NYHA Class III Heart Failure, NYHA Class IV Heart Failure
Conditions
Keywords
Heart Failure, Congestive Heart Failure, Chronic heart disease, Cardiac contractility modulation, CCM, CHF
Brief summary
The objective of this investigation is to evaluate the safety and effectiveness of the OPTIMIZER® System in subjects with medically refractory moderate-to-severe heart failure.
Detailed description
The Impulse Dynamics FIX-HF-5C Study is a prospective, multicenter, randomized study to evaluate the safety and efficacy of cardiac contractility modulation (CCM) signals delivered by the implantable OPTIMIZER System in patients with NYHA class III and IV heart failure and an ejection fraction 25-45%. The study will involve the recruitment of 160 subjects at a total of up to 60 sites. Those subjects who fulfill all inclusion and exclusion criteria based upon baseline test results will be randomly assigned in a 1:1 ratio to either the OPTIMIZER System plus optimal medical therapy (OMT) or to a control group receiving OMT alone. All randomized subjects will be followed for 24 weeks and shall receive the same study related assessments throughout the course of the study. In addition, all subjects will continue to receive OMT for the treatment of their heart failure. Mortality will be reported out to 2 years.
Interventions
DEVICEOptimizer System
The OPTIMIZER System delivers non-excitatory cardiac contractility modulating (CCM) electrical signals to the heart muscle. Treatment group subjects receive five non-contiguous one-hour periods of CCM signals per day.
OTHERNo intervention: Optimal medical therapy
The control group receives optimal medical therapy only.
Sponsors
Impulse Dynamics
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
1. Subjects who are 18 years of age or older 2. Subjects who are either male or female. Females of childbearing potential must be using a medically approved method of birth control and must agree to continue to use birth control throughout the study, or must be surgically sterilized (tubal ligation, hysterectomy) or post-menopausal for at least 1 year. 3. Condition 1. Subjects who have a baseline ejection fraction greater than or equal to 25% and less than or equal to 45% by echocardiography determined by the echocardiography core laboratory. 2. Subjects who have been treated for heart failure for at least 90 days (including treatment with a β-blocker for at least 90 days unless the subject is intolerant) and are in New York Heart Association functional Class III and IV at the time of enrollment. 3. Subjects receiving appropriate, stable medical therapy during the 30 days prior to enrollment for treatment of heart failure according to the region- specific guideline recommendations. For patients with EF≤35%, this regimen shall consist of the appropriate doses of diuretics, ACE-inhibitor or angiotensin II receptor blocker and β-blocker. Stable is defined as no more than a 100% increase or 50% decrease in dose. 4. Subjects who, in the opinion of the Principal Investigator (based on the current guidelines for clinical practice ), have a clinical indication for an implanted cardiac defibrillator (ICD, e.g., EF≤35%) and/or pacemaker, must have an existing device or agree to undergo implantation of such a device unless the patient refuses to undergo the implantation of such device for personal reasons. 5. Subjects who are willing and able to return for all follow-up visits.
Exclusion criteria
1. Subjects whose baseline peak VO2 is \<9 or \>20 ml O2/min/kg. 2. Subjects who have a potentially correctible cause of heart failure, such as valvular heart disease or congenital heart disease. 3. Subjects who have clinically significant angina pectoris, consisting of angina during daily life (i.e., Canadian Cardiovascular Society Angina score of II or more), an episode of unstable angina within 30 days of enrollment, or angina and/or ECG changes during exercise testing performed during baseline evaluation. 4. Subjects who have been hospitalized for heart failure which required the use of inotropic support within 30 days of enrollment. 5. Subjects who have a clinically significant amount of ambient ectopy, defined as more than 8,900 PVCs per 24 hours on baseline Holter monitoring. 6. Subjects having a PR interval greater than 375 ms. 7. Subjects who have chronic (permanent or persistent) atrial fibrillation or atrial flutter or those cardioverted within 30 days of enrollment. 8. Subjects whose exercise tolerance is limited by a condition other than heart failure (e.g., angina, COPD, peripheral vascular disease, orthopedic or rheumatologic conditions) or who are unable to perform baseline stress testing. 9. Subjects who are scheduled for a CABG or a PTCA procedure, or who have undergone a CABG procedure within 90 days or a PTCA procedure within 30 days of enrollment. 10. Subjects who have a biventricular pacing system, an accepted indication for such a device, or a QRS width of 130ms or greater. 11. Subjects who have had a myocardial infarction within 90 days of enrollment. 12. Subjects who have mechanical tricuspid valve. 13. Subjects who have a prior heart transplant. 14. Subjects on dialysis. 15. Subjects who are participating in another experimental protocol. 16. Subjects who are unable to provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak VO2 | 24 weeks | Exercise tolerance quantified by peak VO2 measured with cardiopulmonary exercise stress testing (CPX) and evaluated by a blinded core lab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minnesota Living With Heart Failure (MLWHF) Questionnaire | 24 weeks | Change in quality of life at 24 weeks compared to baseline, as assessed by the Minnesota Living with Heart Failure (MLWHF) Questionnaire. The MLWHFQ score could range from 0 to 105, with higher scores indicating more significant impairment in health-related quality of lif |
| Peak VO2 With Respiratory Exchange Ratio (RER) | 24 weeks | Peak VO2 with change in respiratory exchange ratio (RER) included as a covariate, as measured by a blinded core lab. |
| NYHA | 24 weeks | Heart failure class, as assessed by the New York Heart Association (NYHA) classification. |
| Peak VO2 With a Peak RER of ≥1.05 | 24 weeks | Peak VO2 in an analysis that only includes tests with a peak RER of ≥1.05. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 6 Minute Hall Walk | 24 weeks | Distance walked in 6 minutes |
| VE/VCO2 | 24 weeks | VE/VCO2 measured during cardiopulmonary stress testing (CPX) and evaluated by a blinded core lab. |
Countries
Czechia, Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment The treatment group receives the OPTIMIZER System implant and continues with optimal heart failure medical therapy.
