Resynchronization/Defibrillation for Ambulatory Heart Failure Trial

NCT00251251 | Completed DMC

• 1 other identifier: FRN 63208
• Study Type: interventional
• Target: 1,798
• Locations: 7 countries
• Sites: 33

Brief Summary

Congestive heart failure (CHF) is a common health problem that leads to frequent hospitalizations and an increased death rate. In spite of advances in drug therapy, it remains a significant public health problem. Recently, a new therapy has been developed for advanced heart failure patients with a ventricular conduction abnormality. This new therapy, called cardiac resynchronization (CRT), is a device which stimulates the atrium, the right ventricle, and the left ventricle providing synchronization of the contraction of the heart chambers. It is the addition of this therapy to an implantable cardioverter defibrillator (ICD) that will be evaluated in this study. This study will compare whether the implantation of this new therapy device, in combination with an implantable cardioverter defibrillator, will reduce total mortality and hospitalizations for CHF.

Conditions

Heart Failure, Congestive

Keywords

Congestive heart failure; Multicentre randomized controlled trial; Defibrillator; Cardiac resynchronization; Sudden death/mortality; Hospitalization; ICD indication; NYHA Class II; LVEF </equal to 30%; QRS >/equal to 120 ms

Outcome Measures

Primary Outcomes (1)

• Primary outcome is a composite of all cause total mortality and hospitalization for CHF

  Study end

Secondary Outcomes (8)

• Total mortality

  Study end

• Cardiovascular mortality

  Study end

• Sudden arrhythmic death

  Study end

• Progressive HF death

  Study end

• All cause hospitalization rate

  Study end

Study Arms (2)

1. Optimal Medical therapy plus ICD

ACTIVE COMPARATOR

Device: Optimal Medical Therapy plus ICD

2. Optimal Medical Therapy plus CRT/ICD

ACTIVE COMPARATOR

Device: Optimal Medical Therapy plus CRT/ICD

Interventions

Optimal Medical Therapy plus ICD DEVICE

ICD vs CRT/ICD

1. Optimal Medical therapy plus ICD

Optimal Medical Therapy plus CRT/ICD DEVICE

ICD vs CRT/ICD

2. Optimal Medical Therapy plus CRT/ICD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• New York Heart Association (NYHA) Class II
• Left ventricular ejection fraction (LVEF) less than or equal to 30% by multigated acquisition scan (MUGA)/catheterization OR LVEF less than or equal to 30% and LV end diastolic dimension ≥ 60 mm (by echocardiogram) within 6 months prior to randomization
• Intrinsic QRS complex width ≥ 120 ms OR paced QRS measurement ≥ 200 ms
• ICD indication for primary or secondary prevention
• Optimal heart failure pharmacological therapy
• Normal sinus rhythm; OR chronic persistent atrial tachyarrhythmia with resting ventricular heart rate ≤ 60 beats per minute (bpm) and 6 minute hall walk ventricular heart rate of ≤ 90 bpm; OR chronic persistent atrial tachyarrhythmia with resting ventricular heart rate \> 60 bpm and 6 minute hall walk ventricular heart rate of \> 90 bpm and booked for atrioventricular junction ablation.

You may not qualify if:

• Intravenous 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)
• In hospital patients who have acute cardiac or non-cardiac illness that requires intensive care
• Uncorrected or uncorrectable primary valvular disease
• Restrictive, hypertrophic, or reversible form of cardiomyopathy
• Severe primary pulmonary disease such as cor pulmonale
• Tricuspid prosthetic valve
• Coronary revascularization (coronary artery bypass graft surgery \[CABG\] or percutaneous coronary intervention \[PCI\]) \< 1 month if previously determined LVEF \> 30%. Patients with a more recent revascularization can be included if a previously determined LVEF was ≤ 30%.
• Patients with an acute coronary syndrome including myocardial infarction (MI) can be included if the patients have had a previous MI with LV dysfunction (LVEF ≤ 30%).
• Patients included in another clinical trial that will affect the objectives of this study
• History of noncompliance to medical therapy
• Unable or unwilling to provide informed consent

Sponsors & Collaborators

• Ottawa Heart Institute Research Corporation: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Medtronic: collaborator

Study Sites (33)

Royal Adelaide Hospital

Adelaide, 5000, Australia

Location

Sir Charles Gairdner Hospital

Perth, 6009, Australia

Location

University Ziekenhuis

Leuven, Belgium

Location

University of Calgary/Foothill Hospital

Calgary, Alberta, T2N 2T9, Canada

Location

Alberta Heart Institute

Edmonton, Alberta, T6G 2B7, Canada

Location

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Victoria Cardiac Arrhythmia Trials

