Ignite Creation Date:
2024-05-05 @ 11:22 AM
Last Modification Date:
2024-10-26 @ 9:01 AM
Study NCT ID:
NCT00000556
Status:
COMPLETED
Last Update Posted:
2016-03-25
First Post:
1999-10-27
Brief Title:
Atrial Fibrillation Follow-up Investigation of Rhythm Management AFFIRM
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2005-11
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:
To compare two standard treatment strategies for atrial fibrillation ventricular rate control and anticoagulation vs rhythm control and anticoagulation
Detailed Description:
BACKGROUND
Atrial fibrillation is an extremely common and increasingly prevalent cardiac arrhythmia particularly in the elderly and is an important risk factor for stroke Management of atrial fibrillation remains controversial and although antiarrhythmic drugs are widely used for this condition clinical studies to support their use are meager Management of atrial fibrillation has at least three components restoration and maintenance of sinus rhythm heart rate control when maintenance of sinus rhythm or when cardioversion is not attempted or impossible and anticoagulation The first component of management uses antiarrhythmic drugs and the second uses a different group of antiarrhythmic drugs and catheter ablation The third is anticoagulant therapy for patients in whom normal sinus rhythm cannot be maintained or in whom cardioversion is not attempted
The initiative was developed by staff of the Clinical Trials Branch and the NHLBI Working Group on Atrial Fibrillation which met in Bethesda in April 1993 The initiative was given concept clearance by the February 1994 National Heart Lung and Blood Advisory Council The Request for Proposals was released in May 1994
DESIGN NARRATIVE
A randomized multicenter trial The trial enrolled only patients with atrial fibrillation who were at high risk for stroke that is over 65 years of age or less than 65 and with one or more other risk factors for stroke such as systemic hypertension diabetes mellitus congestive heart failure transient ischemic attack prior cerebral vascular accident High risk patients were treated with the anticoagulant warfarin Cardioversion electrical or pharmacologic might have been attempted before randomization but if it was unsuccessful the patient was excluded from further consideration for randomization Normal sinus rhythm must have persisted for one hour or greater after cardioversion to qualify as successful cardioversion Patients were randomly assigned to treatment groups which included maintenance of sinus rhythm or heart rate control Both treatment groups had two steps
In the maintenance of sinus rhythm group the choice of drugs was left to the primary treating physician to be chosen from amiodarone sotalol propafenone flecainide quinidine moricizine disopyramide procainamide and combinations of these drugs Atrioventricular nodal blocking drugs were also administered unless contraindicated The major substudy for AFFIRM randomized initial drug choice among amiodarone sotalol and class I drugs Prior drugs which were ineffective or poorly tolerated were not repeated There were various drug exclusions depending on the patients condition Patients in the maintenance of sinus rhythm group had multiple cardioversions as needed If there was treatment failure or intolerance after two or more pharmacologic trials patients were considered for innovative therapy in Step II In Step II two maintenance doses of amiodarone were included a low dose of 100 to 200 mgday and a normal dose of 300 to 400 mgday Each dose of amiodarone was considered to be a single drug trial so that patients who received treatment with amiodarone at both dosage levels were considered to have had two drug trials It was not mandatory that Step II therapies be applied in any individual patient The following innovative Step II therapies were approved for use in the study 1 ablation of an atrial focus in patients with type I atrial flutter if it was clinically documented that the atrial flutter led to atrial fibrillation 2 atrial pacing alone with or without documented bradycardia 3 atrial pacing and antiarrhythmic drugs with either single site or multiple site atrial pacing and 4 surgical maze or atrial isolation procedures at selected centers Catheter-based ablative procedures such as those attempting to mimic the maze procedure were not approved in this study Implanted atrial cardioverter defibrillators were also not approved All therapy was periodically reviewed and subject to modification by the Steering Committee with concurrence by the DSMB and the NHLBI In the event that sinus rhythm was not maintainable by any treatment patients crossed over to rate control and anticoagulation
The heart rate control arm used heart rate as the therapeutic target rather than dose of medications Drug dosage was adjusted to achieve target heart rates During atrial fibrillation heart rate was assessed both at rest and during activity at each clinic visit The pharmacologic therapies approved for use in this arm included beta blockers verapamil diltiazem digoxin or combinations of these drugs When Step I pharmacologic therapies failed after two or more drug trials the treating physician could select an approved Step II innovative therapy The two innovative therapies approved for use with the heart rate control arm were 1 atrioventricular node modification by catheter ablation with or without placement of a pacemaker with or without continued drugs to slow atrioventricular node conduction and 2 total atrioventricular junctional ablation and placement of a pacemaker
The primary endpoint by which the two strategies were compared was total mortality analyzed by intention-to-treat Secondary endpoints were composite end points total mortality disabling intracranial bleed stroke disabling anoxic encephalopathy cardiac arrest major noncentral nervous system bleed cost of therapy and quality of life Follow-up was a minimum of two years and an average of 35 years Recruitment and intervention extended from November 1995 through October 1999 with 4060 patients enrolled by 213 sites
Atrial fibrillation is an extremely common and increasingly prevalent cardiac arrhythmia particularly in the elderly and is an important risk factor for stroke Management of atrial fibrillation remains controversial and although antiarrhythmic drugs are widely used for this condition clinical studies to support their use are meager Management of atrial fibrillation has at least three components restoration and maintenance of sinus rhythm heart rate control when maintenance of sinus rhythm or when cardioversion is not attempted or impossible and anticoagulation The first component of management uses antiarrhythmic drugs and the second uses a different group of antiarrhythmic drugs and catheter ablation The third is anticoagulant therapy for patients in whom normal sinus rhythm cannot be maintained or in whom cardioversion is not attempted
The initiative was developed by staff of the Clinical Trials Branch and the NHLBI Working Group on Atrial Fibrillation which met in Bethesda in April 1993 The initiative was given concept clearance by the February 1994 National Heart Lung and Blood Advisory Council The Request for Proposals was released in May 1994
DESIGN NARRATIVE
A randomized multicenter trial The trial enrolled only patients with atrial fibrillation who were at high risk for stroke that is over 65 years of age or less than 65 and with one or more other risk factors for stroke such as systemic hypertension diabetes mellitus congestive heart failure transient ischemic attack prior cerebral vascular accident High risk patients were treated with the anticoagulant warfarin Cardioversion electrical or pharmacologic might have been attempted before randomization but if it was unsuccessful the patient was excluded from further consideration for randomization Normal sinus rhythm must have persisted for one hour or greater after cardioversion to qualify as successful cardioversion Patients were randomly assigned to treatment groups which included maintenance of sinus rhythm or heart rate control Both treatment groups had two steps
In the maintenance of sinus rhythm group the choice of drugs was left to the primary treating physician to be chosen from amiodarone sotalol propafenone flecainide quinidine moricizine disopyramide procainamide and combinations of these drugs Atrioventricular nodal blocking drugs were also administered unless contraindicated The major substudy for AFFIRM randomized initial drug choice among amiodarone sotalol and class I drugs Prior drugs which were ineffective or poorly tolerated were not repeated There were various drug exclusions depending on the patients condition Patients in the maintenance of sinus rhythm group had multiple cardioversions as needed If there was treatment failure or intolerance after two or more pharmacologic trials patients were considered for innovative therapy in Step II In Step II two maintenance doses of amiodarone were included a low dose of 100 to 200 mgday and a normal dose of 300 to 400 mgday Each dose of amiodarone was considered to be a single drug trial so that patients who received treatment with amiodarone at both dosage levels were considered to have had two drug trials It was not mandatory that Step II therapies be applied in any individual patient The following innovative Step II therapies were approved for use in the study 1 ablation of an atrial focus in patients with type I atrial flutter if it was clinically documented that the atrial flutter led to atrial fibrillation 2 atrial pacing alone with or without documented bradycardia 3 atrial pacing and antiarrhythmic drugs with either single site or multiple site atrial pacing and 4 surgical maze or atrial isolation procedures at selected centers Catheter-based ablative procedures such as those attempting to mimic the maze procedure were not approved in this study Implanted atrial cardioverter defibrillators were also not approved All therapy was periodically reviewed and subject to modification by the Steering Committee with concurrence by the DSMB and the NHLBI In the event that sinus rhythm was not maintainable by any treatment patients crossed over to rate control and anticoagulation
The heart rate control arm used heart rate as the therapeutic target rather than dose of medications Drug dosage was adjusted to achieve target heart rates During atrial fibrillation heart rate was assessed both at rest and during activity at each clinic visit The pharmacologic therapies approved for use in this arm included beta blockers verapamil diltiazem digoxin or combinations of these drugs When Step I pharmacologic therapies failed after two or more drug trials the treating physician could select an approved Step II innovative therapy The two innovative therapies approved for use with the heart rate control arm were 1 atrioventricular node modification by catheter ablation with or without placement of a pacemaker with or without continued drugs to slow atrioventricular node conduction and 2 total atrioventricular junctional ablation and placement of a pacemaker
The primary endpoint by which the two strategies were compared was total mortality analyzed by intention-to-treat Secondary endpoints were composite end points total mortality disabling intracranial bleed stroke disabling anoxic encephalopathy cardiac arrest major noncentral nervous system bleed cost of therapy and quality of life Follow-up was a minimum of two years and an average of 35 years Recruitment and intervention extended from November 1995 through October 1999 with 4060 patients enrolled by 213 sites
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?: