Ignite Creation Date:
2024-05-05 @ 12:08 PM
Last Modification Date:
2024-10-26 @ 9:20 AM
Study NCT ID:
NCT00251251
Status:
COMPLETED
Last Update Posted:
2023-08-28
First Post:
2005-11-08
Brief Title:
ResynchronizationDefibrillation for Ambulatory Heart Failure Trial
Sponsor:
Ottawa Heart Institute Research Corporation
Organization:
Ottawa Heart Institute Research Corporation
Study Overview
Official Title:
ResynchronizationDefibrillation for Ambulatory Heart Failure Trial
Status:
COMPLETED
Status Verified Date:
2023-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RAFT
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
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 CRTICD plus Optimal Medical Therapy experimental in a 11 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 45 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 010 at baseline Underlying assumptions for these statistical procedures will be assessed in particular the proportional hazards assumption will be assessed using graphical ie visual inspection of the log-negative-log plot and numerical tests ie 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 Afibflutter sinus or atrial paced The interaction of the therapy and subgroup will be included in the models
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 CRTICD plus Optimal Medical Therapy experimental in a 11 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 45 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 010 at baseline Underlying assumptions for these statistical procedures will be assessed in particular the proportional hazards assumption will be assessed using graphical ie visual inspection of the log-negative-log plot and numerical tests ie 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 Afibflutter sinus or atrial paced The interaction of the therapy and subgroup will be included in the models
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| FRN 63208 | None | None | None |