Heart Failure
Conditions
Brief summary
This study will look at different pacing modes (how a device is programmed to pace one's heart), and how these modes may assist in one's daily activities and how one is feeling.
Detailed description
PEGASUS CRT is a multicenter trial that will assess the effect of a cardiac resynchronization therapy defibrillator (CRT-D) device programmed to DDD-70 or DDDR-40 compared to a CRT device programmed to DDD-40 in heart failure patients. The effect of atrial support pacing in heart failure patients will be assessed using a clinical composite rating. A sub-study will evaluate the effect pacing mode has on exercise capacity in this heart failure population.
Interventions
DEVICEAtrial support pacing through cardiac resynchronization therapy. Device: RENEWAL family of CRT-D devices
All subjects in this trial receive the same device. For the purpose of this trial, intervention is programming mode and lower rate limit to deliver atrial support pacing in the two treatment arms, while the control arm will receive programming where limited atrial support pacing is delivered. DDD-70 and DDDR-40 are the treatment arms programmed to receive atrial support pacing and will be compared to the DDD-40 arm.
Sponsors
Boston Scientific Corporation
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
* Patients who meet current indications for the CONTAK RENEWAL® family of cardiac resynchronization therapy defibrillator (CRT-D) devices or future Food and Drug Administration (FDA) approved Guidant CRT-D devices * Patients who sign and date a Patient Informed Consent at, or prior to, the implant visit * Patients who are in sinus rhythm at the time of implant * Patients who remain in the clinical care of the enrolling physician in approved centers * Patients who are on optimal pharmacologic therapy or who have developed a recent implantable cardioverter defibrillator (ICD) indication that necessitates ICD therapy concurrent with the optimization of pharmacologic therapy
Exclusion criteria
* Patients whose medical condition is expected to preclude the use of the protocol-required pacing mode (dual chamber pacing \[DDD or DDDR\]) and respective lower rate limits * Patients with permanent atrial fibrillation or atrial flutter * Patients who are in complete heart block * Patients who have previously had a pacemaker, ICD, or CRT device * Patients whose life expectancy is less than 12 months due to other medical conditions * Patients who are expected to receive a heart transplant during the duration of the study * Patients who have other cardiac surgeries or procedures planned but not yet performed * Patients who currently have or who are likely to receive a tricuspid valve prosthesis * Patients who are currently enrolled in another investigational study or registry that would directly impact the treatment or outcome of the current study. * Patients who are younger than 18 years of age * Patients who are mentally incompetent and cannot sign a Patient Informed Consent form or comply with the study * Patients who are or become pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Composite Score | From randomization (6-weeks) through 12-month visit | The primary outcome measure classified patients as improved, unchanged or worsened, based on a 4 components clinical composite score using the following four components: death, heart failure hospitalization, New York Heart Association \[NYHA\] class, patient's Global Assessment rating. Best value is improved, whereas worst value is worsened. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life | From randomization (6-weeks) through 12-month visit | Quality of Life as assessed by the Minnesota Living with Heart Failure Questionniare for those patients with paired data at 6 weeks and 12 months. This score is on a scale of 0(best)- 105(worst). A negative change denotes improvement. |
| Change in Self Assessed Physical Activity | From randomization (6-weeks) through 12-month visit | Physical activity was assessed using the Physical Activity Scale of the Elderly (PASE) questionnaire for those patients with paired data available at the 6 week and 12 month visits. The PASE is designed to assess physical activity in older persons. The total PASE score was computed by multiplying the amount of time spent in each activity (hours/week) or participation (yes/no) in an activity by empirically derived item weights and summing over all activities. PASE scores for this study ranged from 0 to 756 with higher scores indicating more physical activity. |
Countries
United States
Participant flow
Recruitment details
Enrollment began on November 8, 2004, was completed on December 21, 2007, with study follow-up commencing January 30, 2009. This trial was conducted at institutional settings throughout the United States and Australia.
Pre-assignment details
All patients with successful system implants were programmed to DDD-40 (atrial rate support above 40 bpm; limited atrial pacing) for the first 6-weeks of the trial. Randomization (1:1:1 allocation) occurred after patients had reached the 6-week visit and continued to meet all of the eligibility criteria for the trial.
