Heart Failure
Conditions
Keywords
Implantable cardioverter defibrillator, Intracardiac pressures
Brief summary
The purpose of this clinical research study is to evaluate the safety and effectiveness of the investigational implantable hemodynamic monitor (IHM), and of the IHM in combination with an implantable cardioverter defibrillator (ICD). The investigational IHM has the ability to record and report the force with which the heart pumps blood (heart pressures). When combined with the ICD, the device has the additional ability to send a strong electrical impulse, or shock, to the heart when it detects dangerously fast heartbeats to return it to a normal rhythm. The IHM and IHM/ICD are implanted surgically just under the skin in the upper chest area. This study will also determine how doctors use the information related to heart pressures in the management of heart failure.
Interventions
DEVICEImplantable Hemodynamic Monitor (Chronicle® IHM), and IHM in combination with single chamber ICD (Chronicle ICD)
Surgical implantation of hemodynamic device (IHM), or IHM/ICD, and intracardiac leads.
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with heart failure that only sometimes interferes with daily activities (New York Heart Association \[NYHA\] Class II (1)) or subjects with heart failure which severely limits daily activities (NYHA Class III (2)) at baseline * Subject has appropriate medical therapy for heart failure (such as diuretic, angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) and beta blocker) for at least three months prior to the baseline evaluation. * Subject has been on stable medications maximized to the subject's tolerance of ACE or ARB and beta blockers as determined by the study investigator for at least 30 days prior to baseline evaluation. (Stable is defined as no more than a 100% increase or a 50% decrease in dose.) If a subject is intolerant of ACE, ARB or beta blockers documented evidence must be available. * Subject has had at least one heart failure-related hospitalization or at least one heart failure-related emergency department or urgent care visit necessitating heart failure-related intravenous therapy (e.g. diuretic administration) within 12 months prior to the baseline evaluation * To be considered for Chronicle ICD: Subject has, or is at risk of having, a heart beat that is too fast and his/her doctor has determined he/she needs an implantable cardioverter defibrillator (ICD). 1. Class II Subjects with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or angina. 2. Class III Subjects with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or angina.
Exclusion criteria
* Subjects with severe heart failure who should always be resting (NYHA Class IV(3)) or Stage D(4) refractory heart failure. * Subjects with severe renal dysfunction. * Subjects with severe non-cardiac condition limiting 12-month survival. * Subjects in concurrent studies that may confound the results. (3)Class IV Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased. (4)Stage D refractory heart failure: Patients who have marked symptoms at rest despite maximal medical therapy (e.g., those who are recurrently hospitalized or cannot be safely discharged from the hospital without specialized interventions)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects With an Attempted Implant of the Chronicle ICD System Free From System-related Chronicle ICD Complications at 6-months Post-implant. | Within 6 months post-implant | A Chronicle ICD system-related complication was defined as any system-related adverse event that occurred during the clinical investigation which is (1) treated with invasive means (including intravenous drug therapy), (2) results in death or serious injury of subject, (3) results in the explant of any Chronicle ICD component,and/or (4) causes permanent loss of significant function of the implanted system. |
| Percent of Subjects With an Attempted Chronicle IHM Implant Free From Chronicle IHM System-related Complications at 6-months Post-implant | 6 months post implant | A Chronicle IHM system-related complication was defined as any system-related adverse event that occurred during the clinical investigation which is (1) treated with invasive means (including intravenous drug therapy), (2) results in death or serious injury of subject, (3) results in the explant of any Chronicle IHM component,and/or (4) causes permanent loss of significant function of the implanted system. |
| Relative Risk Reduction of All Heart Failure Related Events in the Treatment Group Compared to the Control Group | 12 months post-implant | The rate of HF-related events (hospitalizations \>24h, hospitalizations \<24h with IV therapy, ED visits with IV therapy, and urgent clinic visits with IV therapy) during the 12-month randomized follow-up period was compared between the Chronicle and Control groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative Risk of All-cause Events | 12 months post-implant | All-cause events were defined as hospitalizations, hospitalizations \<24 hours necessitating intravenous therapy, emergency department visits necessitating intravenous therapy or urgent visits necessitating intravenous therapy. |
| Percentage of Randomized Subjects at Each Level of the Composite Response Endpoint Between the Treatment Arm and the Control Arm. | 12 months post implant | The definitions of worsened, improved, and unchanged are as follows: Worsened: Subject dies, is hospitalized for worsening heart failure, permanently discontinues blinded randomized assignment and has worsening heart failure at time of study discontinuation, demonstrates worsening NYHA Class at LOCF, or moderate-marked worsening of global assessment score at LOCF. Improved: Subject has not worsened, and demonstrates improvement in NYHA class and/or moderate-marked improvement in subject global assessment score. Unchanged: Subject is neither worsened nor improved. |
