Ignite Creation Date:
2024-05-05 @ 10:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00007605
Status:
COMPLETED
Last Update Posted:
2011-06-15
First Post:
2000-12-29
Brief Title:
Comparing the Effects of Amiodarone Sotalol and Placebo in Maintaining Sinus Rhythm in Patients With Atrial Fibrillation Converted to Sinus Rhythm
Sponsor:
US Department of Veterans Affairs
Organization:
VA Office of Research and Development
Study Overview
Official Title:
CSP 399 - The Effects of Antiarrhythmic Therapy in Maintaining Stability of Sinus Rhythm in Atrial Fibrillation
Status:
COMPLETED
Status Verified Date:
2011-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Atrial fibrillation is the most frequently occurring cardiac arrhythmia with 10-15 million cases annually It is a risk factor for congestive heart failure and stroke 75000 cases of the latter occurring annually in patients with atrial fibrillation The safety of the most widely used antiarrhythmic agent for this group of patients quinidine has been called into question This study seeks to determine whether two other agents amiodarone and sotalol are safe and effective treatments for patients with atrial fibrillation
Detailed Description:
Primary Hypothesis The primary objective is to compare the effects of amiodarone sotalol and placebo in maintaining sinus rhythm in patients with atrial fibrillation converted to sinus rhythm
Secondary Hypotheses To compare the three therapies in regard to 1 Frequency of episodes of major and minor strokes 2 Frequency of episodes of major and minor bleeds 3 Frequency of sudden death cardiac mortality and total mortality 4 Frequency of life-threatening pro-arrhythmic reactions 5 Frequency of episodes of congestive heart failure 6 Frequency of side effects necessitating discontinuation of therapy 7 Frequency and mean duration of hospitalization directly related to atrial fibrillation or flutter 8 Mean change in maximal exercise capacity on treadmill during atrial fibrillation or flutter versus sinus rhythm 9 Time to the development of sinus rhythm from randomization to day 28 of the study 10 Mean duration of the intervals between occurrences of atrial fibrillation or flutter after day 28 11 The mean ventricular response documented on electrocardiogram ECG recordings during occurrences of atrial fibrillation or flutter after day 28 12 Changes in health-related quality of life as measured by the SF-36 and an atrial fibrillation quality of life questionnaire 13 Time to first occurrence of atrial fibrillation or flutter after day 28 or cessation of treatment due to adverse drug reactions after randomization
Intervention Patients are randomized to amiodarone 400mg bid for 14 days 400mg qam and d200mg qhs for 14 days 300mg qd for 48 weeks then 200mg qd sotalol 80mg bid for 7 days and 160mg bid thereafter or placebo
Primary Outcomes The time from day 28 of randomization to first occurrence of atrial fibrillation or flutter Failure time will be set at 0 days for patients who fail to cardiovert at day 28
Study Abstract Atrial fibrillation is the most frequently occurring cardiac arrhythmia with 10-15 million cases annually It is a risk factor for congestive heart failure and stroke 75000 cases of the latter occurring annually in patients with atrial fibrillation The safety of the most widely used antiarrhythmic agent for this group of patients quinidine has been called into question This study seeks to determine whether two other agents amiodarone and sotalol are safe and effective treatments for patients with atrial fibrillation All patients will have atrial fibrillation continuously for greater than 72 hours Background medications will include warfarin for anticoagulation and digoxin plus diltiazem or verapamil for heart rate control If warfarin is contraindicated left atrial thrombus must be excluded by transesophageal echo TEE and aspirin 325 mg QD may be used Patients will be randomly assigned to receive sotalol 80 mg bid for 7 days and 160 mg bid thereafter amiodarone 400 mg bid for 14 days 400 mg qam and 200 mg qhs for 14 days 300 mg qd for 48 weeks then 200 mg qd or placebo Treatment assignment will be stratified by participating hospital whether the patient has ischemic heart disease and whether the patient is symptomatic After randomization patients will stay on drugs for rate control until sinus rhythm is restored and on anticoagulation until two months after sinus rhythm has been restored After four weeks patients remaining in atrial fibrillation will undergo DC cardioversion Those patients not on warfarin must undergo another TEE within 48 hours prior to cardioversion Patients will have their heart rhythm monitored transtelephonically every week and occurrences of atrial fibrillation or flutter will be documented twice within 24 hours In the case of documented atrial fibrillation or flutter occurrence the patient will be re-anticoagulated and at appropriate time subjected to a further DC cardioversion to restore sinus rhythm Patients in sinus rhythm will be followed until the end of the study Patients relapsing into AF will be followed a minimum of one year or until relapse whichever is later Assuming 35 of patients on placebo 50 on sotalol and 60 on amiodarone remain in normal sinus rhythm at the end of one year a sample size of 706 patients 279 on amiodarone 279 on sotalol and 148 on placebo 85 power and two-sided overall alpha level of 005 for the set of three pairwise comparisons will be needed for these group differences to be statistically significant
