Heart Failure
Conditions
Keywords
NYHA III, NYHA IV, ACC Stage C, Heart Failure, Congestive Heart Failure, C-Pulse, Counterpulsation, Heart Assist, Sunshine Heart, Left Heart Failure
Brief summary
Sunshine Heart is sponsoring a prospective, multi-center, randomized trial to assess the safety and efficacy of the C-Pulse® System (C-Pulse). The purpose of the study is to determine whether the use of the C-Pulse as a treatment for patients in moderate to severe heart failure (HF) has demonstrated safety and efficacy, such that the C-Pulse System merits Food and Drug Administration (FDA) approval to market the device in the United States.
Detailed description
The C-Pulse® System is indicated for use in patients with moderate to severe heart failure while on optimal heart failure drug and on device therapies. The C-Pulse® System is intended to relieve the symptoms of heart failure, improve quality of life and cardiac function, and reduce the need for heart failure hospitalization. It is intended for use in hospital and at home. It is not intended as a replacement for heart function; it is not life sustaining or life-supporting therapy. It does not preclude the use of other heart failure therapies, such as valve surgery, heart transplantation or LVAD. The Sunshine Heart C-Pulse System is an implantable, non-blood contacting, non-obligatory, heart assist device. The system provides cardiac assistance through an extra-aortic balloon Cuff and ECG sense lead connected by means of a Percutaneous Interface Lead (PIL) to an external pneumatic Driver. The PIL is held secure externally, at the exit site, with a simple adhesive clip (C-Patch or similar) for immobilization of the external part of the PIL. The Driver is adjusted using a dedicated notebook computer (Programmer) with specialized software. The non-blood contacting feature of the C-Pulse® System also allows the device to be intermittently turned off as tolerated. This allows the patient freedom for personal hygiene.
Interventions
DEVICEC-Pulse® System Counterpulsation
The Sunshine Heart C-Pulse System is an implantable, non-blood contacting, non-obligatory, heart assist device. The system provides cardiac assistance through an extra-aortic balloon Cuff and ECG sense lead connected by means of a Percutaneous Interface Lead (PIL) to an external pneumatic Driver. The PIL is held secure externally, at the exit site, with a simple adhesive clip (C-Patch or similar) for immobilization of the external part of the PIL. The Driver is adjusted using a dedicated notebook computer (Programmer) with specialized software.
Sponsors
Nuwellis, Inc.
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. Left ventricular ejection fraction (LVEF) ≤ 35% (by transthoracic ECHO within 90 days prior to randomization) 2. ACC/AHA Stage C and NYHA III to ambulatory Class IV 3. Age ≥ 18 years 4. Must have cardiac resynchronization therapy (CRT) when clinically indicated, implanted ≥90 days prior to randomization. 5. Must have an implanted cardio-defibrillator (ICD) when clinically indicated, implanted at least 30 days prior to randomization. Note: If a subject is clinically indicated for an ICD but refuses the ICD, he/she may be enrolled. Please document the refusal of the ICD in the medical record and the eCRFs. 6. Patient must be on stable, up-titrated medical therapy as recommended according to current guidelines (Circulation. 2009; 119 (12): 1977-2016) which minimally includes: * ACE-inhibitor (ACE-I) at stable doses for 1 month prior to enrollment, if tolerated, AND * a beta blocker (carvedilol, sustained release metoprolol succinate, or bisoprolol) for 3 months prior to enrollment, if tolerated, with a stable up-titrated dose for 1 month prior to enrollment. * This also includes an Angiotensin II Receptor Blocker (ARB) at stable doses for 1 month prior to enrollment, if tolerated, when ACE-I is not tolerated. * Stable is defined as no more than a 100% increase or a 50% decrease in dose. If the patient is intolerant to ACE-I, ARB, or beta blockers, documented evidence must be available. * In those intolerant to both ACE-I and ARB, combination therapy with hydralazine and oral nitrate should be considered. Therapeutic equivalence for ACE-I substitutions is allowed within the enrollment stability timelines. * Aldosterone inhibitor therapy should be added. Eplerenone requires dosage stability for 1 month prior to enrollment. * Diuretics may be used as necessary to keep the patient euvolemic. 7. Functional limitation due to heart failure as defined by a 6 Minute Walk test of ≥ 175 ≤ 375 meters, measured within 30 days prior to randomization 8. At least one hospitalization for decompensated heart failure as defined below, while on heart failure medications, within 12 months prior to randomization or BNP level \> 300 or NTproBNP \> 1500 Heart failure related hospitalization is defined by the following: * signs and symptoms of worsening heart failure; and * treatment with intravenous heart failure therapy (including but not limited to diuretic or inotropic therapy) and * a minimum of one date change in the hospital 9. Patient understands the nature of the procedure and on-going device therapy, is willing to comply with associated follow-up evaluations, and provide written informed consent prior to the procedure.