Victoria, British Columbia, V8R 4R2, Canada

Location

NB Heart Centre Research Initiative

Saint John, New Brunswick, E2L 4L2, Canada

Location

Memorial Hospital

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

Queen Elizabeth II

Halifax, Nova Scotia, B3H 3A7, Canada

Location

Hamilton Health Sciences Centre

Hamilton, Ontario, L8L 2X2, Canada

Location

Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

St. Mary's Hospital

Kitchener, Ontario, N2M 1B2, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

Location

Southlake Regional Health Care

Newmarket, Ontario, L3Y 8C3, Canada

Location

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4 W7, Canada

Location

Sunnybrook Hospital

Toronto, Ontario, M4N 3M5, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

UHN Toronto General

Toronto, Ontario, M5G 2M9, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

CHUM Hopital Notre Dame

Montreal, Quebec, H2L 4M1, Canada

Location

McGill University Health Centre

Montreal, Quebec, H3A 1A1, Canada

Location

Hopital du Sacre Coeur de Montreal

Montreal, Quebec, H4J 1C5, Canada

Location

Laval Hospital

Québec, Quebec, G1V 4G5, Canada

Location

CHUS Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Skejby University Hospital

Aarhus, Denmark

Location

Zentralklinik

Bad Berka, Germany

Location

J.W. Goethe University

Frankfurt, 60590, Germany

Location

University of Giessen

Giessen, Germany

Location

Ludwigshafen

Ludwigshafen, Germany

Location

University of Mainz

Mainz, Germany

Location

Isala Klinieken

Zwolle, Netherlands

Location

Ege University

Izmir, Turkey (Türkiye)

Location

Related Publications (14)

• Sapp JL, Sivakumaran S, Redpath CJ, Khan H, Parkash R, Exner DV, Healey JS, Thibault B, Sterns LD, Lam NHN, Manlucu J, Mokhtar A, Sumner G, McKinlay S, Kimber S, Mondesert B, Talajic M, Rouleau J, McCarron CE, Wells G, Tang ASL; RAFT Long-Term Study Team. Long-Term Outcomes of Resynchronization-Defibrillation for Heart Failure. N Engl J Med. 2024 Jan 18;390(3):212-220. doi: 10.1056/NEJMoa2304542.

  PMID: 38231622 DERIVED

• Fudim M, Dalgaard F, Friedman DJ, Abraham WT, Cleland JGF, Curtis AB, Gold MR, Kutyifa V, Linde C, Ali-Ahmed F, Tang A, Olivas-Martinez A, Inoue LYT, Al-Khatib SM, Sanders GD. Comorbidities and clinical response to cardiac resynchronization therapy: Patient-level meta-analysis from eight clinical trials. Eur J Heart Fail. 2024 Apr;26(4):1039-1046. doi: 10.1002/ejhf.3029. Epub 2023 Sep 15.

  PMID: 37671601 DERIVED

• Friedman DJ, Al-Khatib SM, Dalgaard F, Fudim M, Abraham WT, Cleland JGF, Curtis AB, Gold MR, Kutyifa V, Linde C, Tang AS, Ali-Ahmed F, Olivas-Martinez A, Inoue LYT, Sanders GD. Cardiac Resynchronization Therapy Improves Outcomes in Patients With Intraventricular Conduction Delay But Not Right Bundle Branch Block: A Patient-Level Meta-Analysis of Randomized Controlled Trials. Circulation. 2023 Mar 7;147(10):812-823. doi: 10.1161/CIRCULATIONAHA.122.062124. Epub 2023 Jan 26.

  PMID: 36700426 DERIVED

• Manlucu J, Sharma V, Koehler J, Warman EN, Wells GA, Gula LJ, Yee R, Tang AS. Incremental Value of Implantable Cardiac Device Diagnostic Variables Over Clinical Parameters to Predict Mortality in Patients With Mild to Moderate Heart Failure. J Am Heart Assoc. 2019 Jul 16;8(14):e010998. doi: 10.1161/JAHA.118.010998. Epub 2019 Jul 11.

  PMID: 31291801 DERIVED

• Bennett MT, Leader N, Sapp J, Parkash R, Gardner M, Healey JS, Thibault B, Sterns L, Essebag V, Birnie D, Sivakumaran S, Nery P, Andrade JG, Krahn AD, Tang A. Differentiating Ventricular From Supraventricular Arrhythmias Using the Postpacing Interval After Failed Antitachycardia Pacing. Circ Arrhythm Electrophysiol. 2018 Apr;11(4):e005921. doi: 10.1161/CIRCEP.117.005921.

  PMID: 29618476 DERIVED

• Linde C, Cleland JGF, Gold MR, Claude Daubert J, Tang ASL, Young JB, Sherfesee L, Abraham WT. The interaction of sex, height, and QRS duration on the effects of cardiac resynchronization therapy on morbidity and mortality: an individual-patient data meta-analysis. Eur J Heart Fail. 2018 Apr;20(4):780-791. doi: 10.1002/ejhf.1133. Epub 2018 Jan 4.