| Characterize Health Resource Utilization | 12 months post implant | Percentage of randomized days spent in the intensive care unit for heart failure. Reason for hospitalization was determined by the adverse event adjudication committee. |
| Characterize Randomized Days Alive Out of Hospital | 12 months post implant | Randomized days alive outside of the hospital was computed for each subject as the total number of randomized days minus the number of randomized days spent in the hospital for any cause. |
| Characterize Subject Survival | 12 months post implant | Death from any cause during the 12-month randomization period |
| Characterize Medication Usage | 12 months post implant | The rate of change of cardiovascular medications in changes per subject month were computed and compared between treatment groups. |
| Characterize Intracardiac Pressure | 12 months post implant | The average daily median estimated pulmonary arterial diastolic pressure (ePAD) was computed for each subject with at least 90 days of ePAD data available and compared between the Treatment and Control arms. |
| Cumulative Days in the Hospital for Heart Failure | 12 months post-implant | The endpoint for this objective was defined as the cumulative days in hospital for heart failure (HF) expressed as a percentage of hospital free follow-up days during the 12-month randomized period. The relatedness of the events was based on the primary reason for which the subject was originally admitted to the hospital or seen in the emergency department or at an urgent visit, not on the development of new events that occur during hospitalization. |
| Characterize NYHA Functional Class | baseline to 12 months post implant | The outcome is the change in NYHA functional class between the baseline visit and the 12-month follow-up visit. At baseline subjects were required to be NYHA functional class II or III. The outcome will show the percentage of subjects that were functional class II and III at baseline and functional class I, II, III, or IV at the 12-month visit. The percent improvement from baseline is calculated as the percentage of subjects with a lower NYHA functional class at the 12-month visit compared to their NHYA functional class at baseline. |
| Characterize Distance Walked in Six Minutes | baseline to 12 months post implant | The outcome is the change in distance walked in 6-minutes in meters between the baseline visit and the 12-month follow-up visit. The change in distance walked was calculated within each subject as the distance walked in 6-minutes at the 12-month visit minus the distance walked in 6-minutes at the baseline visit. Positive values indicate an increase in the distance walked in 6-minutes from baseline. |
| Characterize Renal Function at the Baseline and 12-month Visit | baseline to 12 months post implant | Change in estimated glomerular filtration rate (eGFR) from baseline to the 12-month follow-up visit. eGFR was estimated using the MDRD forumula from the National Kidney Foundation (American Journal of Kidney Diseases 39: S1-299). Change in eGFR was computed as the 12-month eGFR value minus the baseline eGFR value. Positive values indicate an increase in eGFR from baseline and negative values indicate a decrease in eGFR from baseline. |
| Characterize Intracardiac Pressure Monitoring Following Defibrillation Testing (Chronicle ICD Subjects Only) | implant | Intracardiac pressure monitoring was deemed successful following defibrillation testing if physiological pressure waveforms were present following defibrillation testing. |
| Characterize Defibrillation Threshold Testing Efficacy (Chronicle ICD Subjects Only) | Implant | The outcome measure is the percentage of subjects implanted with the Chronicle ICD who completed defibrillation testing and had a 10 Joule safety margin |
| Characterize Quality of Life at Baseline and 12-month Visit | baseline to 12 months post implant | The outcome is the change in the Minnesota Living with Heart Failure® (MNLWHF) questionnaire response from baseline to the 12-month follow-up visit. The MNLWHF questionnaire is a 21 question questionnaire scored from zero (no impact of heart failure) to 5 (severe impact of heart failure). The composite MNLWHF score ranges from 0 (no impact of heart failure) to 105 (severe impact of heart failure). Change in MNLWHF score was computed as the 12-month minus the baseline score. |
| Characterize Arrhythmic Events | 12 months post implant | The rate of spontaneous VT (ventricular tachycardia)/VF (ventricular fibrillation) episodes during the 12-month follow-up period in episodes per subject month was compared between the Treatment Arm and the Control Arm |
| Characterize Intracardiac Pressure Changes in Response to Subject Clinical Signs and Symptoms of Heart Failure Events | 12 months post implant | The average daily median estimated pulmonary arterial diastolic pressure (ePAD) was computed for each subject with at least 90 days of ePAD data available and compared between the Control Arm subjects with and without a heart failure related event during the 12-month randomized period. |
| Relative Risk Reduction of Cardiovascular Related Events in the Treatment Group Compared to the Control Group | 12 months post-implant | The rate of CV-related events (hospitalizations \>24h, hospitalizations \<24h with IV therapy, ED visits with IV therapy, and urgent clinic visits with IV therapy) during the 12-month randomized follow-up period was compared between the Chronicle and Control groups. |
| Freedom From All Cause Death or Heart Failure Hospitalization | 12 months post-implant | Death from any cause or heart failure related hospitalization greater than 24 hours during the 12-month randomized period |
Countries
United States
Participant flow
Recruitment details
Recruitment began on April 28, 2006 and ended on January 14, 2011. All subjects were exited from the study on January 14, 2011. Fifty-three US clinical centers participated in the REDUCEhf study.