Exclusion criteria
1. Any evidence, as assessed within 90 days prior to enrollment, of either: 1. Ascending aortic calcification on posterior-anterior or lateral chest x-ray 2. Calcific ascending aortic disease as detected by non-contrast CT scan 3. Ascending aorto-coronary artery bypass grafts, history of aortic dissection, Marfans disease or other connective tissue disorder or repaired aortic coarctation OR 4. Has had an ascending aortic composite graft or root replacement 2. Aorta not conforming to specified dimensional constraints defined by CT scan, most specifically mid ascending aortic outside diameter less than 28 mm or greater than 42 mm 3. Inotrope dependence - inability to wean from inotropic therapy 4. ACC/AHA Stage D heart failure or non-ambulatory NYHA Class IV subject 5. Hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, pericardial disease, amyloidosis, active myocarditis, diastolic heart failure or technically challenging congenital heart disease 6. Reversible cause of heart failure that may be remedied by conventional surgery or other intervention 7. Moderate to severe aortic insufficiency (≥ 2+) 8. ST elevation myocardial infarction (STEMI) within 30 days prior to randomization 9. Cardiac surgery within 90 days prior to randomization 10. Prior cardiac transplantation, left ventricular reduction surgery, passive restraint device or surgically implanted left ventricular assist device 11. Anticipated concomitant cardiac surgical procedure 12. Serum creatinine ≥ 2.5mg/dL or any form of dialysis within 30 days prior to randomization 13. Evidence of intrinsic hepatic disease as defined as biopsy proven liver cirrhosis; or liver enzyme values (AST, ALT or total bilirubin) that are \> 3 times the upper limit of normal within 30 days prior to randomization 14. Patient has severe intrinsic pulmonary disease in judgment of the investigator 15. Body Mass Index (BMI) \< 18 or \> 45 kg/m2 16. Suspected or active systemic infection 1. Within 14 days prior to randomization and 2. Evidenced by positive culture, antibiotics for empiric treatment or elevated WBC \> 12K and temperature \>38o C 17. Stroke or transient ischemic attack (TIA) within the 90 days prior to randomization; or \> 80% carotid stenosis as determined by carotid Doppler ultrasound within 90 days prior to randomization 18. Positive serum pregnancy test, for women of childbearing potential 19. Patient has a condition, other than heart failure, which would limit survival to less than 2 years 20. Patient is currently enrolled or has participated in the last 30 days in another therapeutic or interventional clinical study 21. Patient demonstrates compliance issues that in the opinion of the investigator could interfere with the ability to manage the therapy (i.e. uncontrolled diabetes, mental health issues, etc.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Safety Outcome | 4 Years Follow-up | The primary safety endpoint is serious procedure and device related adverse events as determined by CEC adjudication. No formal statistical hypotheses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in 6 Minute Hall Walk (6MW) at 12-months | 12-months | improvement of distance walked during the 6MW at 12-months. |
| Improvement in LVEF at 12 Months. | 12-months | Improvement in left ventricular ejection fraction (LVEF) at 12 months. |
| Improvement in KCCQ Score at 12-months. | 12-months | The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a quality-of-life assessment for heart failure patients taking into consideration severity of heart failure symptoms and limitations patients experience. The scores are scaled from 0 to 100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Participants Study participants consisted of Treatment Arm (n=17) who received the C-Pulse System and Control Arm (n=18) who received standard optimal medical therapy. | 35 |
| Total | 35 |
Baseline characteristics
| Characteristic | Study Participants |
|---|---|
| Age, Continuous Control Arm | 58.5 years STANDARD_DEVIATION 8.2 |
| Age, Continuous Treatment Arm | 63.3 years STANDARD_DEVIATION 11.7 |
| Intermacs Subject Profile/Status Control Arm 4: Resting Symptoms | 4 Participants |
| Intermacs Subject Profile/Status Control Arm 5: Exertion Intolerant | 3 Participants |
| Intermacs Subject Profile/Status Control Arm 6: Exertion Limited | 7 Participants |
| Intermacs Subject Profile/Status Control Arm 7: Advanced NYHA Class III | 1 Participants |
| Intermacs Subject Profile/Status Control Arm Not Available | 3 Participants |
