Comparing the Effects of Amiodarone, Sotalol, and Placebo in Maintaining Sinus Rhythm in Patients With Atrial Fibrillation Converted to Sinus Rhythm

Atrial Fibrillation Clinical Trial

Official title:

CSP #399 - The Effects of Antiarrhythmic Therapy in Maintaining Stability of Sinus Rhythm in Atrial Fibrillation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00007605
• Other study ID #: 399
• Status: Completed
• Phase: Phase 3
• First received: December 29, 2000
• Last updated: June 13, 2011
• Start date: April 1998
• Est. completion date: December 2003

Study information

• Verified date: June 2011
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 706
• Est. completion date: December 2003
• Est. primary completion date: October 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients who have atrial fibrillation continuously for greater than 72 hours.

Exclusion Criteria:

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation
• Cerebrovascular Accident
• Death, Sudden
• Stroke

Intervention

Drug:
• Amiodarone
Patients assigned will receive 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.
• Sotalol
Patients assigned will receive 80 mg bid for 7 days and 160 mg bid thereafter.

Locations

Country	Name	City	State
United States	New Mexico VA Health Care System, Albuquerque	Albuquerque	New Mexico
United States	VA Medical Center, Augusta	Augusta	Georgia
United States	VA Medical Center, Bay Pines	Bay Pines	Florida
United States	VA Boston Healthcare System, Brockton Campus	Brockton	Massachusetts
United States	VA North Texas Health Care System, Dallas	Dallas	Texas
United States	VA Medical Center, Fargo	Fargo	North Dakota
United States	VA Central California Health Care System, Fresno	Fresno	California
United States	Edward Hines, Jr. VA Hospital	Hines	Illinois
United States	VA Medical Center, Iowa City	Iowa City	Iowa
United States	VA Medical Center, Kansas City MO	Kansas City	Missouri
United States	VA Medical Center, Loma Linda	Loma Linda	California
United States	Wlliam S. Middleton Memorial Veterans Hospital, Madison	Madison	Wisconsin
United States	VA Medical Center, Memphis	Memphis	Tennessee
United States	VA Medical Center, Minneapolis	Minneapolis	Minnesota
United States	VA Medical Center	Nashville	Tennessee
United States	Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock	No. Little Rock	Arkansas
United States	VA Palo Alto Health Care System	Palo Alto	California
United States	VA Pittsburgh Health Care System	Pittsburgh	Pennsylvania
United States	VA Medical Center, Portland	Portland	Oregon
United States	VA Medical Center, Providence	Providence	Rhode Island
United States	Hunter Holmes McGuire VA Medical Center	Richmond	Virginia
United States	VA Greater Los Angeles HCS, Sepulveda	Sepulveda	California
United States	VA Medical Center, St Louis	St Louis	Missouri
United States	James A. Haley Veterans Hospital, Tampa	Tampa	Florida
United States	Southern Arizona VA Health Care System, Tucson	Tucson	Arizona
United States	VA Medical Center, DC	Washington	District of Columbia
United States	VA Connecticut Health Care System (West Haven)	West Haven	Connecticut
United States	VA Greater Los Angeles Healthcare System, West LA	West Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

References & Publications (1)

Singh SN, Singh BN, Reda DJ, Fye CL, Ezekowitz MD, Fletcher RD, Sharma SC, Atwood JE, Jacobson AK, Lewis HD Jr, Antman EM, Falk RH, Lopez B, Tang XC. Comparison of sotalol versus amiodarone in maintaining stability of sinus rhythm in patients with atrial — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment failure, defined as occurrence of atrial fibrillation or flutter after day 28 or failure to convert to sinus rhythm.		After day 28	No