Heart Failure
Conditions
Keywords
Heart Failure, Implantable Cardioverter Defibrillator, Cardiac Resynchronization Therapy
Brief summary
Heart failure is a progressive disease that decreases the pumping action of the heart. This may cause a backup of fluid in the heart and may result in heart beat changes. When there are changes in the heart beat sometimes an implantable heart device is used to control the rate and rhythm of the heart beat. The purpose of the REVERSE clinical trial is to determine whether pacing in both the left and right ventricles using Cardiac Resynchronization Therapy (CRT) can help slow the progression of heart failure in people who have mild or previous symptoms and poor heart pumping function. This kind of therapy has previously been shown to reduce symptoms and improve exercise capacity in people with more advanced forms of heart failure.
Interventions
DEVICECardiac Resynchronization Therapy (CRT) Device or Implantable Cardioverter Defibrillator (ICD) with CRT
All randomized patients will be implanted with a market-released Medtronic CRT or CRT/ICD device.
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with previously symptomatic heart failure but no current symptoms (New York Heart Association (NYHA) Class I, Stage C) or subjects with mild heart failure that only sometimes interferes with daily activities (NYHA Class II) * Subjects with a QRS of 120 ms or more (The QRS interval is a measurement of how the electrical signal involved in a heart beat travels/conducts through the ventricles. A wide QRS (120 ms or more) suggests that there is a conduction problem (or block) in the ventricles). * Subjects with a left ventricular ejection fraction less than or equal to 40%. (The left ventricular ejection fraction (LVEF) is a measurement of how well the left ventricle pumps blood out to the rest of the body. The higher the LVEF the more blood the ventricle is pumping.) * Subjects with a left ventricular end diastolic dimension (LVEDD) greater than or equal to 55. (The left ventricular end diastolic dimension (LVEDD) is a measurement of heart size taken during an echocardiogram that is one indication of the health of the left ventricle.)
Exclusion criteria
* Subjects who are pacemaker dependent (heart would not beat without the help of an implanted device to pace it). * Subjects with heart failure that severely limits daily activities (NYHA Class III) or subjects with severe heart failure with symptoms while resting (NYHA Class IV). * Subjects hospitalized due to heart failure within past 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Worsened for Clinical Composite Response | 12 Months | Patients considered worsened if they died, were hospitalized with worsening heart failure (HF), crossed over to other arm, demonstrated worsening in New York Heart Association (NYHA) functional class, or reported moderately/markedly worse HF symptoms compared to before CRT implant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Left Ventricular End Systolic Volume, Indexed (LVESVi) | Baseline to 12 months | The change is LVESVi measured at 12 months minus LVESVi measured at baseline. The 12-month echocardiographic measurements were made with CRT programmed off, irespective of the treatment assignment. In CRT ON patients these measurements were recorded after a 10 minute washout period. Two core laboratories performed all echo measurements. |
Countries
Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Hungary, Ireland, Italy, Norway, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
Patients were enrolled from September 2004 through September 2006 at 73 sites located in the United States, Canada, and Europe.
Pre-assignment details
A total of 684 patients were enrolled in the study. Of these, 642 patients were attempted for cardiac resynchronization therapy (CRT) device implant. 21 were unsuccessful, leaving 621 patients successfully implanted with a CRT device. Of these 621 patients, 610 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| CRT OFF Cardiac Resynchronization Therapy (CRT) turned OFF in conjunction with optimal medical therapy | 191 |
| CRT ON Cardiac Resynchronization Therapy (CRT) turned ON in conjunction with optimal medical therapy | 419 |
| Total | 610 |
Baseline characteristics
| Characteristic | CRT ON | Total | CRT OFF |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 190 Participants | 273 Participants | 83 Participants |
| Age, Categorical Between 18 and 65 years | 229 Participants | 337 Participants | 108 Participants |
| Age Continuous | 62.9 years STANDARD_DEVIATION 10.6 | 62.5 years STANDARD_DEVIATION 11 | 61.8 years STANDARD_DEVIATION 11.6 |
| Region of Enrollment Austria | 4 participants | 6 participants | 2 participants |
| Region of Enrollment Belgium | 3 participants | 4 participants | 1 participants |
| Region of Enrollment Canada | 4 participants | 5 participants | 1 participants |
| Region of Enrollment Czech Republic | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Denmark | 46 participants | 65 participants | 19 participants |
| Region of Enrollment France | 34 participants | 49 participants | 15 participants |
| Region of Enrollment Germany | 11 participants | 17 participants | 6 participants |
| Region of Enrollment Hungary | 13 participants | 19 participants | 6 participants |
| Region of Enrollment Ireland | 4 participants | 5 participants | 1 participants |
| Region of Enrollment Italy | 12 participants | 17 participants | 5 participants |
| Region of Enrollment Netherlands | 4 participants | 6 participants | 2 participants |
| Region of Enrollment Norway | 4 participants | 7 participants | 3 participants |
| Region of Enrollment Spain | 18 participants | 27 participants | 9 participants |
| Region of Enrollment Sweden | 17 participants | 24 participants | 7 participants |
| Region of Enrollment United Kingdom | 9 participants | 15 participants | 6 participants |
| Region of Enrollment United States | 235 participants | 343 participants | 108 participants |
| Sex: Female, Male Female | 92 Participants | 131 Participants | 39 Participants |
| Sex: Female, Male Male | 327 Participants | 479 Participants | 152 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 | 61 / 119 | 140 / 491 | 2 / 38 |
| serious Total, serious adverse events | 122 / 191 | 268 / 419 | 13 / 38 |
Outcome results
Primary
Percentage of Patients Worsened for Clinical Composite Response
Patients considered worsened if they died, were hospitalized with worsening heart failure (HF), crossed over to other arm, demonstrated worsening in New York Heart Association (NYHA) functional class, or reported moderately/markedly worse HF symptoms compared to before CRT implant.
Time frame: 12 Months
Population: All randomized patients were included using Intent to Treat (ITT).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CRT OFF | Percentage of Patients Worsened for Clinical Composite Response | 21.5 Percentage of participants worsened |
| CRT ON | Percentage of Patients Worsened for Clinical Composite Response | 16 Percentage of participants worsened |
Comparison: Null hypothesis: Percentage worsened in CRT OFF group = Percentage worsened in CRT ON groupp-value: 0.1Chi-squared
Secondary
Change in Left Ventricular End Systolic Volume, Indexed (LVESVi)
The change is LVESVi measured at 12 months minus LVESVi measured at baseline. The 12-month echocardiographic measurements were made with CRT programmed off, irespective of the treatment assignment. In CRT ON patients these measurements were recorded after a 10 minute washout period. Two core laboratories performed all echo measurements.
Time frame: Baseline to 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CRT OFF | Change in Left Ventricular End Systolic Volume, Indexed (LVESVi) | -1.3 milliliters per meters squared | Standard Deviation 23.4 |
| CRT ON | Change in Left Ventricular End Systolic Volume, Indexed (LVESVi) | -18.4 milliliters per meters squared | Standard Deviation 29.5 |
Comparison: Null hypothesis: mean 12-month change in LVESVi in group 1 = mean 12-month change in LVESVi in group 2.p-value: <0.0001t-test, 2 sided