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

NCT ID: NCT01994252

Last Updated: 2024-05-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2024-09-30

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.

Conditions

Heart Disease; Congestive Heart Failure; Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Optimal Medical therapy plus ICD

Patients randomized to the (ICD) Implantable-Defibrillator-Cardioverter only group will receive an ICD + optimal medical therapy

Group Type: ACTIVE_COMPARATOR

Optimal Medical therapy plus ICD

Intervention Type: DEVICE

Optimal Medical therapy plus CRT/ICD

Patients randomized to the (ICD) Implantable-Defibrillator-Cardioverter plus cardiac resynchronisation therapy (CRT) group will receive an ICD + CRT and optimal medical therapy

Group Type: ACTIVE_COMPARATOR

Optimal Medical therapy plus CRT/ICD

Intervention Type: DEVICE

Interventions

Optimal Medical therapy plus ICD

Intervention Type: DEVICE

Optimal Medical therapy plus CRT/ICD

Intervention Type: DEVICE

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Ottawa Heart Institute Research Corporation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anthony SL Tang, MD

Role: PRINCIPAL_INVESTIGATOR

Ottawa Heart Institute Research Corporation

Locations

Libin Cardiovascular Institute of Alberta

Calgary, Alberta, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

Victoria Cardiac Arrhythmia Trials

Victoria, British Columbia, Canada

St. Boniface General Hospital

Winnipeg, Manitoba, 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

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

St. Michael's General Hospital

Toronto, Ontario, Canada

CHUM Centre hospitalier universitaire de Montréal

Montreal, Quebec, Canada

McGill Health Science Centre

Montreal, Quebec, Canada

Montreal Heart Institute

Montreal, Quebec, Canada

Institut universitaire de cardiologie et de pneumologie de Quebec

Québec, Quebec, Canada

Le Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Countries

Canada

References

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.

Reference Type: BACKGROUND

PMID: 21073365 (View on PubMed)

Other Identifiers

RN00208414

Identifier Type: -

Identifier Source: org_study_id