| Intermacs Subject Profile/Status Treatment Arm 4: Resting Symptoms | 0 Participants |
| Intermacs Subject Profile/Status Treatment Arm 5: Exertion Intolerant | 6 Participants |
| Intermacs Subject Profile/Status Treatment Arm 6: Exertion Limited | 7 Participants |
| Intermacs Subject Profile/Status Treatment Arm 7: Advanced NYHA Class III | 3 Participants |
| Intermacs Subject Profile/Status Treatment Arm Not Available | 1 Participants |
| NYHA Classification Control Arm Class I | 0 Participants |
| NYHA Classification Control Arm Class II | 0 Participants |
| NYHA Classification Control Arm Class III | 18 Participants |
| NYHA Classification Control Arm Class IV | 0 Participants |
| NYHA Classification Treatment Arm Class I | 0 Participants |
| NYHA Classification Treatment Arm Class II | 0 Participants |
| NYHA Classification Treatment Arm Class III | 17 Participants |
| NYHA Classification Treatment Arm Class IV | 0 Participants |
| Race/Ethnicity, Customized Control Arm Black or African American | 8 Participants |
| Race/Ethnicity, Customized Control Arm Caucasian | 9 Participants |
| Race/Ethnicity, Customized Control Arm Not Disclosed | 1 Participants |
| Race/Ethnicity, Customized Treatment Arm Black or African American | 5 Participants |
| Race/Ethnicity, Customized Treatment Arm Caucasian | 9 Participants |
| Race/Ethnicity, Customized Treatment Arm Not Disclosed | 3 Participants |
| Region of Enrollment United States | 35 Participants |
| Sex: Female, Male Control Arm Female | 4 Participants |
| Sex: Female, Male Control Arm Male | 14 Participants |
| Sex: Female, Male Treatment Arm Female | 2 Participants |
| Sex: Female, Male Treatment Arm Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 10 / 19 | 5 / 19 |
| other Total, other adverse events | 9 / 19 | 1 / 19 |
| serious Total, serious adverse events | 16 / 19 | 15 / 19 |
Outcome results
Primary
Primary Safety Outcome
The primary safety endpoint is serious procedure and device related adverse events as determined by CEC adjudication. No formal statistical hypotheses.
Time frame: 4 Years Follow-up
Population: Study was closed early with only 38 randomized subjects (19 treatment group and 19 control). Primary and secondary endpoints were not statistically evaluated as there was insufficient sample size and follow-up. The primary safety outcome was only applicable to the implant treatment arm as it is specifically measuring device and/or procedure related serious adverse events (control arm was treated as standard of care and did not undergo a procedure for the study device to be placed).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Study Participants | Primary Safety Outcome | Device Related Serious Adverse Event (infection, device malfunction, worsening heart failure) | 5 Participants |
| Study Participants | Primary Safety Outcome | Procedure Related Serious Adverse Events (MI, arrhythmias, fluid collection) | 6 Participants |
Secondary
Improvement in 6 Minute Hall Walk (6MW) at 12-months
improvement of distance walked during the 6MW at 12-months.
Time frame: 12-months
Population: Number of participants that completed the 6MW
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Participants | Improvement in 6 Minute Hall Walk (6MW) at 12-months | 279 meters | Standard Deviation 164 |
| Control Group | Improvement in 6 Minute Hall Walk (6MW) at 12-months | 289 meters | Standard Deviation 95 |
Secondary
Improvement in KCCQ Score at 12-months.
The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a quality-of-life assessment for heart failure patients taking into consideration severity of heart failure symptoms and limitations patients experience. The scores are scaled from 0 to 100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent
Time frame: 12-months
Population: Number of Participants that completed the KCCQ at 12-months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Participants | Improvement in KCCQ Score at 12-months. | 61.4 score on a scale | Standard Deviation 23.1 |
| Control Group | Improvement in KCCQ Score at 12-months. | 52.3 score on a scale | Standard Deviation 22.5 |
Secondary
Improvement in LVEF at 12 Months.
Improvement in left ventricular ejection fraction (LVEF) at 12 months.
Time frame: 12-months
Population: Number of participants with LVEF at 12-months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Participants | Improvement in LVEF at 12 Months. | 22.0 percentage | Standard Deviation 2.7 |
| Control Group | Improvement in LVEF at 12 Months. | 22.0 percentage | Standard Deviation 7.6 |