Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT)

August 24, 2023 updated by: Anthony Tang, Ottawa Heart Institute Research Corporation
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Cardiovascular mortality is decreasing in most industrial countries, however mortality for congestive heart failure is increasing. The most important predictors of mortality in heart failure patients are depressed left ventricular function, severity of symptoms (NYHA class), and ventricular conduction abnormality manifested as wide QRS. Recent advances in pharmacological therapy including ACE inhibitors, beta-blocker and spironolactone have resulted in improvement of symptoms and reduction in mortality. Population epidemiological studies demonstrated that mortality and hospitalization rate for heart failure remains very high despite recent pharmacological therapeutic progress. Recent short-term clinical trials demonstrated that cardiac resynchronization therapy (CRT) is effective in improving symptoms of heart failure, functional capacity and quality of life in patients with moderate to severe heart failure and conduction abnormality optimally treated with drug therapy. However, the data for morbidity and mortality in mild to moderate heart failure is lacking.

The objective of this trial is to determine if the addition of CRT to optimal pharmacological therapy and ICD is effect in reducing mortality and morbidity in patients with poor LV function, wide QRS and mild to moderate heart failure symptoms.

This is a double-blinded randomized control trial. A total of 1800 patients with mild to moderate heart failure symptoms, LVEF ≤ 30%, and QRS ≥ 120 ms will be included in the study. Patients will be randomized to either "ICD plus Optimal Medical Therapy (control)" or "CRT/ICD plus Optimal Medical Therapy (experimental)" in a 1:1 randomization ratio. Patients in the control group will be implanted with a single or dual chamber ICD. Patients in the experimental group will receive a device with the capabilities of CRT and ICD. Optimal Medical Therapy will include ACE inhibitors and beta-blockers. Patients will be followed on a regular basis and will have clinical evaluation, quality of life assessment, and six minute walk tests performed. The primary outcome is a composite of total mortality and heart failure hospitalization. Secondary outcome measures will include total mortality, cardiovascular mortality, sudden arrhythmic death, health related quality of life and cost economics. Patient accruement is scheduled for 4.5 years and a minimum follow of 18 months.

DFT sub study:

Overview of sub-study Design Patients participating in the RAFT trial, at participating sites, will be randomized to have DFT testing or no testing at the time of device implant. Up to 450 patients will be eligible for enrollment at Canadian and European centres. The study will have two primary outcomes: a short-term safety outcome and a long-term efficacy outcome. The safety outcome will be a composite of all adverse events potentially related to DFT that occur within 30 days following ICD implant. The long-term efficacy outcome will be a composite of failed first appropriate clinical ICD shock and sudden death. This pilot study is intended primarily to confirm the anticipated rates of events and to demonstrate feasibility of enrollment, but will not have statistical power to determine if intra-operative DFT testing is associated with significant short-term risk. If complication rates are as high as predicted and enrollment is feasible, then a larger study would be justified to determine the impact of intra-operative DFT testing on long-term rates of failed appropriated ICD shocks and sudden death. Events rates determined in this pilot study would then be used to estimate the sample size of this larger study.

Sub-study Long-Term Outcomes of the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT)

Coordinating Investigator:

John L. Sapp, Jr., MD, FRCPC

Funder:

John Sapp, QEII Div. of Cardiology, Halifax, NS

Coordinating Center:

QEII Heart Rhythm Research, Halifax, NS

The Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT) was a multicenter, double-blind, randomized, controlled trial that aimed to determine whether the addition of CRT to an ICD, along with optimal medical therapy would reduce mortality and the rate of hospitalizations for HF, as compared to an ICD and optimal medical therapy alone. However, despite the established benefits of CRT among patients with mild to moderate HF, long term data is still lacking. We propose to determine the sustained, long-term outcomes of CRT among this high-risk patient population. A total of 8 sites enrolled more than 100 patients. Those 8 sites will ascertain long-term rates of survival, heart transplant and implantation of ventricular assist devices in a total of 1050 patients. The primary outcome will be all cause mortality. A secondary outcome will be the composite of mortality, implantation of ventricular assist device, and transplant. The 8 sites include UOHI, LHSC, QEII, Libin CV Calgary, HHSC, MHI, VCAT and Mazankowski Alberta Heart Institute.

The primary outcome is mortality (all cause). The primary analysis will compare the CRT-D and ICD groups for time to mortality. The survival experience (time-to-event) in each of the two groups will be analyzed using Kaplan-Meier product limit estimates and the nonparametric log-rank test. The hazard ratio (HR) and associated 95% CI will be calculated. In addition, the Cox proportional hazards model will be used to assess the consistency of the therapy group effect on this outcome taking the randomization stratification factors (clinical center, atrial rhythm (atrial fibrillation or flutter or sinus-atrial pacing), and a planned implantation of a single- or dual-chamber ICD)); as well, the Cox proportional hazards model analysis will be conducted as a sensitivity analysis to assess the therapy group effect on mortality while accounting for important baseline characteristics (any variable with a p value of less than 0.10 at baseline). Underlying assumptions for these statistical procedures will be assessed; in particular, the proportional hazard's assumption will be assessed using graphical (i.e., visual inspection of the log-negative-log plot) and numerical tests (i.e., test of the interaction term group x time). Should this assumption fail, a stratified Cox model will be fitted in order to correct for non-proportional hazards or, if ineffective, time-dependent variables will be introduced. In addition, chi-square tests will be used to compare the Kaplan-Meier (actuarial) rate of event-free survival at 10 years. The ITT population will be used.