Pre-assignment details
Enrolled subjects were required to have a successful implant of the Chronicle® device prior to randomization. 407 subjects had an attempted implant of the Chronicle® ICD (Implantable Cardioverter Defibrillator) (406) or Chronicle IHM (Implantable Hemodynamic Monitor) (1 subject). Of these 407 subjects, 400 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm Physicians have access to device-based hemodynamic monitor information to guide patient management | 202 |
| Control Arm Physicians do not have access to device-based hemodynamic monitor information to guide patient management | 198 |
| Total | 400 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Long-term Follow-up | Death | 14 | 11 |
| Long-term Follow-up | Lost to Follow-up | 1 | 0 |
| Long-term Follow-up | Physician Decision | 127 | 122 |
| Long-term Follow-up | Study Closed | 29 | 34 |
| Long-term Follow-up | Withdrawal by Subject | 9 | 9 |
| Randomized Study Period | Death | 7 | 9 |
| Randomized Study Period | Lost to Follow-up | 4 | 0 |
| Randomized Study Period | Physician Decision | 6 | 10 |
| Randomized Study Period | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Treatment Arm | Control Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 51 Participants | 54 Participants | 105 Participants |
| Age, Categorical Between 18 and 65 years | 151 Participants | 144 Participants | 295 Participants |
| Age Continuous | 54.8 years STANDARD_DEVIATION 14.7 | 54.7 years STANDARD_DEVIATION 14.8 | 54.7 years STANDARD_DEVIATION 14.7 |
| NYHA (New York Heart Association) Classification NYHA Class II | 107 participants | 90 participants | 197 participants |
| NYHA (New York Heart Association) Classification NYHA Class III | 95 participants | 108 participants | 203 participants |
| Region of Enrollment United States | 202 participants | 198 participants | 400 participants |
| Sex: Female, Male Female | 61 Participants | 65 Participants | 126 Participants |
| Sex: Female, Male Male | 141 Participants | 133 Participants | 274 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 24 / 202 | 25 / 198 | 0 / 42 |
| serious Total, serious adverse events | 123 / 202 | 136 / 198 | 8 / 42 |
Outcome results
Primary
Percent of Subjects With an Attempted Chronicle IHM Implant Free From Chronicle IHM System-related Complications at 6-months Post-implant
A Chronicle IHM system-related complication was defined as any system-related adverse event that occurred during the clinical investigation which is (1) treated with invasive means (including intravenous drug therapy), (2) results in death or serious injury of subject, (3) results in the explant of any Chronicle IHM component,and/or (4) causes permanent loss of significant function of the implanted system.
Time frame: 6 months post implant
Population: All subjects with an attempted implant of the Chronicle IHM system were included in this analysis. At the time the study stopped, there was only one subject with an attempted Chronicle IHM implant. Thus this objective was not analyzed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chronicle ICD Implanted Subjects | Percent of Subjects With an Attempted Chronicle IHM Implant Free From Chronicle IHM System-related Complications at 6-months Post-implant | 100 Percent of Chronicle IHM subjects |
Primary
Percent of Subjects With an Attempted Implant of the Chronicle ICD System Free From System-related Chronicle ICD Complications at 6-months Post-implant.
A Chronicle ICD system-related complication was defined as any system-related adverse event that occurred during the clinical investigation which is (1) treated with invasive means (including intravenous drug therapy), (2) results in death or serious injury of subject, (3) results in the explant of any Chronicle ICD component,and/or (4) causes permanent loss of significant function of the implanted system.
Time frame: Within 6 months post-implant
Population: All 406 subjects with an attempted implant of the Chronicle ICD system.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chronicle ICD Implanted Subjects | Percent of Subjects With an Attempted Implant of the Chronicle ICD System Free From System-related Chronicle ICD Complications at 6-months Post-implant. | 90.5 Percentage of Chronicle ICD Subjects |
Comparison: Null hypothesis: Freedom from Chronicle system-related complications at 6-months post-implant is less than or equal to 80%.~Alternative hypothesis: Freedom from Chronicle system-related complications at 6-months is greater than 80%.p-value: <0.001Survival estimate at 6-months
Primary
Relative Risk Reduction of All Heart Failure Related Events in the Treatment Group Compared to the Control Group
The rate of HF-related events (hospitalizations \>24h, hospitalizations \<24h with IV therapy, ED visits with IV therapy, and urgent clinic visits with IV therapy) during the 12-month randomized follow-up period was compared between the Chronicle and Control groups.