Optimizer System: The OPTIMIZER System delivers non-excitatory cardiac contractility modulating (CCM) electrical signals to the heart muscle. Treatment group subjects receive five non-contiguous one-hour periods of CCM signals per day. | 74 |
| Control The Control group will not receive the OPTIMIZER System and will continue with optimal heart failure medical therapy.
No intervention: Optimal medical therapy: The control group receives optimal medical therapy only. | 86 |
| Total | 160 |
Baseline characteristics
| Characteristic | Treatment | Total | Control |
|---|---|---|---|
| 6 Minute Hall Walk (meters) | 324.07 meters STANDARD_DEVIATION 89.71 | 320.46 meters STANDARD_DEVIATION 0.94045 | 316.85 meters STANDARD_DEVIATION 88.37 |
| Age, Continuous | 61.4 years | 60.7 years | 60.0 years |
| Minnesota Living with Heart Failure Questionnaire (MLWHFQ) score | 57.35 Score on a scale STANDARD_DEVIATION 23.36 | 56.885 Score on a scale STANDARD_DEVIATION 0.28991 | 56.42 Score on a scale STANDARD_DEVIATION 22.95 |
| NYHA Class III | 64 Participants | 142 Participants | 78 Participants |
| NYHA Class IV | 10 Participants | 18 Participants | 8 Participants |
| Peak VO2 (ml/kg/min) | 15.36 ml/kg/min STANDARD_DEVIATION 2.81 | 15.425 ml/kg/min STANDARD_DEVIATION 0.141 | 15.49 ml/kg/min STANDARD_DEVIATION 2.61 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 29 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 11 Participants | 7 Participants |
| Race (NIH/OMB) White | 55 Participants | 116 Participants | 61 Participants |
| Region of Enrollment Czechia | 1 Participants | 4 Participants | 3 Participants |
| Region of Enrollment Germany | 11 Participants | 20 Participants | 9 Participants |
| Region of Enrollment United States | 62 Participants | 136 Participants | 74 Participants |
| Sex: Female, Male Female | 22 Participants | 38 Participants | 16 Participants |
| Sex: Female, Male Male | 52 Participants | 122 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 74 | 4 / 86 |
| other Total, other adverse events | 35 / 74 | 36 / 86 |
| serious Total, serious adverse events | 20 / 74 | 19 / 86 |
Outcome results
Primary
Peak VO2
Exercise tolerance quantified by peak VO2 measured with cardiopulmonary exercise stress testing (CPX) and evaluated by a blinded core lab.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Peak VO2 | 15.28 ml/kg/min | Standard Deviation 3.66 |
| Control | Peak VO2 | 14.79 ml/kg/min | Standard Deviation 3.54 |
Comparison: The FIX-HF-5C Study was a study designed to confirm the preliminary evidence reported in the FIX-HF-5 subgroup analysis demonstrating improvement in subjects with LVEF 25-45% and NYHA class III-IV. A Bayesian statistical approach was employed to leverage the data available, particularly the pVO2 results, from the FIX-HF-5 subgroup.p-value: 0.975Bayesian posterior probability
Secondary
Minnesota Living With Heart Failure (MLWHF) Questionnaire
Change in quality of life at 24 weeks compared to baseline, as assessed by the Minnesota Living with Heart Failure (MLWHF) Questionnaire. The MLWHFQ score could range from 0 to 105, with higher scores indicating more significant impairment in health-related quality of lif
Time frame: 24 weeks
Population: Randomized subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Minnesota Living With Heart Failure (MLWHF) Questionnaire | 35.26 score on a scale | Standard Deviation 24.63 |
| Control | Minnesota Living With Heart Failure (MLWHF) Questionnaire | 47.47 score on a scale | Standard Deviation 25.65 |
Secondary
NYHA
Heart failure class, as assessed by the New York Heart Association (NYHA) classification.
Time frame: 24 weeks
Population: Improvement of 1 NYHA class or more.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | NYHA | 57 Participants |
| Control | NYHA | 32 Participants |
Secondary
Peak VO2 With a Peak RER of ≥1.05
Peak VO2 in an analysis that only includes tests with a peak RER of ≥1.05.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Peak VO2 With a Peak RER of ≥1.05 | 1.13 ml/kg/min | Standard Deviation 0.96 |
| Control | Peak VO2 With a Peak RER of ≥1.05 | 1.1 ml/kg/min | Standard Deviation 0.96 |
Secondary
Peak VO2 With Respiratory Exchange Ratio (RER)
Peak VO2 with change in respiratory exchange ratio (RER) included as a covariate, as measured by a blinded core lab.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Peak VO2 With Respiratory Exchange Ratio (RER) | 15.55 ml/kg/min | Standard Deviation 3.51 |
| Control | Peak VO2 With Respiratory Exchange Ratio (RER) | 15.25 ml/kg/min | Standard Deviation 3.21 |
Other Pre-specified
6 Minute Hall Walk
Distance walked in 6 minutes
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | 6 Minute Hall Walk | 324 meters | Standard Deviation 90 |
| Control | 6 Minute Hall Walk | 317 meters | Standard Deviation 88 |
Other Pre-specified
VE/VCO2
VE/VCO2 measured during cardiopulmonary stress testing (CPX) and evaluated by a blinded core lab.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | VE/VCO2 | 15.0 unitless | Standard Deviation 9 |
| Control | VE/VCO2 | 14.7 unitless | Standard Deviation 6 |