Heart Failure, Congestive
Conditions
Keywords
cardiac contractility modulation, heart failure, cardiopulmonary exercise test, chronic heart disease
Brief summary
The purpose of this study is to determine whether treatment with the OPTIMIZER System is safe and effective in patients with moderate to severe heart failure symptoms.
Detailed description
IMPULSE Dynamics' FIX HF 5 US Study is a prospective, multi-center, 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/IV heart failure. The study will involve the recruitment of approximately 420 subjects at a total of up to 50 sites nationwide. Those subjects who fulfill all inclusion and exclusion criteria based upon baseline test results will be randomized to receive the OPTIMIZER™ System or to a control group. All subjects randomized will be followed for 1 year and shall receive the same study related assessments throughout the course of the study. In addition, all subjects will continue to receive optimal medical therapy for the treatment of their heart failure. The primary efficacy assessment consists of a change in exercise tolerance measured by cardiopulmonary exercise testing at baseline and 6 months. Safety variables, such as the rate and cause of hospitalizations or death, shall be collected in both groups and shall be compared at 12 months.
Interventions
DEVICEOPTIMIZER System
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
* Subjects who are 18 years of age or older * Subjects who are either male or female * Subjects who have a baseline ejection fraction of 35% or less by echocardiography. * 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 patient is intolerant) and are in New York Heart Association functional Class III or IV at the time of enrollment. * Subjects receiving appropriate, stable medical therapy during the 30 days prior to enrollment for treatment of heart failure, consisting 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. * Subjects who, in the opinion of the Principle Investigator (based on the current guidelines for clinical practice), have a clinical indication for an implanted cardiac defibrillator (ICD) 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. * Subjects who are willing and able to return for all follow-up visits.
Exclusion criteria
* Subjects whose baseline VO2,max is \<9 ml 02/min/kg. * Subjects who have a potentially correctible cause of heart failure, such as valvular heart disease or congenital heart disease. * 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 electrocardiography (ECG) changes during exercise testing performed during baseline evaluation. * Subjects who have been hospitalized for heart failure which required the use of inotropic support within 30 days of enrollment. * Subjects who have a clinically significant amount of ambient ectopy, defined as more than 8,900 premature ventricular complexes (PVCs) per 24 hours on baseline Holter monitoring. * Subjects who have chronic atrial fibrillation or chronic atrial flutter or those cardioverted within 30 days of enrollment. * Subjects whose exercise tolerance is limited by a condition other than heart failure (e.g., angina, chronic obstructive pulmonary disease \[COPD\], peripheral vascular disease, orthopedic or rheumatologic conditions) or who are unable to participate in a 6-minute walk or a cardiopulmonary stress test. * Subjects who are scheduled for a coronary artery bypass graft (CABG) or a percutaneous transluminal coronary angioplasty (PTCA) procedure, or who have undergone a CABG procedure within 90 days or a PTCA procedure within 30 days of enrollment. * Subjects who have a biventricular pacing system or who have an accepted indication for such a device. * Subjects who have had a myocardial infarction within 90 days of enrollment. * Subjects who have mechanical tricuspid or aortic valves. * Subjects who have a prior heart transplant. * Subjects who are participating in another experimental protocol. * Subjects who are unable to provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Endpoint: Ventilatory Anerobic Threshold (VAT) | 24 weeks | Number of participants with improvement in exercise tolerance at 24 weeks compared to baseline, as quantified by VO2 at ventilatory anerobic threshold (VAT) measured on cardiopulmonary exercise stress testing (CPX), and evaluated by a blinded core lab. Note: An individual subject is considered a responder if VAT increases by ≥20% at 24 weeks compared to their respective baseline value. |
| Safety Endpoint: Composite All-cause Mortality and All-cause Hospitalizations | 50-weeks | The proportion of patients experiencing a composite event of all-cause mortality and all-cause hospitalizations evaluated at 50-weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak VO2 | 24 weeks | Number of participants with improvement in peak VO2 measured on cardiopulmonary exercise stress testing (CPX), and evaluated by a blinded core lab. Note: An individual subject is considered a responder if peak VO2 increases by ≥20% at 24 weeks compared to their respective baseline value. |
| New York Heart Association (NYHA) Functional Classification | 24 weeks | Number of participants with improvement in heart failure symptoms as quantified by a blinded clinician using the New York Heart Association (NYHA) functional classification at 24 weeks compared to baseline. The NYHA Class ranges from I - IV, with a lower class indicating a better status. Note: An individual subject is considered a responder if the NYHA class decreases by ≥ 1 at 24 weeks compared to their respective baseline class. |
| Minnesota Living With Heart Failure (MLWHF) Questionnaire | 24 weeks | Number of subjects will improvement 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 life. Note: An individual subject is considered a responder if the MLWHFQ score decreases by ≥10 points at 24 weeks compared to their respective baseline score. |