Time frame: 12 months post-implant
Population: All randomized subjects
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chronicle ICD Implanted Subjects | Relative Risk Reduction of All Heart Failure Related Events in the Treatment Group Compared to the Control Group | 0.48 Heart failure related events per year |
| Control Arm | Relative Risk Reduction of All Heart Failure Related Events in the Treatment Group Compared to the Control Group | 0.49 Heart failure related events per year |
Comparison: The study was originally powered at 80% to detect a 25% risk reduction between the treatment arm and control arm with a type I error rate of 0.05. Under these assumptions 648 HF-related events from approximately 1300 subjects were required. The study stopped after 400 were randomized.~Null Hypothesis: The HF-related event rate is the same between the treatment arm and control arm.~Alternative Hypothesis: The HF-related event rate between the treatment arm and control arm is different.p-value: 0.97895% CI: [0.61, 1.61]Andersen-Gill
Secondary
Characterize Arrhythmic Events
The rate of spontaneous VT (ventricular tachycardia)/VF (ventricular fibrillation) episodes during the 12-month follow-up period in episodes per subject month was compared between the Treatment Arm and the Control Arm
Time frame: 12 months post implant
Population: All 399 subjects successfully implanted with the Chronicle ICD were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chronicle ICD Implanted Subjects | Characterize Arrhythmic Events | 0.54 VT/VF episodes per subject month |
| Control Arm | Characterize Arrhythmic Events | 0.38 VT/VF episodes per subject month |
Comparison: Null Hypothesis: Rate of VT/VF episodes during the 12-month randomized period is the same between the Treatment Arm and the Control Arm.~Alternative Hypothesis: Rate of VT/VF episodes during the 12-month randomized period is different between the Treatment Arm and the Control Arm.p-value: 0.36895% CI: [0.63, 3.5]Andersen-Gill Model
Secondary
Characterize Defibrillation Threshold Testing Efficacy (Chronicle ICD Subjects Only)
The outcome measure is the percentage of subjects implanted with the Chronicle ICD who completed defibrillation testing and had a 10 Joule safety margin
Time frame: Implant
Population: Of the 406 subjects with an attempted implant of the Chronicle ICD system, 366 completed defibrillation testing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chronicle ICD Implanted Subjects | Characterize Defibrillation Threshold Testing Efficacy (Chronicle ICD Subjects Only) | 98.9 percentage of subjects |
Secondary
Characterize Distance Walked in Six Minutes
The outcome is the change in distance walked in 6-minutes in meters between the baseline visit and the 12-month follow-up visit. The change in distance walked was calculated within each subject as the distance walked in 6-minutes at the 12-month visit minus the distance walked in 6-minutes at the baseline visit. Positive values indicate an increase in the distance walked in 6-minutes from baseline.
Time frame: baseline to 12 months post implant
Population: Subjects were required to complete the 6-minute hall walk test at both the baseline and 12-month visit to be included in the analysis of this objective.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronicle ICD Implanted Subjects | Characterize Distance Walked in Six Minutes | Baseline visit | 313.2 distance walked in 6-minutes (meters) | Standard Deviation 124.8 |
| Chronicle ICD Implanted Subjects | Characterize Distance Walked in Six Minutes | 12-month visit | 354.5 distance walked in 6-minutes (meters) | Standard Deviation 178.8 |
| Chronicle ICD Implanted Subjects | Characterize Distance Walked in Six Minutes | Change from baseline to 12-months | 41.3 distance walked in 6-minutes (meters) | Standard Deviation 160.5 |
| Control Arm | Characterize Distance Walked in Six Minutes | Baseline visit | 308.7 distance walked in 6-minutes (meters) | Standard Deviation 133.5 |
| Control Arm | Characterize Distance Walked in Six Minutes | 12-month visit | 347.2 distance walked in 6-minutes (meters) | Standard Deviation 160.4 |
| Control Arm | Characterize Distance Walked in Six Minutes | Change from baseline to 12-months | 38.5 distance walked in 6-minutes (meters) | Standard Deviation 154.3 |
Comparison: Null Hypothesis: The change in 6-minute hall walk distance is not different between the Treatment and Control Arms.~Alternative Hypothesis: The change in 6-minute hall walk distance is different between the Treatment and Control Arms.p-value: 0.996Mixed Models Analysis
Secondary
Characterize Health Resource Utilization
Percentage of randomized days spent in the intensive care unit for heart failure. Reason for hospitalization was determined by the adverse event adjudication committee.
