Resynchronization/Defibrillation for Ambulatory Heart Failure Trial in Patients With Permanent Atrial Fibrillation

Atrial Fibrillation Clinical Trial

— RAFT-PermAF  

Official title:

Resynchronization/Defibrillation for Ambulatory Heart Failure Trial in Patients With Permanent Atrial Fibrillation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01994252
• Other study ID #: RN00208414
• Status: Active, not recruiting
• Phase: N/A
• Start date: August 2013
• Est. completion date: September 2024

Study information

• Verified date: May 2024
• Source: Ottawa Heart Institute Research Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Congestive Heart Failure
• Heart Disease
• Heart Diseases
• Heart Failure

Intervention

Device:
• Optimal Medical therapy plus ICD

• Optimal Medical therapy plus CRT/ICD

Locations

Country	Name	City	State
Canada	Libin Cardiovascular Institute of Alberta	Calgary	Alberta
Canada	Queen Elizabeth II Health Science	Halifax	Nova Scotia
Canada	Hamilton Health Sciences	Hamilton	Ontario
Canada	Kingston General Hospital	Kingston	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	McGill Health Science Centre	Montreal	Quebec
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	CHUM Centre hospitalier universitaire de Montréal	Montréal	Quebec
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	Institut universitaire de cardiologie et de pneumologie de Quebec	Quebec City	Quebec
Canada	Le Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	St. Michael's General Hospital	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	Victoria Cardiac Arrhythmia Trials	Victoria	British Columbia
Canada	St. Boniface General Hospital	Winnipeg	Manitoba

Sponsors (2)

Lead Sponsor	Collaborator
Ottawa Heart Institute Research Corporation	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome is a hierarchy (winratio) of 1) all-cause mortality	Mortality data will be collected for the duration of the study	12 months
Primary	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	HF events (> 24 hour admit or < 24 hr with IV diuretics) will be collected for the duration of the study	12 months
Primary	The primary outcome is a hierarchy (winratio) of 3) Left ventricular ejection fraction	Change in echocardiogram parameters LVEF measure	baseline to 12 months
Primary	The primary outcome is a hierarchy (winratio) of 4) QoL - Minnesota Living with Heart Failure Questionnaire	Change in QoL MLHFQ. The MLHFQ score is used to measure quality of life. The MLHFQ consists of 21 questions answered on a 0-5 likert scale, with higher scores indicating a stronger impact of heart failure on QoL.	baseline to 12 months
Secondary	All-cause mortality	Death all cause	Baseline to a minimum of 12 months
Secondary	Heart Failure Events	Admission to Hospital > 24 hrs for Heart Failure or <24 hrs with clinical worsending of HF leading to intervention	Baseline to a minimum of 12 months
Secondary	Changes in LVEF	Left Ventricular ejection fraction	Baseline to 12 months
Secondary	Quality of Life Questionnaire	Minnesota Living with Heart Failure	Baseline to a minimum of 12 months
Secondary	Composite of all-cause mortality and heart failure	All cause death and admission to to Hospital > 24 hours for Heart Failure	Baseline to a minimum of 12 months
Secondary	6 Minute walk distance	Hall walk distance over 6 minute timeframe	Baseline to a minimum of 12 months
Secondary	Cardiovascular mortality	Cardiovascular Death	Baseline to a minimum of 12 months
Secondary	Cost-effectiveness	Readmission for Heart Failure	Baseline to a minimum of 12 months
Secondary	Cardiovascular hospitalizations	Cardiovascular Admission to Hospital > 24 hours	Baseline to a minimum of 12 months
Secondary	Quality of Life Questionnaire	EQ5D-5L	Baseline to a minimum of 12 months