Participants by arm
| Arm | Count |
|---|---|
| DDD-40 Atrial Tracking (atrial rate support above 40 bpm) | 475 |
| DDD-70 Atrial Rate Support (atrial rate support above 70 bpm) | 488 |
| DDDR-40 Rate Adaptive Pacing (atrial rate support above 40 bpm with rate responsive pacing) | 470 |
| Total | 1,433 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Post-randomization | Lost to Follow-up | 12 | 15 | 12 |
| Post-randomization | Withdrawn | 26 | 32 | 27 |
| Pre-randomization | Death | 19 | 0 | 0 |
| Pre-randomization | Lost to Follow-up | 70 | 0 | 0 |
| Pre-randomization | Physician Decision | 8 | 0 | 0 |
| Pre-randomization | Protocol Violation | 172 | 0 | 0 |
| Pre-randomization | Withdrawal by Subject | 40 | 0 | 0 |
Baseline characteristics
| Characteristic | DDD-40 | DDD-70 | DDDR-40 | Total |
|---|---|---|---|---|
| Age Continuous | 67.3 years STANDARD_DEVIATION 11.4 | 67.5 years STANDARD_DEVIATION 10.4 | 66.7 years STANDARD_DEVIATION 11.6 | 67.2 years STANDARD_DEVIATION 11.1 |
| Sex: Female, Male Female | 165 Participants | 156 Participants | 165 Participants | 486 Participants |
| Sex: Female, Male Male | 310 Participants | 332 Participants | 305 Participants | 947 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 | 129 / 475 | 119 / 488 | 112 / 470 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Clinical Composite Score
The primary outcome measure classified patients as improved, unchanged or worsened, based on a 4 components clinical composite score using the following four components: death, heart failure hospitalization, New York Heart Association \[NYHA\] class, patient's Global Assessment rating. Best value is improved, whereas worst value is worsened.
Time frame: From randomization (6-weeks) through 12-month visit
Population: This analysis is intention to treat (ITT) in terms of patient's being analyzed according to their randomized group. Last observation carried forward (LOCF) method was used for missing NYHA and global assessment measures at 12 months.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DDD-40 | Clinical Composite Score | Worsened | 123 participants |
| DDD-40 | Clinical Composite Score | Improved | 230 participants |
| DDD-40 | Clinical Composite Score | Unchanged | 84 participants |
| DDD-70 | Clinical Composite Score | Unchanged | 94 participants |
| DDD-70 | Clinical Composite Score | Worsened | 112 participants |
| DDD-70 | Clinical Composite Score | Improved | 235 participants |
| DDDR-40 | Clinical Composite Score | Improved | 229 participants |
| DDDR-40 | Clinical Composite Score | Worsened | 117 participants |
| DDDR-40 | Clinical Composite Score | Unchanged | 85 participants |
Comparison: One sided test testing for shift towards improvement in either atrial support pacing treatment arm compared to the DDD-40 arm.p-value: 0.55Cochran-Armitage test for trend
p-value: 0.8Cochran-Armitage test for trend
Secondary
Change in Quality of Life
Quality of Life as assessed by the Minnesota Living with Heart Failure Questionniare for those patients with paired data at 6 weeks and 12 months. This score is on a scale of 0(best)- 105(worst). A negative change denotes improvement.
Time frame: From randomization (6-weeks) through 12-month visit
Population: Quality of Life was analyzed for those patients with paired data available at the 6 week and 12 month visit. Patients were analyzed in their randomized groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DDD-40 | Change in Quality of Life | -2.97 units on a scale | Standard Deviation 24.18 |
| DDD-70 | Change in Quality of Life | -3.27 units on a scale | Standard Deviation 22.77 |
| DDDR-40 | Change in Quality of Life | -4.46 units on a scale | Standard Deviation 25.43 |
Comparison: The changes in quality of life were compared between groups using two-sided t-tests.p-value: 0.8695% CI: [-3.14, 3.74]t-test, 2 sided
Comparison: The difference in changes in quality of life between groups were compared using a t-test.p-value: 0.4395% CI: [-2.18, 5.16]t-test, 2 sided
Secondary
Change in Self Assessed Physical Activity
Physical activity was assessed using the Physical Activity Scale of the Elderly (PASE) questionnaire for those patients with paired data available at the 6 week and 12 month visits. The PASE is designed to assess physical activity in older persons. The total PASE score was computed by multiplying the amount of time spent in each activity (hours/week) or participation (yes/no) in an activity by empirically derived item weights and summing over all activities. PASE scores for this study ranged from 0 to 756 with higher scores indicating more physical activity.
Time frame: From randomization (6-weeks) through 12-month visit
Population: Physical activity was assessed using the Physical Activity Scale for the Elderly and was analyzed for those patients with paired data available at the 6 week and 12 month visit. Patients were analyzed in their randomized groups. Postive values for changes denote improvements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DDD-40 | Change in Self Assessed Physical Activity | 12.45 units on a scale | Standard Deviation 78.62 |
| DDD-70 | Change in Self Assessed Physical Activity | 22.62 units on a scale | Standard Deviation 88.86 |
| DDDR-40 | Change in Self Assessed Physical Activity | 25.69 units on a scale | Standard Deviation 92.41 |
Comparison: Compare the difference in the changes in physical activity scores between groups using a t-test.p-value: 0.1195% CI: [-22.65, 2.3]t-test, 2 sided
Comparison: Compare the difference in the changes in physical activity scores between groups using a t-test.~To adjust for multiple comparisons, an alpha level of 0.025 should be used to deem significance.p-value: 0.0495% CI: [-26.11, -0.37]t-test, 2 sided