E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003658 |
E.1.2 | Term | Atrial fibrillation |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
Demonstrate the efficacy of dronedarone in preventing cardiovascular death |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
PALLAS Genomic and Biomarker Sub-study Date: 30 April 2010 - Version 1 |
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E.3 | Principal 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
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E.4 | Principal 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) |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Composite endpoint of first stroke, systemic arterial embolism, myocardial infarction or cardiovascular death • Composite endpoint of first unplanned cardiovascular hospitalization or death from any cause |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 251 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |