- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00597077
Atrial Fibrillation and Congestive Heart Failure Trial
Atrial Fibrillation and Congestive Heart Failure (AF-CHF)Trial
Study Overview
Status
Conditions
Detailed Description
Congestive heart failure (CHF) and atrial fibrillation (AF) are two important and growing problems in medicine and cardiology. Both conditions often co-exist and complicate each other's management. Two therapeutic strategies are available for patients with AF and CHF: the first aims at restoring and maintaining sinus rhythm, whereas, the second focuses exclusively on optimizing ventricular rate. The primary objective of the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial is to compare these two widely-used treatment strategies with respect to cardiovascular mortality.
Hypothesis: Restoring and maintaining sinus rhythm reduces cardiovascular mortality compared to a rate control treatment strategy in patients with AF and CHF.
Rationale: Despite new therapeutic interventions, the prognosis of heart failure patients remains grim with 5-year survival rates usually less than 50%. In most recent, large CHF trials, AF has been reported to be independently associated with increased mortality. Non-randomized observations also suggest that patients with AF in the setting of CHF have a greater tendency to revert to sinus rhythm during amiodarone therapy or with newer class III antiarrhythmic agents and that those who maintain a normal rhythm have a better prognosis. There is a need to determine whether a treatment strategy that attempts to maintain sinus rhythm will have a beneficial impact on cardiovascular mortality in CHF patients. This hypothesis has never been tested in a prospective, controlled, adequately-powered randomized trial.
Research Plan: AF-CHF is a prospective, multicentre clinical trial (100 centres in Canada, the USA, and Europe), that will randomize 1,450 NYHA class II-IV CHF patients with left ventricular ejection fraction >/=35% (NYHA class I patients with prior hospitalization for CHF or ejection fraction </=25% are also eligible) and a history of significant AF (ECG documentation of either one episode lasting >/=6 hours within the past 6 months, or an episode lasting >/=10 minutes within the past 6 months in a patient with prior electrical cardioversion for AF) to one of two treatment strategies: 1) rhythm control with the use of electrical cardioversion if needed combined with antiarrhythmic drug therapy (amiodarone or other class III agents), and additional non-pharmacologic therapy in resistant patients, 2) rate control with the use of drugs (mainly beta-blockers plus digoxin) and/or pacemaker and AV nodal catheter ablation if necessary. The enrollment period will be completed within 2 years with a minimum follow-up of 2 years. Both groups will receive optimal CHF management with ACE inhibitors and beta-blockers. Cardiovascular mortality will be the primary endpoint of the trial. The intention-to-treat approach will be the primary method of analysis. Secondary outcomes are total mortality, hospitalization, stroke, cost of therapy and quality of life. From recent trial data, we anticipate a 18.75% 2-year cardiovascular mortality in the rate control arm and a 25% reduction in cardiovascular mortality in the rhythm control group. Assuming a 2% loss to follow-up, a two-sided alpha level of 0.05 and an annual accrual rate of 750 patients, we calculate that 722 patients per group (rounded total number of 1,450 patients) will be necessary to achieve a power of 0.80 when performing a log-rank test. The Research Centre of the Montreal Heart Institute will be the Coordinating and Methods Centre.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Quebec
-
Montreal, Quebec, Canada, h1s2j2
- Montreal Heart Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Left ventricular ejection fraction </=35% as measured by nuclear imaging, echocardiography, or cardiac angiography within 6 months preceding enrollment. If the patient has had a myocardial infarction or heart surgery during this period, the ejection fraction must be remeasured.
- Symptomatic CHF (NYHA class II-IV) at some time during the 6 months before randomization, despite therapy with an ACE inhibitor (however, patients who do not tolerate an ACE inhibitor are eligible). Asymptomatic patients (NYHA class I) with either a prior hospitalization for CHF during the 6 months before randomization or with a left ventricular ejection fraction of </=25% are also eligible.
History of significant AF, defined as either:
- one episode lasting >/=6 hours (duration of AF will be determined by history), within the past 6 months with electrocardiographic confirmation; or
- an episode lasting >/=10 minutes (by history) within the past 6 months with electrocardiographic confirmation in a patient with a prior electrical cardioversion for AF.
- In the opinion of the clinical investigator, the patient must be eligible for long-term treatment with either treatment strategy of AF.
Exclusion Criteria:
- AF is known to be present and uninterrupted for more than 12 months prior to randomization. However, if such a patient is cardioverted and maintained in sinus rhythm for >/=24 hours, he or she becomes eligible.
- Reversible cause of AF such as acute pericarditis, pulmonary embolism, hyperthyroidism, alcohol intoxication.
- AF occurring and not persisting beyond 10 days of surgery or myocardial infarction.
- Reversible cause of CHF such as severe aortic or mitral stenosis and tachycardia-induced cardiomyopathy.
- Decompensated CHF within 48 hours of randomization.
- Antiarrhythmic drugs other than calcium channel blockers, beta-blockers or digoxin required for other arrhythmias or other indications.
- More than 7 days of amiodarone therapy within the last month prior to randomization.
- Second or third degree AV block, sinus pause >3 seconds, resting heart rate <50 bpm without a permanent pacemaker.
- History of drug-induced Torsades de Pointes or congenital long QT syndrome.
- Prior AV nodal ablation or Maze surgery.
- Probable cardiac transplantation in the next 6 months.
- Chronic renal failure requiring dialysis.
- Women of child-bearing potential and not on a reliable method of birth control.
- Geographic or social factors, drug or alcohol abuse making follow-up or compliance difficult.
- Other noncardiovascular medical condition (such as cancer) making 1 year survival unlikely.
- Less than 18 years of age.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Rate control
|
Rate vs rhythm control strategies for atrial fibrillation
|
Active Comparator: Rhythm control
|
rate vs rhythm control strategies in atrial fibrillation
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
cardiovascular death
Time Frame: Minimum of 2 years and a maximum of 6 years
|
Minimum of 2 years and a maximum of 6 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Total mortality
Time Frame: Minimun of 2 years and a maxiumum of 6 years
|
Minimun of 2 years and a maxiumum of 6 years
|
Stroke
Time Frame: Minimum of 2 years and a maximum of 6 years
|
Minimum of 2 years and a maximum of 6 years
|
Worsening CHF
Time Frame: Minimum of 2 years and maximum of 6 years
|
Minimum of 2 years and maximum of 6 years
|
Hospitalization
Time Frame: Minumum of 2 years and maximum of 6 years
|
Minumum of 2 years and maximum of 6 years
|
Composite endpoint of CV death and worsening CHF
Time Frame: Minimum of 2 years and a maximum of 6 years
|
Minimum of 2 years and a maximum of 6 years
|
Composite endpoint of CV death, stroke and worsening CHF
Time Frame: Minimum of 2 years and a maximum of 6 years
|
Minimum of 2 years and a maximum of 6 years
|
Quality of life/depression
Time Frame: Minimum of 2 years and a maximum of 6 years
|
Minimum of 2 years and a maximum of 6 years
|
Cost of therapy
Time Frame: Minimum of 2 years and a maximum of 6 years
|
Minimum of 2 years and a maximum of 6 years
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Denis Roy, Montreal Heart Institute
Publications and helpful links
General Publications
- O'Meara E, Khairy P, Blanchet MC, de Denus S, Pedersen OD, Levesque S, Talajic M, Ducharme A, White M, Racine N, Rouleau JL, Tardif JC, Roy D; AF-CHF investigators. Mineralocorticoid receptor antagonists and cardiovascular mortality in patients with atrial fibrillation and left ventricular dysfunction: insights from the Atrial Fibrillation and Congestive Heart Failure Trial. Circ Heart Fail. 2012 Sep 1;5(5):586-93. doi: 10.1161/CIRCHEARTFAILURE.111.965160. Epub 2012 Jul 12.
- Frasure-Smith N, Lesperance F, Habra M, Talajic M, Khairy P, Dorian P, Roy D; Atrial Fibrillation and Congestive Heart Failure Investigators. Elevated depression symptoms predict long-term cardiovascular mortality in patients with atrial fibrillation and heart failure. Circulation. 2009 Jul 14;120(2):134-40, 3p following 140. doi: 10.1161/CIRCULATIONAHA.109.851675. Epub 2009 Jun 29.
