Dronedarone in Pacemakers Patients With Paroxysmal Atrial Fibrillation

Study Overview
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Brief Summary
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The purpose of this study is to accurately investigate the efficacy of dronedarone in maintaining sinus rhythm and decreasing AFB in patients with paroxysmal atrial fibrillation as compared with placebo. This has never previously been performed using pacemaker Holter monitoring which provides detailed information of atrial arrhythmia patterns the entire study period. Additionally detailed patient symptom self assessment and questionnaires will be collected. The study design will be double blinded crossover with each phase lasting 3 months.

Detailed Description
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The study is planned to commence in March 2010 after obtaining Ethics Committee approval. Patients will be randomised to a three month course of dronedarone or placebo. 1:1 double blinded randomisation will be undertaken. At three months, after a one week washout period, the patients will cross-over treatment groups. To achieve a power of 0.8 with a type one error rate 5% detecting a relative difference of 10% primary outcomes the study will require 42 patients. 50 patients in total will be enrolled in the study. The study will take place at Eastbourne District General Hospital. The study duration per patient is 7 months. The overall study duration will be 1 year. STUDY OVERVIEW Appropriate patients with DDDRP pacemakers with an AF burden of 1-50% detected on pacemaker holters will be identified from the pacing clinic list and the Cardiology Outpatient Department at the Eastbourne District General Hospital. They will be invited to take part after a verbal explanation of the study has been given. If agreement is obtained each patient will be given the Patient Information Sheet and allowed time to consider their participation in the study and to ask relevant questions. If they are still in agreement they will be asked to sign the Patient Consent Form. Initially, all patients will have all baseline parameters assessed. All patients will stop taking their anti-arrhythmic drugs for a period of one week. Patients will then have a three month course of either dronedarone or placebo according to randomisation in a double blinded fashion. Randomisation will be performed by use of random number tables. At three months data will be collected from patient questionnaires and pacemaker Holter. There will be a one week washout period at this time. Patients will then cross-over to dronedarone or placebo for a three month period. Data from patient questionnaires and pacemaker Holters will be collected at three months after cross-over. Patients will then undergo a further week washout period before re-initiating their original anti-arrhythmic therapy.

Official Title
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Dronedarone in Pacemaker Patients With Paroxysmal Atrial Fibrillation

Conditions
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Paroxysmal Atrial Fibrillation

Intervention / Treatment
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* Drug: Dronedarone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with paroxysmal atrial fibrillation (AF burden 1-50% as defined by DDDRP PPM) during the 3 months prior to induction to the study. Patients who have had DDDRP pacemaker implanted for a primary or secondary indication. Patients must be on warfarin. Patients must be over 18 years old. Patients give informed consent form prior to participating in this study. Exclusion Criteria: Current or previous treatment with amiodarone. Patient is suffering with unstable angina in last 1 week. Patient has had a myocardial infarction within last 2 months. Patient is expecting or has had major cardiac surgery within last 2 months. Patient is participating in a conflicting study. Patient is mentally incapacitated and cannot consent or comply with follow-up. Patient has NYHA class III/ IV heart failure. Pregnancy. Patient suffers with other cardiac rhythm disorders. Recent coronary artery intervention or other factors suggesting clinical instability (ECG, clinical or laboratory findings). GFR < 30mls/min.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dronedarone<br>Patients will receive 400 mg of dronedarone per day for 3 months. | Drug: Dronedarone<br>* 400mg orally once per day for 3 months<br>* Other names: Multaq;|
| Placebo Comparator: Placebo<br>Patients will receive a placebo tablet once per day for 3 months. AF burden and other parameters described will be monitored from the participants permanent pacemaker. Participants will also be asked to fill out symptom diaries and questionaires. | Drug: Placebo<br>* 1 tablet once per day for 3 months. The tablet will appear identical to the active dronedarone tablet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To accurately assess, by the use of long term beat to beat pacemaker Holter monitoring, the effect of of dronedarone upon AF burden. |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To accurately assess the number of AF episodes, AF frequency and average duration of sinus rhythm. |  | 3 months | 
| To assess differences in patient experience of dronedarone and placebo therapies by means of questionnaires. |  | 3 months | 
| Quality of life measures - SF-36, visual analogue scores, symptom assessment scores. |  | 3 months | 
| Comparison of side effects and major adverse cardiac events. |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PAF, AF, Dronedarone, AF Burden, AFB, PPM, Permanent Pacemaker, Atrial Fibrillation Burden in Paroxysmal Atrial Fibrillation