Clinical trial NCT01994252: Resynchronization/Defibrillation for Ambulatory Heart Failure Trial in Patients With Permanent Atrial Fibrillation
Official title: Resynchronization/Defibrillation for Ambulatory Heart Failure Trial in Patients With Permanent Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Heart Disease
Congestive Heart Failure
Atrial Fibrillation
Keywords: defibrillator
cardiac resynchronization
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2013-11-25
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Atrial fibrillation (AF) and heart failure (HF) are two common heart conditions that are encountered with an increase in death and suffering. When both these two conditions occur in a patient, the patient's prognosis is poor with a reduced quality of life and impaired heart function. These patients have enlarged hearts, specifically the left ventricle (major pumping chamber), which impairs the heart's pumping capacity, leading to symptoms such as fatigue, shortness of breath from any type of exertion, and swelling, usually of the feet and ankles.

In these HF patients who are in AF all of the time, who would otherwise be a suitable candidate for an implantable defibrillator to prevent sudden cardiac death, we would like to determine whether adding pacing of both ventricles will reduce heart size (left ventricular end systolic volume index LVESVi) as measured by ultrasound, which can improve its function and help the heart pump more efficiently.

Other studies have shown that adding pacing to both ventricles is of benefit in HF patients with mild to moderate symptoms and have a regular heart rhythm. The Investigators now want to explore if this therapy will benefit those patients with a permanent irregular heart rhythm (AF).

Detailed description: Heart failure (HF) is increasing in prevalence and incidence and is the most common reason for hospital admissions of patients over the age of 65. Therapy for HF has evolved over the last two decades. Cardiac resynchronization therapy (CRT) is a therapy that attempts to resynchronize the sequence of ventricular contraction in heart failure (HF) patients with left ventricular (LV) systolic dysfunction and ventricular dyssynchrony. CRT is achieved by stimulating both RV and LV together, synchronized to right atrial excitation to achieve atrio-ventricular synchrony. Clinical trials have demonstrated that CRT reduced heart size, improved survival and reduced HF hospitalization in mild to advanced HF patients. This knowledge translated to a change in practice guidelines and the adoption of CRT into clinical practice benefitting many HF patients CRT is now an important state-of-the-art therapy for HF patients with LV systolic dysfunction, low LVEF, and prolonged QRS duration in sinus rhythm, since the vast majority of the CRT clinical research was performed in patients in sinus rhythm. However, in the \~25% of HF patients with permanent atrial fibrillation (AF), the effectiveness of CRT is not clear. It is therefore timely to address the question of whether the addition of CRT to optimal HF treatment, rate control and an ICD improves cardiac outcomes in individuals with heart failure (HF) and permanent atrial fibrillation (AF). The outcomes will be measured by a hierarchy of all-cause mortality, HF events, Left Ventricular Ejection Fraction (LVEF) and improvement in Quality of Life (QoL) in patients with permanent AF, mild to moderate HF, left ventricular (LV) systolic dysfunction, and prolonged QRS duration, when compared to implantable cardioverter defibrillator (ICD) therapy alone.

Objectives: To determine whether cardiac resynchronization therapy will improve cardiac outcomes for heart failure patients with permanent atrial fibrillation, mild to moderate heart failure, left ventricular systolic dysfunction, and prolonged QRS duration, when compared to implantable cardioverter defibrillator (ICD) therapy alone.

Methods: This is a multi-centre randomized controlled trial of two treatment groups. The patients, primary physicians and the heart failure caregivers will be blinded to the treatment allocation. The device follow-up caregivers will not be blinded. Patients with NYHA Class II and III HF symptoms, LVEF HF ≤ 35%, permanent AF, on optimal medical therapy and QRS durations ≥ 130 ms when the QRS morphology is LBBB, or QRS durations ≥ 150 ms when the QRS morphology is non-LBBB, or Paced QRS will be included in the trial. Patients should be suitable candidates for either of the 2 treatment strategies. There will be 200 patients randomized in 1:1 ratio to two groups: 1) ICD-CRT, 2) ICD only. All patients will undergo baseline clinical evaluation, echocardiogram measurements, quality of life assessment, medication assessment, and 6-minute walk distance.. The patients will be followed at 1 month, 3 months, 6 months and then every 6 months.