Time frame: 12 months post implant
Population: All randomized subjects.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chronicle ICD Implanted Subjects | Characterize Health Resource Utilization | 0.1 percentage of randomized days |
| Control Arm | Characterize Health Resource Utilization | 0.4 percentage of randomized days |
Secondary
Characterize Intracardiac Pressure
The average daily median estimated pulmonary arterial diastolic pressure (ePAD) was computed for each subject with at least 90 days of ePAD data available and compared between the Treatment and Control arms.
Time frame: 12 months post implant
Population: At least 90 days of ePAD data were required for each subject during the 12-month randomized period to be included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronicle ICD Implanted Subjects | Characterize Intracardiac Pressure | 22.0 ePAD mm Hg | Standard Deviation 5.6 |
| Control Arm | Characterize Intracardiac Pressure | 23.3 ePAD mm Hg | Standard Deviation 6.5 |
Comparison: Null hypothesis: Average daily median ePAD is the same between the Treatment and Control arms.~Alternative hypothesis: Average daily median ePAD is the different between the Treatment and Control arms.p-value: 0.033t-test, 2 sided
Secondary
Characterize Intracardiac Pressure Changes in Response to Subject Clinical Signs and Symptoms of Heart Failure Events
The average daily median estimated pulmonary arterial diastolic pressure (ePAD) was computed for each subject with at least 90 days of ePAD data available and compared between the Control Arm subjects with and without a heart failure related event during the 12-month randomized period.
Time frame: 12 months post implant
Population: All Control Arm subjects with at least 90 days of pressure data available during the 12-month randomized follow-up period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronicle ICD Implanted Subjects | Characterize Intracardiac Pressure Changes in Response to Subject Clinical Signs and Symptoms of Heart Failure Events | 26.3 ePAD mm Hg | Standard Deviation 6.5 |
| Control Arm | Characterize Intracardiac Pressure Changes in Response to Subject Clinical Signs and Symptoms of Heart Failure Events | 22.5 ePAD mm Hg | Standard Deviation 6.3 |
Comparison: Null Hypothesis: The average daily median ePAD is not different among Control Arm subjects that have and that do not have a heart failure related event during the 12-month follow-up period.~Alternative Hypothesis: The average daily median ePAD is different among Control Arm subjects that have and that do not have a heart failure related event during the 12-month follow-up period.p-value: 0.002t-test, 2 sided
Secondary
Characterize Intracardiac Pressure Monitoring Following Defibrillation Testing (Chronicle ICD Subjects Only)
Intracardiac pressure monitoring was deemed successful following defibrillation testing if physiological pressure waveforms were present following defibrillation testing.
Time frame: implant
Population: Of the 406 subjects with an attempted implant of the Chronicle ICD system, 366 completed defibrillation testing as part of their ICD implant procedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chronicle ICD Implanted Subjects | Characterize Intracardiac Pressure Monitoring Following Defibrillation Testing (Chronicle ICD Subjects Only) | 99.7 Percentage of subjects with waveforms |
Secondary
Characterize Medication Usage
The rate of change of cardiovascular medications in changes per subject month were computed and compared between treatment groups.
Time frame: 12 months post implant
Population: All randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chronicle ICD Implanted Subjects | Characterize Medication Usage | 1.77 Medication changes per subject month |
| Control Arm | Characterize Medication Usage | 1.49 Medication changes per subject month |
Comparison: The null hypothesis is that the rate of cardiovascular medication changes is the same between the Treatment Arm and Control Arm.p-value: 0.145Negative-Binomial Regression
Secondary
Characterize NYHA Functional Class
The outcome is the change in NYHA functional class between the baseline visit and the 12-month follow-up visit. At baseline subjects were required to be NYHA functional class II or III. The outcome will show the percentage of subjects that were functional class II and III at baseline and functional class I, II, III, or IV at the 12-month visit. The percent improvement from baseline is calculated as the percentage of subjects with a lower NYHA functional class at the 12-month visit compared to their NHYA functional class at baseline.
Time frame: baseline to 12 months post implant
Population: Subjects were required to have an NYHA functional class assessment at the baseline and 12-month follow-up visit to be included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chronicle ICD Implanted Subjects | Characterize NYHA Functional Class | Percent Subjects NYHA Class III Baseline | 45 percentage of subjects |
| Chronicle ICD Implanted Subjects | Characterize NYHA Functional Class | Percent Subjects NYHA Class IV Month 12 | 2 percentage of subjects |
| Chronicle ICD Implanted Subjects | Characterize NYHA Functional Class | Percent Subjects NYHA Class II Month 12 | 46 percentage of subjects |
| Chronicle ICD Implanted Subjects | Characterize NYHA Functional Class | Percent Subjects Improved NYHA Class | 44 percentage of subjects |
| Chronicle ICD Implanted Subjects | Characterize NYHA Functional Class | Percent Subjects NYHA Class I Month 12 | 24 percentage of subjects |
| Chronicle ICD Implanted Subjects | Characterize NYHA Functional Class | Percent Subjects No Change in NYHA Class | 45 percentage of subjects |
| Chronicle ICD Implanted Subjects | Characterize NYHA Functional Class | Percent Subjects NYHA Class III Month 12 | 27 percentage of subjects |
| Chronicle ICD Implanted Subjects | Characterize NYHA Functional Class | Percent Subjects Worsened NYHA Class | 12 percentage of subjects |
| Chronicle ICD Implanted Subjects | Characterize NYHA Functional Class | Percent Subjects NYHA Class II Baseline | 55 percentage of subjects |
| Control Arm | Characterize NYHA Functional Class | Percent Subjects Worsened NYHA Class | 10 percentage of subjects |
| Control Arm | Characterize NYHA Functional Class | Percent Subjects NYHA Class II Baseline | 48 percentage of subjects |
| Control Arm | Characterize NYHA Functional Class | Percent Subjects NYHA Class III Baseline | 52 percentage of subjects |
| Control Arm | Characterize NYHA Functional Class | Percent Subjects NYHA Class I Month 12 | 17 percentage of subjects |
| Control Arm | Characterize NYHA Functional Class | Percent Subjects NYHA Class II Month 12 | 52 percentage of subjects |
| Control Arm | Characterize NYHA Functional Class | Percent Subjects NYHA Class III Month 12 | 28 percentage of subjects |
| Control Arm | Characterize NYHA Functional Class | Percent Subjects NYHA Class IV Month 12 | 5 percentage of subjects |
| Control Arm | Characterize NYHA Functional Class | Percent Subjects Improved NYHA Class | 41 percentage of subjects |
| Control Arm | Characterize NYHA Functional Class | Percent Subjects No Change in NYHA Class | 49 percentage of subjects |
Comparison: Null Hypothesis: There is no difference in the change in NYHA functional class between the Treatment and Control Arms.~Alternative Hypothesis: There is a difference in the change in NYHA functional class between the Treatment and Control Arms.p-value: 0.29295% CI: [0.82, 1.96]Proportional odds regression model
Secondary
Characterize Quality of Life at Baseline and 12-month Visit
The outcome is the change in the Minnesota Living with Heart Failure® (MNLWHF) questionnaire response from baseline to the 12-month follow-up visit. The MNLWHF questionnaire is a 21 question questionnaire scored from zero (no impact of heart failure) to 5 (severe impact of heart failure). The composite MNLWHF score ranges from 0 (no impact of heart failure) to 105 (severe impact of heart failure). Change in MNLWHF score was computed as the 12-month minus the baseline score.
Time frame: baseline to 12 months post implant
Population: Subjects were required to respond to the baseline and 12-month follow-up visit to be included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronicle ICD Implanted Subjects | Characterize Quality of Life at Baseline and 12-month Visit | Baseline MNWHF score | 49.7 scores on a scale | Standard Deviation 26.4 |
| Chronicle ICD Implanted Subjects | Characterize Quality of Life at Baseline and 12-month Visit | 12-month MNWHF score | 34.0 scores on a scale | Standard Deviation 25.6 |
| Chronicle ICD Implanted Subjects | Characterize Quality of Life at Baseline and 12-month Visit | Change in MNWHF score from baseline | -15.7 scores on a scale | Standard Deviation 27.3 |
| Control Arm | Characterize Quality of Life at Baseline and 12-month Visit | Baseline MNWHF score | 52.7 scores on a scale | Standard Deviation 28 |
| Control Arm | Characterize Quality of Life at Baseline and 12-month Visit | 12-month MNWHF score | 37.2 scores on a scale | Standard Deviation 25.9 |
| Control Arm | Characterize Quality of Life at Baseline and 12-month Visit | Change in MNWHF score from baseline | -15.6 scores on a scale | Standard Deviation 23.7 |
Comparison: Null Hypothesis: There is no difference in the change in MNLWHF score from baseline to 12-months between the Treatment Arm and Control Arm.~Alternative Hypothesis: There is a difference in the change in MNLWHF score from baseline to 12-months between the Treatment Arm and Control Arm.p-value: 0.583Mixed Models Analysis
Secondary
Characterize Randomized Days Alive Out of Hospital
Randomized days alive outside of the hospital was computed for each subject as the total number of randomized days minus the number of randomized days spent in the hospital for any cause.