  PMID: 29314424 DERIVED

• Sapp JL, Parkash R, Wells GA, Yetisir E, Gardner MJ, Healey JS, Thibault B, Sterns LD, Birnie D, Nery PB, Sivakumaran S, Essebag V, Dorian P, Tang AS. Cardiac Resynchronization Therapy Reduces Ventricular Arrhythmias in Primary but Not Secondary Prophylactic Implantable Cardioverter Defibrillator Patients: Insight From the Resynchronization in Ambulatory Heart Failure Trial. Circ Arrhythm Electrophysiol. 2017 Mar;10(3):e004875. doi: 10.1161/CIRCEP.116.004875.

  PMID: 28292754 DERIVED

• Wilton SB, Exner DV, Wyse DG, Yetisir E, Wells G, Tang AS, Healey JS. Frequency and Outcomes of Postrandomization Atrial Tachyarrhythmias in the Resynchronization/Defibrillation in Ambulatory Heart Failure Trial. Circ Arrhythm Electrophysiol. 2016 May;9(5):e003807. doi: 10.1161/CIRCEP.115.003807.

  PMID: 27162033 DERIVED

• Gillis AM, Kerr CR, Philippon F, Newton G, Talajic M, Froeschl M, Froeschl S, Swiggum E, Yetisir E, Wells GA, Tang AS. Impact of cardiac resynchronization therapy on hospitalizations in the Resynchronization-Defibrillation for Ambulatory Heart Failure trial. Circulation. 2014 May 20;129(20):2021-30. doi: 10.1161/CIRCULATIONAHA.112.000417. Epub 2014 Mar 7.

  PMID: 24610807 DERIVED

• Birnie DH, Ha A, Higginson L, Sidhu K, Green M, Philippon F, Thibault B, Wells G, Tang A. Impact of QRS morphology and duration on outcomes after cardiac resynchronization therapy: Results from the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT). Circ Heart Fail. 2013 Nov;6(6):1190-8. doi: 10.1161/CIRCHEARTFAILURE.113.000380. Epub 2013 Aug 30.

  PMID: 23995437 DERIVED

• Cleland JG, Abraham WT, Linde C, Gold MR, Young JB, Claude Daubert J, Sherfesee L, Wells GA, Tang AS. An individual patient meta-analysis of five randomized trials assessing the effects of cardiac resynchronization therapy on morbidity and mortality in patients with symptomatic heart failure. Eur Heart J. 2013 Dec;34(46):3547-56. doi: 10.1093/eurheartj/eht290. Epub 2013 Jul 29.

  PMID: 23900696 DERIVED

• Healey JS, Hohnloser SH, Exner DV, Birnie DH, Parkash R, Connolly SJ, Krahn AD, Simpson CS, Thibault B, Basta M, Philippon F, Dorian P, Nair GM, Sivakumaran S, Yetisir E, Wells GA, Tang AS; RAFT Investigators. Cardiac resynchronization therapy in patients with permanent atrial fibrillation: results from the Resynchronization for Ambulatory Heart Failure Trial (RAFT). Circ Heart Fail. 2012 Sep 1;5(5):566-70. doi: 10.1161/CIRCHEARTFAILURE.112.968867. Epub 2012 Aug 14.

  PMID: 22896584 DERIVED

• Healey JS, Gula LJ, Birnie DH, Sterns L, Connolly SJ, Sapp J, Crystal E, Simpson C, Exner DV, Kus T, Philippon F, Wells G, Tang AS. A randomized-controlled pilot study comparing ICD implantation with and without intraoperative defibrillation testing in patients with heart failure and severe left ventricular dysfunction: a substudy of the RAFT trial. J Cardiovasc Electrophysiol. 2012 Dec;23(12):1313-6. doi: 10.1111/j.1540-8167.2012.02393.x. Epub 2012 Jul 12.

  PMID: 22788915 DERIVED

• 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.

  PMID: 21073365 DERIVED

MeSH Terms

Conditions

Heart Failure; Death, Sudden

Interventions

Defibrillators, Implantable

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Defibrillators; Electrodes; Electrical Equipment and Supplies; Equipment and Supplies; Electrodes, Implanted; Prostheses and Implants

Study Officials

• Anthony Tang, MD

  Ottawa Heart Institute Research Corporation

  PRINCIPAL INVESTIGATOR

• George Wells, PhD

  Ottawa Heart Institute Research Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 8, 2005
• First Posted: November 9, 2005
• Study Start: April 1, 2003
• Primary Completion: September 1, 2010
• Study Completion: May 1, 2011
• Last Updated: August 28, 2023

Record last verified: 2023-08

Locations

BE (1); DE (5); NL (1); TU (1); CA (22); AU (2); DK (1)