Eligibility criteria: Inclusion Criteria:

* Patients with NYHA Class II or III HF symptoms (assessment in the last 3 months)
* Permanent AF
* Optimal Medical Therapy for HF of at least 3 months (according to 2009 ACCF/AHA and ESC 2012 recommendations,)
* LVEF ≤ 35% (assessment in the last 6 months)
* Candidacy for an ICD for primary or secondary prevention of sudden cardiac death
* QRS durations ≥ 130 ms when the QRS morphology is LBBB, or QRS durations ≥ 150 ms when the QRS morphology is non-LBBB or Paced QRS

Exclusion Criteria:

* In-hospital patients who have acute cardiac or non-cardiac illness that requires intensive care
* Intra-venous inotropic agent in the last 4 days
* Patients with a life expectancy of less than one year from non-cardiac cause.
* Expected to undergo cardiac transplantation within one year (status I)
* Acute coronary syndrome (including MI) \< 4 weeks
* Unable or unwilling to provide informed consent
* Uncorrected or uncorrectable primary valvular disease
* Restrictive, hypertrophic or reversible form of cardiomyopathy
* Severe primary pulmonary disease such as cor pulmonale
* Tricuspid prosthetic valve
* Patients included in other clinical trial that will affect the objectives of this study
* Coronary revascularization (CABG or PCI) \< 3 months
* Patients with an existing ICD or CRT pacemaker

Primary outcomes:
measure: The primary outcome is a hierarchy (winratio) of 1) all-cause mortality
timeFrame: 12 months
measure: The primary outcome is a hierarchy (winratio) of 2) Heart Failure Events (>24 Hours admission for Heart Failure or clinically worsening Heart Failure leading to IV diuretics administered
timeFrame: 12 months
measure: The primary outcome is a hierarchy (winratio) of 3) Left ventricular ejection fraction
timeFrame: baseline to 12 months
measure: The primary outcome is a hierarchy (winratio) of 4) QoL - Minnesota Living with Heart Failure Questionnaire
timeFrame: baseline to 12 months
Secondary outcomes:
measure: All-cause mortality
timeFrame: Baseline to a minimum of 12 months
measure: Heart Failure Events
timeFrame: Baseline to a minimum of 12 months
measure: Changes in LVEF
timeFrame: Baseline to 12 months
measure: Quality of Life Questionnaire
timeFrame: Baseline to a minimum of 12 months
measure: Composite of all-cause mortality and heart failure
timeFrame: Baseline to a minimum of 12 months
measure: 6 Minute walk distance
timeFrame: Baseline to a minimum of 12 months
measure: Cardiovascular mortality
timeFrame: Baseline to a minimum of 12 months
measure: Cost-effectiveness
timeFrame: Baseline to a minimum of 12 months
measure: Cardiovascular hospitalizations
timeFrame: Baseline to a minimum of 12 months
measure: Quality of Life Questionnaire
timeFrame: Baseline to a minimum of 12 months
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Libin Cardiovascular Institute of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Victoria
country: Canada
facility: Victoria Cardiac Arrhythmia Trials
state: British Columbia
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
state: Manitoba
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Science
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's General Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill Health Science Centre
state: Quebec
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montréal
country: Canada
facility: CHUM Centre hospitalier universitaire de Montréal
state: Quebec
city: Quebec City
country: Canada
facility: Institut universitaire de cardiologie et de pneumologie de Quebec
state: Quebec
city: Sherbrooke
country: Canada
facility: Le Centre hospitalier universitaire de Sherbrooke
state: Quebec
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: Anthony SL Tang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tang AS, Wells GA, Talajic M, Arnold MO, Sheldon R, Connolly S, Hohnloser SH, Nichol G, Birnie DH, Sapp JL, Yee R, Healey JS, Rouleau JL; Resynchronization-Defibrillation for Ambulatory Heart Failure Trial Investigators. Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med. 2010 Dec 16;363(25):2385-95. doi: 10.1056/NEJMoa1009540. Epub 2010 Nov 14.