Time frame: 12 months post implant
Population: All randomized subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronicle ICD Implanted Subjects | Characterize Randomized Days Alive Out of Hospital | 340 Days | Standard Deviation 65 |
| Control Arm | Characterize Randomized Days Alive Out of Hospital | 341 Days | Standard Deviation 63 |
Secondary
Characterize Renal Function at the Baseline and 12-month Visit
Change in estimated glomerular filtration rate (eGFR) from baseline to the 12-month follow-up visit. eGFR was estimated using the MDRD forumula from the National Kidney Foundation (American Journal of Kidney Diseases 39: S1-299). Change in eGFR was computed as the 12-month eGFR value minus the baseline eGFR value. Positive values indicate an increase in eGFR from baseline and negative values indicate a decrease in eGFR from baseline.
Time frame: baseline to 12 months post implant
Population: Subjects were required to have creatinine values available at the baseline and 12-month visit to be included in the analysis of this objective.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronicle ICD Implanted Subjects | Characterize Renal Function at the Baseline and 12-month Visit | Baseline eGFR | 72.4 mL/min/1.73 m^2 | Standard Deviation 26.2 |
| Chronicle ICD Implanted Subjects | Characterize Renal Function at the Baseline and 12-month Visit | 12-month eGFR | 68.6 mL/min/1.73 m^2 | Standard Deviation 27.7 |
| Chronicle ICD Implanted Subjects | Characterize Renal Function at the Baseline and 12-month Visit | Change in eGFR from baseline to 12-months | -3.8 mL/min/1.73 m^2 | Standard Deviation 22 |
| Control Arm | Characterize Renal Function at the Baseline and 12-month Visit | Baseline eGFR | 69.8 mL/min/1.73 m^2 | Standard Deviation 20.4 |
| Control Arm | Characterize Renal Function at the Baseline and 12-month Visit | 12-month eGFR | 69.2 mL/min/1.73 m^2 | Standard Deviation 25.6 |
| Control Arm | Characterize Renal Function at the Baseline and 12-month Visit | Change in eGFR from baseline to 12-months | -0.6 mL/min/1.73 m^2 | Standard Deviation 19.3 |
Comparison: Null Hypothesis: The change from baseline to the 12-month follow-up visit in eGFR values is the same between the Treatment arm and Control arm.~Alternative Hypothesis: The change from baseline to the 12-month follow-up visit in eGFR values is different between the Treatment arm and Control arm.p-value: 0.154Mixed Models Analysis
Secondary
Characterize Subject Survival
Death from any cause during the 12-month randomization period
Time frame: 12 months post implant
Population: All randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chronicle ICD Implanted Subjects | Characterize Subject Survival | 7 number of deaths |
| Control Arm | Characterize Subject Survival | 9 number of deaths |
Comparison: Null hypothesis: Survival during the 12-month randomized follow-up period is the same between the treatment and control groups.~Alternative hypothesis: Survival during the 12-month randomized period is different between the treatment and control groups.p-value: 0.59995% CI: [0.29, 2.06]Regression, Cox
Secondary
Cumulative Days in the Hospital for Heart Failure
The endpoint for this objective was defined as the cumulative days in hospital for heart failure (HF) expressed as a percentage of hospital free follow-up days during the 12-month randomized period. The relatedness of the events was based on the primary reason for which the subject was originally admitted to the hospital or seen in the emergency department or at an urgent visit, not on the development of new events that occur during hospitalization.
Time frame: 12 months post-implant
Population: All follow-up from all randomized subjects were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chronicle ICD Implanted Subjects | Cumulative Days in the Hospital for Heart Failure | 0 Percent days in hospital |
| Control Arm | Cumulative Days in the Hospital for Heart Failure | 0 Percent days in hospital |
Comparison: Null Hypothesis: mu(Treatment) = mu(Control) Alternative Hypothesis: mu(Treatment) ne mu(Control)~where mu is the percentage of hospitalized days for heart failure.p-value: 0.574Wilcoxon (Mann-Whitney)
Secondary
Freedom From All Cause Death or Heart Failure Hospitalization
Death from any cause or heart failure related hospitalization greater than 24 hours during the 12-month randomized period
Time frame: 12 months post-implant
Population: All randomized subjects
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chronicle ICD Implanted Subjects | Freedom From All Cause Death or Heart Failure Hospitalization | 42 Number of subjects meeting endpoint |
| Control Arm | Freedom From All Cause Death or Heart Failure Hospitalization | 47 Number of subjects meeting endpoint |
Comparison: Null Hypothesis: Freedom from death or HF-related hospitalization is the same between the treatment arm and the control arm.~Alternative Hypothesis: Freedom from death or HF-related hospitalization is different between the treatment arm and the control arm.p-value: 0.50595% CI: [0.57, 1.32]Regression, Cox
Secondary
Percentage of Randomized Subjects at Each Level of the Composite Response Endpoint Between the Treatment Arm and the Control Arm.
