A Trial With Dronedarone to Prevent Hospitalization or Death in Patients With Atrial Fibrillation
Condition: Atrial Fibrillation; Atrial Flutter
MeSH terms: Atrial Fibrillation; Atrial Flutter
Intervention: dronedarone (SR33589); placebo
Intervention description: oral administration (tablets); oral administration (tablets)
Intervention MeSH terms: Dronedarone
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 4628.0
Sex: All
Minimum age: 70 Years
Healthy volunteers: No
Keywords: Mortality, Hospitalization

Summary:

      To assess the efficacy of dronedarone in preventing cardiovascular hospitalization or death
      from any cause in a population of high-risk patients with atrial fibrillation/atrial flutter
      (AF/AFL).

      To assess that dronedarone is well tolerated in this population.
    

Eligibility criteria:

        Inclusion Criteria:

          -  1. Patients aged 75 years or older (70 years before protocol amendment 1), or patients
             aged at least 70 years (any age before protocol amendment 1) with one or more of the
             following risk factors at baseline:

               -  Hypertension (taking antihypertensive drugs of at least two different classes)

               -  Diabetes

               -  Prior cerebrovascular accident (stroke or transient ischemic attack) or systemic
                  embolism

               -  Left atrium diameter greater than or equal to 50 mm by echocardiography

               -  Left ventricular ejection fraction less than 0.40 by 2D-echocardiography
                  (two-dimensional echocardiography)

          -  2. Availability of one electrocardiogram (ECG) within the last 6 months, showing that
             the patient was or is in AF/AFL

          -  3. Availability of one ECG within the last 6 months, showing that the patient was or
             is in sinus rhythm

        Exclusion Criteria:

        General criteria:

          -  1. Refusal or inability to give informed consent to participate in the study

          -  2. Any non cardiovascular illness or disorder that could preclude participation or
             severely limit survival including cancer with metastasis and organ transplantation
             requiring immune suppression

          -  3. Pregnant women (pregnancy test must be negative) or women of childbearing potential
             not on adequate birth control: only women with a highly effective method of
             contraception [oral contraception or intra-uterine device (IUD)] or sterile can be
             randomized.

          -  4. Breastfeeding women

          -  5. Previous (2 preceding months) or current participation in another clinical trial
             with an investigational drug (under development) or with an investigational device

          -  6. Previous participation in this trial

        Criteria Related to a cardiac condition:

          -  7. Patients in permanent atrial fibrillation

          -  8. Patients in unstable hemodynamic condition such as acute pulmonary edema within 12
             hours prior to start of study medication; cardiogenic shock; treatment with
             intra-venous pressor agents; patients on respirator; congestive heart failure of stage
             NYHA IV (New York Heart Association classification) within the last 4 weeks;
             uncorrected, hemodynamically significant primary obstructive valvular disease;
             hemodynamically significant obstructive cardiomyopathy; a cardiac operation or
             revascularization procedure within 4 weeks preceding randomization

          -  9. Planned major non-cardiac or cardiac surgery or procedures including surgery for
             valvular heart disease, coronary artery bypass graft (CABG) , percutaneous coronary
             intervention (PCI) , or on urgent cardiac transplantation list

          -  10. Acute myocarditis or constrictive pericarditis

          -  11. Bradycardia < 50 bpm and/or PR-interval > 0.28 sec on the last 12-lead ECG

          -  12. Significant sinus node disease (documented pause of 3 seconds or more) or 2nd or
             3rd degree atrioventricular block (AV-block) unless treated with a pacemaker

        Criteria Related to Concomitant Medications:

          -  13. Need of a concomitant medication that is prohibited in this trial, including the
             requirement for Vaughan Williams Class I and III anti-arrhythmic drugs, that would
             preclude the use of study drug during the planned study period

        Criteria Related to Laboratory Abnormalities:

          -  14. Plasma potassium < 3.5 mmol/l (as anti-arrhythmic drugs can be arrhythmogenic in
             patients with hypokalemia, this must be corrected prior to randomization)

          -  15. A calculated Glomerular Filtration Rate (GFR) at baseline <10 ml/min using the
             Cockroft Gault formula