Heart Failure
Conditions
Brief summary
The purpose of the study is to evaluate the benefit of interventricular (V-V) delay optimization in reducing the non-responder rate in patients with cardiac resynchronization defibrillator (CRT-D) devices. The primary endpoint of this study is CRT responder rate. For patients enrolled with new CRT-D systems, patients are considered non-responders if BOTH of the following requirements are fulfilled: * \< 10% improvement in 6-minute hall walk, and * no class improvement or worsening in New York Heart Association (NYHA) scale. For those receiving CRT-D devices as replacements of older CRT-D systems, patients are considered non-responders if BOTH of the following requirements are fulfilled: * \> 1 heart failure (HF) related hospitalization, and * no class improvement or worsening in NYHA scale.
Detailed description
Study Methods * This is a prospective, randomized (simultaneous biventricular (BiV) pacing vs. sequential BiV pacing) study. * Any patient that receives an FDA approved St. Jude Medical (SJM) CRT-D with V-V timing is eligible for enrollment. * At 3 months post enrollment (or at implant for CRT-D replacements), patients screened as non-responders are randomized to either simultaneous or sequential BiV pacing. Patients requiring a replacement CRT-D device that are identified as non-responders to CRT are enrolled at the screening/randomization visit. * Patients are followed for a period of 6 months post randomization: * Enrollment (1 week pre CRT-D implant to \< 2 weeks post CRT-D implant) * Screening/Randomization Visit (3 months post enrollment) * Follow-up Visit (6 months post randomization) * Total # of centers - 80 centers * Sample size - 800 patients screened for CRT non-responders
Interventions
DEVICESimultaneous VV Pacing
Right ventricular and left ventricular pacing delivered simultaneously.
DEVICESequential VV Pacing
Right ventricular and left ventricular pacing delivered sequentially.
Sponsors
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has a standard indication for a CRT-D. * Patient has the ability to complete a 6-minute hall walk with the only limiting factor to be fatigue or shortness of breath. * Patient is geographically stable and willing to comply with the required follow-up schedule. * Prior to 1 month of randomization, patient's HF medications are maintained stable and remain stable throughout the study. * Patients requiring a CRT-D replacement must comply with BOTH of the following: * \> 1 HF related hospitalization * No class improvement or worsening in NYHA scale
Exclusion criteria
* Patient's life expectancy is less than 12 months. * Patient has had cardiac surgery within 6 months of enrollment. * Patient has an epicardial ventricular lead system. * Patient is less than 18 years old. * Patient is pregnant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CRT Responder Rate | 6 months | Patients underwent baseline NYHA class and 6-minute hall walk distance (6-MHWD) assessment. After device implantation AV delays were optimized and all patients were programmed to simultaneous biventricular (BiV) pacing. At the 3-month follow-up, the NYHA class and 6-MHWD were reassessed. Non-responders were randomized 1:1 to either sequential BiV pacing with VV optimization or simultaneous BiV pacing. The responder rate at 6 months post randomization was compared between the two groups. Which is why the numbers are broken further down in the Outcome Measure table. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NYHA Class Progression | 6 months | New York Heart Association (NYHA) functional classification provides a way of classifying the extent of heart failure. It places patients in one of four categories based on how much they are limited during physical activity; the limitations/symptoms are in regard to normal breathing and varying degrees in shortness of breath and/or angina pain. |
| 6 Minute Hall Walk Distance Test (6-MHWD) | 6 months | Patients were considered non-responders if the 6-MHWD had not improved by greater than or equal to 10% compared to baseline. This statement is accurate and appropriate. |
| Left Ventricular Ejection Fraction (LVEF) | Randomization and 9 months | Ejection fraction is a measurement of the percentage of blood leaving your heart each time it contracts. The left ventricle is the heart's main pumping chamber, so ejection fraction is usually measured only in the left ventricle (LV). |
Countries
United States
Participant flow
Recruitment details
816 patients were enrolled in the trial. Of the patients screened at the 3-month follow up, 572 patients were classified as responders and 102 patients as non-responders.
Pre-assignment details
102 of the patients were non-responders, but only 93 were randomized of which 57 completed the study and had data available for analysis. of the 816 participants screened only 93 wre randomized to treatment. This statement is accurate and appropriate.
