposure
E 16. Need for coadministration of medicinal products inducing torsades de pointes such as
phenothiazines, cisapride, bepridil, tricyclic antidepressants, terfenadine and certain oral
macrolides, or class I and III antiarrhythmics)
E 17. Severe hepatic impairment
E 18. Any additional contraindication according to local labeling of dronedarone (when available)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main 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;Primary end point(s): • Composite endpoint of first stroke, systemic arterial embolism, myocardial infarction or cardiovascular death<br>• Composite endpoint of first unplanned cardiovascular hospitalization or death from any cause