The definitions of worsened, improved, and unchanged are as follows: Worsened: Subject dies, is hospitalized for worsening heart failure, permanently discontinues blinded randomized assignment and has worsening heart failure at time of study discontinuation, demonstrates worsening NYHA Class at LOCF, or moderate-marked worsening of global assessment score at LOCF. Improved: Subject has not worsened, and demonstrates improvement in NYHA class and/or moderate-marked improvement in subject global assessment score. Unchanged: Subject is neither worsened nor improved.
Time frame: 12 months post implant
Population: All randomized follow-up from all randomized subjects were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chronicle ICD Implanted Subjects | Percentage of Randomized Subjects at Each Level of the Composite Response Endpoint Between the Treatment Arm and the Control Arm. | Percent Subjects Improved | 51 Percent of Subjects |
| Chronicle ICD Implanted Subjects | Percentage of Randomized Subjects at Each Level of the Composite Response Endpoint Between the Treatment Arm and the Control Arm. | Percent Subjects Unchanged | 19 Percent of Subjects |
| Chronicle ICD Implanted Subjects | Percentage of Randomized Subjects at Each Level of the Composite Response Endpoint Between the Treatment Arm and the Control Arm. | Percent Subjects Worsened | 30 Percent of Subjects |
| Control Arm | Percentage of Randomized Subjects at Each Level of the Composite Response Endpoint Between the Treatment Arm and the Control Arm. | Percent Subjects Improved | 51 Percent of Subjects |
| Control Arm | Percentage of Randomized Subjects at Each Level of the Composite Response Endpoint Between the Treatment Arm and the Control Arm. | Percent Subjects Unchanged | 17 Percent of Subjects |
| Control Arm | Percentage of Randomized Subjects at Each Level of the Composite Response Endpoint Between the Treatment Arm and the Control Arm. | Percent Subjects Worsened | 32 Percent of Subjects |
Comparison: Null Hypothesis: Distribution of composite response endpoint is the same between the treatment arm and the control arm.~Alternative Hypothesis: Distribution of composite response endpoint is different between the treatment arm and the control arm.p-value: 0.75895% CI: [0.73, 1.54]Proportional odds model
Secondary
Relative Risk of All-cause Events
All-cause events were defined as hospitalizations, hospitalizations \<24 hours necessitating intravenous therapy, emergency department visits necessitating intravenous therapy or urgent visits necessitating intravenous therapy.
Time frame: 12 months post-implant
Population: All randomized follow-up from all randomized subjects
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chronicle ICD Implanted Subjects | Relative Risk of All-cause Events | 1.18 All cause event rate per year |
| Control Arm | Relative Risk of All-cause Events | 1.55 All cause event rate per year |
Comparison: Null Hypothesis: The all cause event rate is the same between the treatment arm and control arm.~Alternative Hypothesis: The all cause event rate between the treatment arm and control arm is different.p-value: 0.08895% CI: [0.56, 1.04]Andersen-Gill Model
Secondary
Relative Risk Reduction of Cardiovascular Related Events in the Treatment Group Compared to the Control Group
The rate of CV-related events (hospitalizations \>24h, hospitalizations \<24h with IV therapy, ED visits with IV therapy, and urgent clinic visits with IV therapy) during the 12-month randomized follow-up period was compared between the Chronicle and Control groups.
Time frame: 12 months post-implant
Population: All randomized follow-up for all randomized subjects.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chronicle ICD Implanted Subjects | Relative Risk Reduction of Cardiovascular Related Events in the Treatment Group Compared to the Control Group | 0.77 Cardiovascular related events per year |
| Control Arm | Relative Risk Reduction of Cardiovascular Related Events in the Treatment Group Compared to the Control Group | 0.86 Cardiovascular related events per year |
Comparison: Null Hypothesis: The CV-related event rate is the same between the treatment arm and control arm.~Alternative Hypothesis: The CV-related event rate between the treatment arm and control arm is different.p-value: 0.52795% CI: [0.62, 1.28]Andersen-Gill Model