Primary Investigator: Mary Dohrmann, MD
Study Coordinator: Kathy Belew, CNS-BC
Status: Active - open to enrollment
Study Title: A randomized, double blind, placebo controlled, parallel group trial for assessing the clinical benefit of Dronedarone 400 mg BID on top of standard therapy in patients with permanent atrial fibrillation and additional risk factors (PALLAS)
Purpose: The primary objective of this trial is to 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 and additional risk factors.
1. 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 six 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.
2. 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.*****
* If a patient has been cardioverted and sinus rhythm was sustained for less than 60 minutes after the intervention this will not be regarded as evidence of sinus rhythm
Exclusion Criteria: Patients meeting all the above inclusion criteria will be screened for the following exclusion criteria which are sorted and numbered in the following two subsections:
Exclusion criteria related to study methodology:
- Patients in paroxysmal atrial fibrillation.
- Patients in persistent atrial fibrillation without a decision to allow atrial fibrillation to continue without further efforts to restore sinus rhythm.
- Patients with atrioventricular node ablation or previously diagnosed with permanent third degree AV block.
- Patients with an implanted cardiac defibrillator.
- Any noncardiovascular illness or disorder that could preclude participation or severely limit survival, including cancer with metastasis and organ transplantation requiring immune suppression.
- Previous (two preceding months) or current participation in another clinical trial with an investigational drug (under development) or with an investigational device.
- Previous participation in this trial.
- Dronedarone treatment within three months prior to randomization.
- 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.
- Patient likely noncompliant to the trial procedures.
Exclusion criteria related to the current knowledge of dronedarone:
11. Patients with heart failure of NYHA class IV or recent unstable* NYHA class III.
Unstable*: intensification of heart failure therapy (e.g., increased diuretics, ACE/ARBs, or inotropes) due to increased symptoms within one month prior to randomization.
12. Sustained daytime bradycardia <50 bpm without a functioning electronic pacemaker.
13. QTc interval >500 msec.
14. Hypersensitivity to the active substance or to any of the excipients.
15. Need for coadministration of strong CYP3A4 inhibitors, such as ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone and ritonavir leading to systemic exposure.
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).
17. Severe hepatic impairment.
18. Any additional contraindication according to local labeling of dronedarone (when available).
1. Determine if patient fits major study criteria.
2. Determine if patient is interested in joining a clinical trial.
3. Call Kathy Belew (beeper 573-499-8063) and/or on-call research nurse (on-call beeper 573-499-8084) or Dr. Dohrmann to complete screening of subject.