Primary:To assess whether the addition of dronedarone (Multaq®) to existing conventional rate control therapy leads to a reduced ventricular rate after 1 week in patients with a high HR at rest during AF in comparison to an increase of conventional…
ID
Source
Brief title
Condition
- Cardiac arrhythmias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Ventricular rate after 1 week.
Secondary outcome
- Ventricular rate after 3 months.
- Number of registered AF episodes.
- Number of symptomatic AF episodes.
- Severity of AF and AF-like symptoms.
- Adverse events.
- Rate of premature study discontinuation (*going off study prematurely*).
- Number of symptomatic episodes of bradycardia.
- Incidence of low heart rate (<60 bpm).
Background summary
Previous studies have shown no evident difference in benefit between rate or
rhythm control strategies in the management of AF. In current treatment
guidelines it is recommended to start with rate control therapy and switch to
rhythm control in case of rate control fails or cannot be intensified. Adverse
events and treatment discontinuation are common with conventional rhythm
control therapy.
If AF patients are inadequately controlled (i.e. HR at rest > 80 bpm) on rate
control treatment, adjustment, i.e.a dose increase or a switch to rhythm
control is indicated. The physician*s preference may be influenced by treatment
duration, number of rate control agents and/or severity of symptoms.
The combination of rhythm and rate control properties with good tolerability
and a lack of proarrhythmic effects suggests that dronedarone may address
several of the shortcomings of current treatment options. The effects of adding
dronedarone to conventional rate control in comparison to a dose increase of
conventional therapy in insufficiently controlled AF patients are not yet
documented. These data will help to position this promising new drug in the
existing treatment options for AF.
Therefore the current study will address the effects on ventricular rate during
AF of the addition of dronedarone to the existing rate control treatment with a
beta blocker and/or a calcium antagonist in comparison to dose increase of the
existing treatment in patients with insufficiently controlled persistent AF.
Study objective
Primary:
To assess whether the addition of dronedarone (Multaq®) to existing
conventional rate control therapy leads to a reduced ventricular rate after 1
week in patients with a high HR at rest during AF in comparison to an increase
of conventional therapy.
Secondary:
To compare both study arms with regard to:
- Ventricular rate after 3 months.
- Number of registered AF episodes.
- Number of symptomatic AF episodes.
- Severity of AF and AF-like symptoms.
- Adverse events.
- Rate of premature study discontinuation (*going off study prematurely*).
- Number of symptomatic episodes of bradycardia.
- Incidence of low heart rate (<60 bpm).
Study design
Randomized, multicenter, parallel group open label study in the Netherlands.
Accepted existing conventional rate control medication at study entry:
• beta blocker or
• calcium antagonist or
• beta blocker plus calcium antagonist or
• beta blocker plus digoxin or
• calcium antagonist plus digoxin.
Randomisation (1:1) to
Arm A (experimental arm): Addition of dronedarone 400 mg BID to the unchanged
existing conventional rate control medication.
Arm B (control arm, standard treatment): Increase of conventional rate control
medication, i.e.: dose increase of existing beta-blocker or calcium antagonist
or digoxin. At this stage the dose of no more than one drug should be increased.
In week 1 no further treatment adjustment or cardioversion.
After 1st week possibility to adjust standard treatment (beta blocker, calcium
antagonist and/or digoxin) in both arms. In arm A the dose of dronedarone shall
not be changed. Cardioversion accepted, however patient should go off study if
a 2nd cardioversion is necessary.
Duration of study: 3 months.
596 patients.
Intervention
Dronedarone or intensified standard treatment.
Study burden and risks
Risk: Adverse events of study medication.
Burden: 5 visits in 3 months. Weekly completion of questionnaire re. AF-related
symptoms. 5 bloodsamples to be taken of max 10 ml each.
Kampenringweg 45 D-E
2803 PE Gouda
Nederland
Kampenringweg 45 D-E
2803 PE Gouda
Nederland
Listed location countries
Age
Inclusion criteria
• Paroxysmal AF (according to ACC/AHA/ESC 2006 definition) with HR >80 bpm at rest despite treatment with <=2 rate control agents (i.e. beta blocker and/or calcium antagonist). Patients using digoxin are eligible.
• Documented AF in the past 24 hours.
• Treated with the following rate control medication:
- beta blocker or
- calcium antagonist or
- beta blocker plus calcium antagonist or
- beta blocker plus digoxin or
- calcium antagonist plus digoxin.
• > 45 years of age.
• Anticoagulant treatment in line with local guidelines.
Exclusion criteria
• Incapacitated patients.
• Permanent AF (according to ACC/AHA/ESC 2006 definition).
• Use of class I or III AADs in the past 3 months.
• Patients scheduled for cardioversion or pulmonary vein ablation.
• Unstable NYHA class III and all class IV HF.
• AV block grade 2 or 3.
• Known severe renal impairment (serum creatinine >180 µmol/l).
• Known severe hepatic impairment (AST, ALT >3x ULN).
• Contra-indication for dronedarone.
• Participation in a clinical drug study in the 3 months prior to inclusion.
• Women of childbearing potential, who do not use adequate contraception (in the opinion of the investigator).
• Lactating women.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-018215-53-NL |
| ClinicalTrials.gov | NCT01047566 |
| CCMO | NL31164.060.09 |