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

NCT ID: NCT00007605

Last Updated: 2011-06-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

706 participants

Study Classification

INTERVENTIONAL

Study Start Date

1998-04-30

Study Completion Date

2003-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Atrial Fibrillation Cerebrovascular Accident Death, Sudden

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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1

Amiodarone or Sotalol

Group Type ACTIVE_COMPARATOR

Amiodarone

Intervention Type DRUG

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.

2

Sotalol

Group Type ACTIVE_COMPARATOR

Sotalol

Intervention Type DRUG

Patients assigned will receive 80 mg bid for 7 days and 160 mg bid thereafter.

Interventions

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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.

Intervention Type DRUG

Sotalol

Patients assigned will receive 80 mg bid for 7 days and 160 mg bid thereafter.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients who have atrial fibrillation continuously for greater than 72 hours.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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US Department of Veterans Affairs

FED

Sponsor Role lead

Responsible Party

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Department of Veterans Affairs

Principal Investigators

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Bramah N. Singh

Role: STUDY_CHAIR

VA Greater Los Angeles Healthcare System, West LA

Locations

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Southern Arizona VA Health Care System, Tucson

Tucson, Arizona, United States

Site Status

Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock

No. Little Rock, Arkansas, United States

Site Status

VA Central California Health Care System, Fresno

Fresno, California, United States

Site Status

VA Medical Center, Loma Linda

Loma Linda, California, United States

Site Status

VA Palo Alto Health Care System

Palo Alto, California, United States

Site Status

VA Greater Los Angeles HCS, Sepulveda

Sepulveda, California, United States

Site Status

VA Greater Los Angeles Healthcare System, West LA

West Los Angeles, California, United States

Site Status

VA Connecticut Health Care System (West Haven)

West Haven, Connecticut, United States

Site Status

VA Medical Center, DC

Washington D.C., District of Columbia, United States

Site Status

VA Medical Center, Bay Pines

Bay Pines, Florida, United States

Site Status

James A. Haley Veterans Hospital, Tampa

Tampa, Florida, United States

Site Status

VA Medical Center, Augusta

Augusta, Georgia, United States

Site Status

Edward Hines, Jr. VA Hospital

Hines, Illinois, United States

Site Status

VA Medical Center, Iowa City

Iowa City, Iowa, United States

Site Status

VA Boston Healthcare System, Brockton Campus

Brockton, Massachusetts, United States

Site Status

VA Medical Center, Minneapolis

Minneapolis, Minnesota, United States

Site Status

VA Medical Center, Kansas City MO

Kansas City, Missouri, United States

Site Status

VA Medical Center, St Louis

St Louis, Missouri, United States

Site Status

New Mexico VA Health Care System, Albuquerque

Albuquerque, New Mexico, United States

Site Status

VA Medical Center, Fargo

Fargo, North Dakota, United States

Site Status

VA Medical Center, Portland

Portland, Oregon, United States

Site Status

VA Pittsburgh Health Care System

Pittsburgh, Pennsylvania, United States

Site Status

VA Medical Center, Providence

Providence, Rhode Island, United States

Site Status

VA Medical Center, Memphis

Memphis, Tennessee, United States

Site Status

VA Medical Center

Nashville, Tennessee, United States

Site Status

VA North Texas Health Care System, Dallas

Dallas, Texas, United States

Site Status

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, United States

Site Status

Wlliam S. Middleton Memorial Veterans Hospital, Madison

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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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 fibrillation (Sotalol-Amiodarone Fibrillation Efficacy Trial [Safe-T]). Am J Cardiol. 2003 Aug 15;92(4):468-72. doi: 10.1016/s0002-9149(03)00671-4.

Reference Type RESULT
PMID: 12914883 (View on PubMed)

Other Identifiers

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399

Identifier Type: -

Identifier Source: org_study_id

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