Participants by arm
| Arm | Count |
|---|---|
| Simultaneous Pacing V-V Timing Patients maintained on simultaneous V-V delay | 31 |
| Sequential VV Pacing V-V delay was optimized | 26 |
| Total | 57 |
Baseline characteristics
| Characteristic | Sequential VV Pacing | Simultaneous Pacing V-V Timing | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 18 Participants | 29 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 13 Participants | 28 Participants |
| Age, Continuous | 62.4 years STANDARD_DEVIATION 11.2 | 68.2 years STANDARD_DEVIATION 8 | 65.6 years STANDARD_DEVIATION 10.7 |
| Region of Enrollment United States | 26 participants | 31 participants | 57 participants |
| Sex: Female, Male Female | 5 Participants | 9 Participants | 14 Participants |
| Sex: Female, Male Male | 21 Participants | 22 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 31 | 12 / 26 |
| serious Total, serious adverse events | 8 / 31 | 2 / 26 |
Outcome results
Primary
CRT Responder Rate
Patients underwent baseline NYHA class and 6-minute hall walk distance (6-MHWD) assessment. After device implantation AV delays were optimized and all patients were programmed to simultaneous biventricular (BiV) pacing. At the 3-month follow-up, the NYHA class and 6-MHWD were reassessed. Non-responders were randomized 1:1 to either sequential BiV pacing with VV optimization or simultaneous BiV pacing. The responder rate at 6 months post randomization was compared between the two groups. Which is why the numbers are broken further down in the Outcome Measure table.
Time frame: 6 months
Population: Per protocol analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Simultaneous Pacing V-V Timing | CRT Responder Rate | Responders | 16 participants |
| Simultaneous Pacing V-V Timing | CRT Responder Rate | Non-Responders | 17 participants |
| Sequential VV Pacing | CRT Responder Rate | Responders | 20 participants |
| Sequential VV Pacing | CRT Responder Rate | Non-Responders | 6 participants |
Secondary
6 Minute Hall Walk Distance Test (6-MHWD)
Patients were considered non-responders if the 6-MHWD had not improved by greater than or equal to 10% compared to baseline. This statement is accurate and appropriate.
Time frame: 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Simultaneous Pacing V-V Timing | 6 Minute Hall Walk Distance Test (6-MHWD) | Responder | 10 participants |
| Simultaneous Pacing V-V Timing | 6 Minute Hall Walk Distance Test (6-MHWD) | Non-Responder | 20 participants |
| Sequential VV Pacing | 6 Minute Hall Walk Distance Test (6-MHWD) | Responder | 13 participants |
| Sequential VV Pacing | 6 Minute Hall Walk Distance Test (6-MHWD) | Non-Responder | 13 participants |
Secondary
Left Ventricular Ejection Fraction (LVEF)
Ejection fraction is a measurement of the percentage of blood leaving your heart each time it contracts. The left ventricle is the heart's main pumping chamber, so ejection fraction is usually measured only in the left ventricle (LV).
Time frame: Randomization and 9 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Simultaneous Pacing V-V Timing | Left Ventricular Ejection Fraction (LVEF) | Randomization | 30.6 percentage | Standard Deviation 10.5 |
| Simultaneous Pacing V-V Timing | Left Ventricular Ejection Fraction (LVEF) | 9 Month Follow-up Visit | 32.6 percentage | Standard Deviation 11.8 |
| Sequential VV Pacing | Left Ventricular Ejection Fraction (LVEF) | Randomization | 30.7 percentage | Standard Deviation 10.5 |
| Sequential VV Pacing | Left Ventricular Ejection Fraction (LVEF) | 9 Month Follow-up Visit | 32.1 percentage | Standard Deviation 11.6 |
Secondary
NYHA Class Progression
New York Heart Association (NYHA) functional classification provides a way of classifying the extent of heart failure. It places patients in one of four categories based on how much they are limited during physical activity; the limitations/symptoms are in regard to normal breathing and varying degrees in shortness of breath and/or angina pain.
Time frame: 6 months
Population: Per protocol analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Simultaneous Pacing V-V Timing | NYHA Class Progression | NYHA Class Improved by more than 1 category | 1 participants |
| Simultaneous Pacing V-V Timing | NYHA Class Progression | NYYHA Class Improved by 1 category | 11 participants |
| Simultaneous Pacing V-V Timing | NYHA Class Progression | NYHA Class Unchanged | 17 participants |
| Simultaneous Pacing V-V Timing | NYHA Class Progression | NYHA Class Worsened | 1 participants |
| Sequential VV Pacing | NYHA Class Progression | NYHA Class Unchanged | 7 participants |
| Sequential VV Pacing | NYHA Class Progression | NYHA Class Improved by more than 1 category | 1 participants |
| Sequential VV Pacing | NYHA Class Progression | NYHA Class Worsened | 1 participants |
| Sequential VV Pacing | NYHA Class Progression | NYYHA Class Improved by 1 category | 17 participants |