The secondary outcome is the composite outcome of ventricular assist device implant (LVAD) or heart transplant or mortality (all cause). The primary analysis will compare the CRT-d and ICD groups for this composite outcome. For this analysis, the time-to-event analysis for Study Questions 1 will be followed. In addition, chi-square tests will be used to compare the Kaplan-Meier (actuarial) rate of event-free survival at 10 years. Also, the event rates for the composite outcome will be calculated for each therapy group and the relative risk (RR) and 95% CI calculated.

Secondary analysis - As a sensitivity analysis, the analysis for the primary and secondary questions 1 and will be repeated for the PP population.

Subgroup analysis - Subgroup analyses based on patient characteristics will be undertaken, primarily for sensitivity analyses to assess the robustness of the results, as well as for exploratory purposes for hypothesis generation. In particular, planned subgroups include: age (<65, ≥65), sex (male, female), NYHA Class (I, II), ischemic heart disease (<150, ≥150) paced QRS, LV ejection fraction, atrial rhythm (permanent Afib/flutter, sinus or atrial paced). The interaction of the therapy and subgroup will be included in the models.

Study Type

Interventional

Enrollment (Actual)

1798

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Adelaide, Australia, 5000
        • Royal Adelaide Hospital
      • Perth, Australia, 6009
        • Sir Charles Gairdner Hospital
  • Belgium
      • Leuven, Belgium
        • University Ziekenhuis
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
        • University of Calgary/Foothill Hospital
      • Edmonton, Alberta, Canada, T6G 2B7
        • Alberta Heart Institute
    • British Columbia
      • Vancouver, British Columbia, Canada, V6Z 1Y6
        • St. Paul's Hospital
      • Victoria, British Columbia, Canada, V8R 4R2
        • Victoria Cardiac Arrhythmia Trials
    • New Brunswick
      • St. John, New Brunswick, Canada, E2L 4L2
        • NB Heart Centre Research Initiative
    • Newfoundland and Labrador
      • St. Johns, Newfoundland and Labrador, Canada, A1B 3V6
        • Memorial Hospital
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 3A7
        • Queen Elizabeth II
    • Ontario
      • Hamilton, Ontario, Canada, L8L 2X2
        • Hamilton Health Sciences Centre
      • Kingston, Ontario, Canada, K7L 2V7
        • Kingston General Hospital
      • Kitchener, Ontario, Canada, N2M 1B2
        • St. Mary's Hospital
      • London, Ontario, Canada, N6A 5A5
        • London Health Sciences Centre
      • Newmarket, Ontario, Canada, L3Y 8C3
        • Southlake Regional Health Care
      • Ottawa, Ontario, Canada, K1Y 4 W7
        • University of Ottawa Heart Institute
      • Toronto, Ontario, Canada, M5B 1W8
        • St. Michael's Hospital
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Hospital
      • Toronto, Ontario, Canada, M5G 2M9
        • UHN Toronto General
    • Quebec
      • Montreal, Quebec, Canada, H1T 1C8
        • Montreal Heart Institute
      • Montreal, Quebec, Canada, H3A 1A1
        • McGill University Health Centre
      • Montreal, Quebec, Canada, H4J 1C5
        • Hopital Du Sacre Coeur de Montreal
      • Montreal, Quebec, Canada, H2L 4M1
        • CHUM Hopital Notre Dame
      • Quebec City, Quebec, Canada, G1V 4G5
        • Laval Hospital
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • CHUS Centre Hospitalier Universitaire de Sherbrooke
  • Denmark
      • Aarhus, Denmark
        • Skejby University Hospital
  • Germany
      • Bad Berka, Germany
        • Zentralklinik
      • Frankfurt, Germany, 60590
        • J.W. Goethe University
      • Giessen, Germany
        • University of Giessen
      • Ludwigshafen, Germany
        • Ludwigshafen
      • Mainz, Germany
        • University of Mainz
  • Netherlands
      • Zwolle, Netherlands
        • Isala Klinieken
  • Turkey
      • Izmir, Turkey
        • Ege University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • Patients with an existing ICD (patients with an existing pacemaker may be included if the patients satisfy all other inclusion/exclusion criteria)
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1. Optimal Medical therapy plus ICD
Device: Optimal Medical Therapy plus ICD
ICD vs CRT/ICD
Active Comparator: 2. Optimal Medical Therapy plus CRT/ICD
Device: Optimal Medical Therapy plus CRT/ICD
ICD vs CRT/ICD

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Primary outcome is a composite of all cause total mortality and hospitalization for CHF
Time Frame: Study end
Study end

Secondary Outcome Measures

Outcome Measure
Time Frame
Total mortality
Time Frame: Study end
Study end
Cardiovascular mortality
Time Frame: Study end
Study end
Sudden arrhythmic death
Time Frame: Study end
Study end
Progressive HF death
Time Frame: Study end
Study end
All cause hospitalization rate
Time Frame: Study end
Study end
CHF hospitalization rate
Time Frame: Study end
Study end
Health related quality of life
Time Frame: Study end
Study end
Cost economics
Time Frame: Study end
Study end

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ottawa Heart Institute Research Corporation

Collaborators

Canadian Institutes of Health Research (CIHR)
Medtronic

Investigators

  • Principal Investigator: George Wells, PhD, Ottawa Heart Institute Research Corporation
  • Principal Investigator: Anthony Tang, MD, Ottawa Heart Institute Research Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2003

Primary Completion (Actual)

September 1, 2010

Study Completion (Actual)

May 1, 2011

Study Registration Dates

First Submitted

November 8, 2005

First Submitted That Met QC Criteria

November 8, 2005

First Posted (Estimated)

November 9, 2005

Study Record Updates

Last Update Posted (Actual)

August 28, 2023

Last Update Submitted That Met QC Criteria

August 24, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FRN 63208

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.

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