Comparing the Effects of Amiodarone, Sotalol, and Placebo in Maintaining Sinus Rhythm in Patients With Atrial Fibrillation Converted to Sinus Rhythm
Information source: Department of Veterans Affairs
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Atrial Fibrillation; Cerebrovascular Accident; Death, Sudden
Intervention: Amiodarone (Drug); Sotalol (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Department of Veterans Affairs
Summary
Atrial fibrillation is the most frequently occurring cardiac arrhythmia, with 1. 0-1. 5 million
cases annually. It is a risk factor for congestive heart failure, and stroke, 75,000 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.
Clinical Details
Official title: The Effects of Antiarrhythmic Therapy in Maintaining Stability of Sinus Rhythm in Atrial Fibrillation
Study design: Treatment, Randomized, Double-Blind, Placebo Control
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
1. 0-1. 5 million cases annually. It is a risk factor for congestive heart failure, and stroke,
75,000 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 0. 05 for the set of three pairwise comparisons) will be needed for these group differences
to be statistically significant.
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
Criteria:
- Patients who have atrial fibrillation continuously for greater than 72 hours.
Locations and Contacts
Vamc - Tucson, Az, Tucson, Arizona 85723, United States
Vamc - Little Rock, Ar, Little Rock, Arkansas 72205, United States
Vamc - West Los Angeles, West Los Angeles, California 90073, United States
Vamc - Fresno, Ca, Fresno, California 93703, United States
Vamc - Loma Linda, Ca, Loma Linda, California 92354, United States
Vamc - Palo Alto, Ca, Palo Alto, California 94304, United States
Vamc - Sepulveda, Ca, Sepulveda, California 91343, United States
Vamc - West Los Angeles, Ca, West Los Angeles, California 90073, United States
Vamc - West Haven, Ct, West Haven, Connecticut 06516, United States
Vamc - Washington, Dc, Washington, District of Columbia 20422, United States
Vamc - Washington, Dc, Washington, District of Columbia 20422, United States
Vamc - Bay Pines, Fl, Bay Pines, Florida 33504, United States
Vamc - Tampa, Fl, Tampa, Florida 33612, United States
Vamc - Augusta, Ga, Augusta, Georgia 30904, United States
Vamc - Hines, Il, Hines, Illinois 60141-5000, United States
Vamc - Iowa City, Ia, Iowa City, Iowa 52242, United States
Vamc - Brockton (West Roxbury), Ma, West Roxbury, Massachusetts 02132, United States
Vamc - Minneapolis, Mn, Minneapolis, Minnesota 55417, United States
Vamc - Kansas City, Mo, Kansas City, Missouri 64128, United States
Vamc - St. Louis, Mo, St. Louis, Missouri 63106, United States
Vamc - Albuquerque, nm, Albuquerque, New Mexico 87108, United States
Vamc - Fargo, Nd, Fargo, North Dakota 58102, United States
Vamc - Portland, or, Portland, Oregon 97201, United States
Vamc - Pittsburgh, Pa, Pittsburgh, Pennsylvania 15213-2582, United States
Vamc - Pittsburgh, Pa, Pittsburgh, Pennsylvania 15240, United States
Vamc - Providence, Ri, Providence, Rhode Island 02908-4799, United States
Vamc - Memphis, Tn, Memphis, Tennessee 38104, United States
Vamc - Nashville, Tn, Nashville, Tennessee 37212, United States
Vamc - Nashville, Tn, Nashville, Tennessee 37232, United States
Vamc - Dallas, Tx, Dallas, Texas 75216, United States
Vamc - Richmond, Va, Richmond, Virginia 23249, United States
Vamc - Richmond, Va, Richmond, Virginia 23249, United States
Vamc - Madison, Wi, Madison, Wisconsin 53705, United States
Additional Information
Starting date: April 1998
Ending date: September 2002
Last updated: June 23, 2005
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