Secondary Hypotheses To compare the three therapies in regard to 1 Frequency of episodes of major and minor strokes 2 Frequency of episodes of major and minor bleeds 3 Frequency of sudden death cardiac mortality and total mortality 4 Frequency of life-threatening pro-arrhythmic reactions 5 Frequency of episodes of congestive heart failure 6 Frequency of side effects necessitating discontinuation of therapy 7 Frequency and mean duration of hospitalization directly related to atrial fibrillation or flutter 8 Mean change in maximal exercise capacity on treadmill during atrial fibrillation or flutter versus sinus rhythm 9 Time to the development of sinus rhythm from randomization to day 28 of the study 10 Mean duration of the intervals between occurrences of atrial fibrillation or flutter after day 28 11 The mean ventricular response documented on electrocardiogram ECG recordings during occurrences of atrial fibrillation or flutter after day 28 12 Changes in health-related quality of life as measured by the SF-36 and an atrial fibrillation quality of life questionnaire 13 Time to first occurrence of atrial fibrillation or flutter after day 28 or cessation of treatment due to adverse drug reactions after randomization
Intervention Patients are randomized to amiodarone 400mg bid for 14 days 400mg qam and d200mg qhs for 14 days 300mg qd for 48 weeks then 200mg qd sotalol 80mg bid for 7 days and 160mg bid thereafter or placebo
Primary Outcomes The time from day 28 of randomization to first occurrence of atrial fibrillation or flutter Failure time will be set at 0 days for patients who fail to cardiovert at day 28
Study Abstract Atrial fibrillation is the most frequently occurring cardiac arrhythmia with 10-15 million cases annually It is a risk factor for congestive heart failure and stroke 75000 cases of the latter occurring annually in patients with atrial fibrillation The safety of the most widely used antiarrhythmic agent for this group of patients quinidine has been called into question This study seeks to determine whether two other agents amiodarone and sotalol are safe and effective treatments for patients with atrial fibrillation All patients will have atrial fibrillation continuously for greater than 72 hours Background medications will include warfarin for anticoagulation and digoxin plus diltiazem or verapamil for heart rate control If warfarin is contraindicated left atrial thrombus must be excluded by transesophageal echo TEE and aspirin 325 mg QD may be used Patients will be randomly assigned to receive sotalol 80 mg bid for 7 days and 160 mg bid thereafter amiodarone 400 mg bid for 14 days 400 mg qam and 200 mg qhs for 14 days 300 mg qd for 48 weeks then 200 mg qd or placebo Treatment assignment will be stratified by participating hospital whether the patient has ischemic heart disease and whether the patient is symptomatic After randomization patients will stay on drugs for rate control until sinus rhythm is restored and on anticoagulation until two months after sinus rhythm has been restored After four weeks patients remaining in atrial fibrillation will undergo DC cardioversion Those patients not on warfarin must undergo another TEE within 48 hours prior to cardioversion Patients will have their heart rhythm monitored transtelephonically every week and occurrences of atrial fibrillation or flutter will be documented twice within 24 hours In the case of documented atrial fibrillation or flutter occurrence the patient will be re-anticoagulated and at appropriate time subjected to a further DC cardioversion to restore sinus rhythm Patients in sinus rhythm will be followed until the end of the study Patients relapsing into AF will be followed a minimum of one year or until relapse whichever is later Assuming 35 of patients on placebo 50 on sotalol and 60 on amiodarone remain in normal sinus rhythm at the end of one year a sample size of 706 patients 279 on amiodarone 279 on sotalol and 148 on placebo 85 power and two-sided overall alpha level of 005 for the set of three pairwise comparisons will be needed for these group differences to be statistically significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None