Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00251251 |
| Other study ID # |
FRN 63208 |
| Secondary ID |
FRN 63208 |
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
April 2003 |
| Est. completion date |
May 2011 |
Study information
| Verified date |
August 2023 |
| Source |
Ottawa Heart Institute Research Corporation |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