- Roy D, Talajic M, Nattel S, Wyse DG, Dorian P, Lee KL, Bourassa MG, Arnold JM, Buxton AE, Camm AJ, Connolly SJ, Dubuc M, Ducharme A, Guerra PG, Hohnloser SH, Lambert J, Le Heuzey JY, O'Hara G, Pedersen OD, Rouleau JL, Singh BN, Stevenson LW, Stevenson WG, Thibault B, Waldo AL; Atrial Fibrillation and Congestive Heart Failure Investigators. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008 Jun 19;358(25):2667-77. doi: 10.1056/NEJMoa0708789.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 41552
- ISRCTN84858671
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Atrial Fibrillation
-
Ablacon, Inc.CompletedArrhythmias, Cardiac | Atrial Fibrillation, Persistent | Persistent Atrial Fibrillation | Longstanding Persistent Atrial FibrillationGermany
-
Ablacon, Inc.RecruitingAtrial Fibrillation | Arrhythmias, Cardiac | Arrhythmia | Atrial Flutter | Atrial Fibrillation, Persistent | Atrial Tachycardia | Atrial Arrhythmia | Atrial Fibrillation Paroxysmal | Atrial Fibrillation, Paroxysmal or PersistentUnited States, Belgium, Netherlands, Czechia
-
AtriCure, Inc.Active, not recruitingPersistent Atrial Fibrillation | Atrial Fibrillation (AF) | Longstanding Persistent Atrial FibrillationUnited States
-
Barts & The London NHS TrustAtriCure, Inc.Not yet recruitingAtrial Fibrillation, Persistent | Persistent Atrial Fibrillation | Atrial Arrhythmia | Atrium; FibrillationUnited Kingdom
-
Maastricht University Medical CenterRWTH Aachen UniversityUnknownAtrial Fibrillation (Paroxysmal) | Atrial Fibrillation Recurrent | Atrial Fibrillation Common Gene VariantsNetherlands
-
Vivek ReddyEnrolling by invitationAtrial Fibrillation and Flutter | Atrial Flutter Typical | Atrial Fibrillation, Paroxysmal or PersistentUnited States
-
Fundació Institut de Recerca de l'Hospital de la...RecruitingAtrial Arrhythmia | Atrial Fibrillation and Flutter | Atrial Fibrillation RecurrentSpain
-
Adagio MedicalRecruitingAtrial Fibrillation | Atrial Flutter | Paroxysmal Atrial Fibrillation | Persistent Atrial FibrillationNetherlands, Germany, Belgium
-
St. George's Hospital, LondonRecruitingAtrial Fibrillation | Atrial Fibrillation, Persistent | Persistent Atrial Fibrillation | Atrial ArrhythmiaUnited Kingdom
-
R-PharmFSBI "National Medical Research Center of Cardiology named after academician...CompletedAtrial Flutter | Paroxysmal Atrial Fibrillation | Persistent Atrial FibrillationRussian Federation
Clinical Trials on Rate vs rhythm control strategies for atrial fibrillation
-
University of Turin, ItalyUniversity of Padova; Centro Cardiologico Monzino; Policlinico Casilino ASL RMB; Humanitas Research Hospital IRCCS, Rozzano-MilanUnknownPersistent Atrial Fibrillation | Congestive Heart Failure Due to Left Ventricular Systolic Dysfunction
-
Ziekenhuis Oost-LimburgRecruiting
-
Universitätsklinikum Hamburg-EppendorfUMC Utrecht; Hotchkiss Brain Institute, University of Calgary; Kompetenznetz... and other collaboratorsNot yet recruitingAtrial Fibrillation | Acute Ischemic Stroke
-
Electrophysiology Research FoundationRecruitingHeart Failure | Atrial Fibrillation | Diastolic Heart FailureUnited States, Germany, Switzerland
-
Mayo ClinicNational Heart, Lung, and Blood Institute (NHLBI); Abbott Medical Devices; Biosense...CompletedAtrial Fibrillation | ArrhythmiaChina, United States, Canada, Australia, Korea, Republic of, Germany, Czechia, Italy, Russian Federation, United Kingdom
-
Royal Brompton & Harefield NHS Foundation TrustCompletedHeart Failure | Atrial FibrillationUnited Kingdom
-
Abbott Medical DevicesCompletedHeart Failure | Persistent Atrial Fibrillation | ICDGermany, Hungary, Spain