C-Pulse® System: A Heart Assist Device Clinical Study

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.

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.

Eligibility Criteria:
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.)