| Six Minute Hall Walk (6MW) Test | 24 weeks | Number of subjects with improvement in exercise tolerance at 24 weeks compared to baseline, as assessed by the the six minute hall walk (6MW) test. Note: An individual subject is considered a responder with \>40-meter increase in distance walked at 24 weeks compared to their respective baseline distance. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Group (OMT) Optimal medical treatment (OMT). Subjects receiving appropriate, stable medical therapy during the 30 days prior to enrollment for treatment of heart failure, consisting of the appropriate doses of diuretics, ACE-inhibitor or angiotensin II receptor blocker and B-blocker. | 213 |
| Treatment (OMT + CCM) Treatment group: Subjects receiving OMT and cardiac contractility modulation therapy with the Optimizer System. | 215 |
| Total | 428 |
Baseline characteristics
| Characteristic | Control Group (OMT) | Treatment (OMT + CCM) | Total |
|---|---|---|---|
| 6 Minute Hall Walk Distance | 324 meters STANDARD_DEVIATION 92.4 | 326.4 meters STANDARD_DEVIATION 82.1 | 325.2 meters STANDARD_DEVIATION 7.28 |
| Age, Continuous | 58.6 Years STANDARD_DEVIATION 12.2 | 58.1 Years STANDARD_DEVIATION 12.8 | 58.35 Years STANDARD_DEVIATION 12.5 |
| MLWHFQ score | 57.4 Score on a scale STANDARD_DEVIATION 22.6 | 60.5 Score on a scale STANDARD_DEVIATION 23 | 58.95 Score on a scale STANDARD_DEVIATION 0.282 |
| NYHA Class III | 183 Participants | 196 Participants | 379 Participants |
| NYHA Class IV | 29 Participants | 19 Participants | 48 Participants |
| Peak VO2 | 14.71 ml/kg/min STANDARD_DEVIATION 2.92 | 14.74 ml/kg/min STANDARD_DEVIATION 3.06 | 14.725 ml/kg/min STANDARD_DEVIATION 2.99 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 45 Participants | 36 Participants | 81 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 21 Participants | 18 Participants | 39 Participants |
| Race (NIH/OMB) White | 142 Participants | 154 Participants | 296 Participants |
| Region of Enrollment United States | 213 participants | 215 participants | 428 participants |
| Sex: Female, Male Female | 62 Participants | 57 Participants | 119 Participants |
| Sex: Female, Male Male | 151 Participants | 158 Participants | 309 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 212 | 13 / 210 |
| other Total, other adverse events | 135 / 212 | 152 / 210 |
| serious Total, serious adverse events | 115 / 212 | 129 / 210 |
Outcome results
Primary
Efficacy Endpoint: Ventilatory Anerobic Threshold (VAT)
Number of participants with improvement in exercise tolerance at 24 weeks compared to baseline, as quantified by VO2 at ventilatory anerobic threshold (VAT) measured on cardiopulmonary exercise stress testing (CPX), and evaluated by a blinded core lab. Note: An individual subject is considered a responder if VAT increases by ≥20% at 24 weeks compared to their respective baseline value.
Time frame: 24 weeks
Population: Intention to treat (ITT) population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Group (OMT) | Efficacy Endpoint: Ventilatory Anerobic Threshold (VAT) | 28 Participants |
| Treatment (CCM + OMT) | Efficacy Endpoint: Ventilatory Anerobic Threshold (VAT) | 38 Participants |
p-value: 0.31Fisher Exact
Primary
Safety Endpoint: Composite All-cause Mortality and All-cause Hospitalizations
The proportion of patients experiencing a composite event of all-cause mortality and all-cause hospitalizations evaluated at 50-weeks
Time frame: 50-weeks
Population: Intention-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Group (OMT) | Safety Endpoint: Composite All-cause Mortality and All-cause Hospitalizations | 103 Participants |
| Treatment (CCM + OMT) | Safety Endpoint: Composite All-cause Mortality and All-cause Hospitalizations | 112 Participants |
p-value: 0.125Blackwelder
Secondary
Minnesota Living With Heart Failure (MLWHF) Questionnaire
Number of subjects will improvement 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 life. Note: An individual subject is considered a responder if the MLWHFQ score decreases by ≥10 points at 24 weeks compared to their respective baseline score.
Time frame: 24 weeks
Population: Completed cases
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Group (OMT) | Minnesota Living With Heart Failure (MLWHF) Questionnaire | 77 Participants |
| Treatment (CCM + OMT) | Minnesota Living With Heart Failure (MLWHF) Questionnaire | 110 Participants |
Secondary
New York Heart Association (NYHA) Functional Classification
Number of participants with improvement in heart failure symptoms as quantified by a blinded clinician using the New York Heart Association (NYHA) functional classification at 24 weeks compared to baseline. The NYHA Class ranges from I - IV, with a lower class indicating a better status. Note: An individual subject is considered a responder if the NYHA class decreases by ≥ 1 at 24 weeks compared to their respective baseline class.
Time frame: 24 weeks
Population: Completed cases
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Group (OMT) | New York Heart Association (NYHA) Functional Classification | 63 Participants |
| Treatment (CCM + OMT) | New York Heart Association (NYHA) Functional Classification | 94 Participants |
Secondary
Peak VO2
Number of participants with improvement in peak VO2 measured on cardiopulmonary exercise stress testing (CPX), and evaluated by a blinded core lab. Note: An individual subject is considered a responder if peak VO2 increases by ≥20% at 24 weeks compared to their respective baseline value.
Time frame: 24 weeks
Population: Completed cases
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Group (OMT) | Peak VO2 | 23 Participants |
| Treatment (CCM + OMT) | Peak VO2 | 31 Participants |
Secondary
Six Minute Hall Walk (6MW) Test
Number of subjects with improvement in exercise tolerance at 24 weeks compared to baseline, as assessed by the the six minute hall walk (6MW) test. Note: An individual subject is considered a responder with \>40-meter increase in distance walked at 24 weeks compared to their respective baseline distance.
Time frame: 24 weeks
Population: Completed cases
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Group (OMT) | Six Minute Hall Walk (6MW) Test | 51 Participants |
| Treatment (CCM + OMT) | Six Minute Hall Walk (6MW) Test | 65 Participants |