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

Primary Purpose

Atrial Fibrillation, Cerebrovascular Accident, Death, Sudden

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Amiodarone
Sotalol
Sponsored by
US Department of Veterans Affairs
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atrial Fibrillation focused on measuring amiodarone, atrial fibrillation converted to sinus rhythm, cardiac mortality, major and minor bleeds, sinus rhythm, sotalol

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients who have atrial fibrillation continuously for greater than 72 hours. Exclusion Criteria:

Sites / Locations

  • Southern Arizona VA Health Care System, Tucson
  • Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock
  • VA Central California Health Care System, Fresno
  • VA Medical Center, Loma Linda
  • VA Palo Alto Health Care System
  • VA Greater Los Angeles HCS, Sepulveda
  • VA Greater Los Angeles Healthcare System, West LA
  • VA Connecticut Health Care System (West Haven)
  • VA Medical Center, DC
  • VA Medical Center, Bay Pines
  • James A. Haley Veterans Hospital, Tampa
  • VA Medical Center, Augusta
  • Edward Hines, Jr. VA Hospital
  • VA Medical Center, Iowa City
  • VA Boston Healthcare System, Brockton Campus
  • VA Medical Center, Minneapolis
  • VA Medical Center, Kansas City MO
  • VA Medical Center, St Louis
  • New Mexico VA Health Care System, Albuquerque
  • VA Medical Center, Fargo
  • VA Medical Center, Portland
  • VA Pittsburgh Health Care System
  • VA Medical Center, Providence
  • VA Medical Center, Memphis
  • VA Medical Center
  • VA North Texas Health Care System, Dallas
  • Hunter Holmes McGuire VA Medical Center
  • Wlliam S. Middleton Memorial Veterans Hospital, Madison

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

1

2

Arm Description

Amiodarone or Sotalol

Sotalol

Outcomes

Primary Outcome Measures

Treatment failure, defined as occurrence of atrial fibrillation or flutter after day 28 or failure to convert to sinus rhythm.

Secondary Outcome Measures

Full Information

First Posted
December 29, 2000
Last Updated
June 13, 2011
Sponsor
US Department of Veterans Affairs
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1. Study Identification

Unique Protocol Identification Number
NCT00007605
Brief Title
Comparing the Effects of Amiodarone, Sotalol, and Placebo in Maintaining Sinus Rhythm in Patients With Atrial Fibrillation Converted to Sinus Rhythm
Official Title
CSP #399 - The Effects of Antiarrhythmic Therapy in Maintaining Stability of Sinus Rhythm in Atrial Fibrillation
Study Type
Interventional

2. Study Status

Record Verification Date
June 2011
Overall Recruitment Status
Completed
Study Start Date
April 1998 (undefined)
Primary Completion Date
October 2002 (Actual)
Study Completion Date
December 2003 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
US Department of Veterans Affairs

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation, Cerebrovascular Accident, Death, Sudden
Keywords
amiodarone, atrial fibrillation converted to sinus rhythm, cardiac mortality, major and minor bleeds, sinus rhythm, sotalol

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
706 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Amiodarone or Sotalol
Arm Title
2
Arm Type
Active Comparator
Arm Description
Sotalol
Intervention Type
Drug
Intervention Name(s)
Amiodarone
Intervention Description
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
Intervention Name(s)
Sotalol
Intervention Description
Patients assigned will receive 80 mg bid for 7 days and 160 mg bid thereafter.
Primary Outcome Measure Information:
Title
Treatment failure, defined as occurrence of atrial fibrillation or flutter after day 28 or failure to convert to sinus rhythm.
Time Frame
After day 28

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients who have atrial fibrillation continuously for greater than 72 hours. Exclusion Criteria:
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bramah N. Singh
Organizational Affiliation
VA Greater Los Angeles Healthcare System, West LA
Official's Role
Study Chair
Facility Information:
Facility Name
Southern Arizona VA Health Care System, Tucson
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85723
Country
United States
Facility Name
Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock
City
No. Little Rock
State/Province
Arkansas
ZIP/Postal Code
72114-1706
Country
United States
Facility Name
VA Central California Health Care System, Fresno
City
Fresno
State/Province
California
ZIP/Postal Code
93703
Country
United States
Facility Name
VA Medical Center, Loma Linda
City
Loma Linda
State/Province
California
ZIP/Postal Code
92357
Country
United States
Facility Name
VA Palo Alto Health Care System
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304-1290
Country
United States
Facility Name
VA Greater Los Angeles HCS, Sepulveda
City
Sepulveda
State/Province
California
ZIP/Postal Code
91343
Country
United States
Facility Name
VA Greater Los Angeles Healthcare System, West LA
City
West Los Angeles
State/Province
California
ZIP/Postal Code
90073
Country
United States
Facility Name
VA Connecticut Health Care System (West Haven)
City
West Haven
State/Province
Connecticut
ZIP/Postal Code
06516
Country
United States
Facility Name
VA Medical Center, DC
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20422
Country
United States
Facility Name
VA Medical Center, Bay Pines
City
Bay Pines
State/Province
Florida
ZIP/Postal Code
33708
Country
United States
Facility Name
James A. Haley Veterans Hospital, Tampa
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
VA Medical Center, Augusta
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30904
Country
United States
Facility Name
Edward Hines, Jr. VA Hospital
City
Hines
State/Province
Illinois
ZIP/Postal Code
60141-5000
Country
United States
Facility Name
VA Medical Center, Iowa City
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52246-2208
Country
United States
Facility Name
VA Boston Healthcare System, Brockton Campus
City
Brockton
State/Province
Massachusetts
ZIP/Postal Code
02301
Country
United States
Facility Name
VA Medical Center, Minneapolis
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55417
Country
United States
Facility Name
VA Medical Center, Kansas City MO
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64128
Country
United States
Facility Name
VA Medical Center, St Louis
City
St Louis
State/Province
Missouri
ZIP/Postal Code
63106
Country
United States
Facility Name
New Mexico VA Health Care System, Albuquerque
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87108-5153
Country
United States
Facility Name
VA Medical Center, Fargo
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58102
Country
United States
Facility Name
VA Medical Center, Portland
City
Portland
State/Province
Oregon
ZIP/Postal Code
97201
Country
United States
Facility Name
VA Pittsburgh Health Care System
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15240
Country
United States
Facility Name
VA Medical Center, Providence
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02908
Country
United States
Facility Name
VA Medical Center, Memphis
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38104
Country
United States
Facility Name
VA Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212-2637
Country
United States
Facility Name
VA North Texas Health Care System, Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75216
Country
United States
Facility Name
Hunter Holmes McGuire VA Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States
Facility Name
Wlliam S. Middleton Memorial Veterans Hospital, Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53705
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
12914883
Citation
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.
Results Reference
result

Learn more about this trial

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

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