The HeartWare™ Ventricular Assist System as Destination Therapy of Advanced Heart Failure: the ENDURANCE Trial

The HeartWare Ventricular Assist System (VAS) is intended for use in patients with chronic
Stage D/NYHA Class IIIB/IV left ventricular failure who have received and failed optimal
medical therapy and who are ineligible for cardiac transplantation. The ENDURANCE clinical
study is a prospective, randomized, unblinded, multi-center, non-inferiority evaluation of
the HeartWare® VAS versus a control group consisting of any FDA-approved Left Ventricular
Assist Device (LVAD) approved for destination therapy. Patients are randomized to HeartWare®
VAS or control LVAD in a 2:1 ratio. Each patient receiving the HeartWare® VAS or control LVAD
is followed to the primary endpoint at 2 years, with a subsequent follow-up period extending
to 5 years post implant.

Inclusion Criteria:

1. Must be ≥18 years of age at consent

2. Body Surface Area (BSA) ≥ 1.2 m2

3. Patients with advanced heart failure symptoms (New York Heart Association (NYHA) Class
IIIB or IV) who are: (patient must meet one of the following) 3a. On optimal medical
management, including dietary salt restriction and diuretics, for at least 45 out of
the last 60 days and are failing to respond; or 3b. In NYHA Class III or NYHA Class IV
heart failure for at least 14 days, and dependent on intra aortic balloon pump (IABP)
for 7 days and/or inotropes for at least 14 days

4. Left ventricular ejection fraction ≤ 25%

5. LVAD implant is intended as destination therapy

6. Must be able to receive either the HeartWare® VAS or control LVAD

7. Female patients of childbearing potential must agree to use adequate contraceptive
precautions for the duration of the study.

8. The patient or legally authorized representative has signed the informed consent form

Exclusion Criteria:

1. Body Mass Index (BMI) > 40

2. Existence of any ongoing mechanical circulatory support (MCS) other than an
intra-aortic balloon pump (IABP)

3. Prior cardiac transplant.

4. History of confirmed, untreated abdominal or thoracic aortic aneurysm > 5 cm.

5. Cardiothoracic surgery within 30 days of randomization.

6. Acute myocardial infarction within 14 days of implant

7. Patients eligible for cardiac transplantation

8. On ventilator support for > 72 hours within the four days immediately prior to
randomization and implant.

9. Pulmonary embolus within three weeks of randomization

10. Symptomatic cerebrovascular disease, stroke within 180 days of randomization or > 80%
stenosis of carotid or cranial vessels.

11. Uncorrected moderate to severe aortic insufficiency. Correction may include repair or
bioprosthesis at the time of implant.

12. Severe right ventricular failure as defined by the anticipated need for right
ventricular assist device (RVAD) support or extracorporeal membrane oxygenation (ECMO)
or right atrial pressure > 20 mmHg on multiple inotropes, right ventricular ejection
fraction (RVEF) <15% or clinical signs

13. Active, uncontrolled infection diagnosed by a combination of clinical symptoms and
laboratory testing.

14. Uncorrected thrombocytopenia or generalized coagulopathy (e.g., platelet count <
75,000, INR > 2.0 or PTT > 2.5 times control in the absence of anticoagulation
therapy).

15. Intolerance to anticoagulant or antiplatelet therapies or any other peri- or
postoperative therapy that the investigator may administer based upon the patient's
health status.

16. Serum creatinine > 3.0 mg/dL within 72 hours of randomization or requiring dialysis
(does not include use of ultra-filtration for fluid removal).

17. Specific liver enzymes [AST (SGOT) and ALT (SGPT)] > 3 times upper limit of normal
within 72 hours of randomization.

18. A total bilirubin > 3 mg/dl within 72 hours of randomization, or biopsy proven liver
cirrhosis or portal hypertension.

19. Pulmonary vascular resistance (PVR) is demonstrated to be unresponsive to
pharmacological manipulation and the PVR > 6 Wood units.

20. Patients with a mechanical heart valve .

21. Etiology of heart failure is due to, or associated with, uncorrected thyroid disease,
obstructive cardiomyopathy, pericardial disease, amyloidosis, active myocarditis or
restrictive cardiomyopathy

22. History of severe Chronic Obstructive Pulmonary Disease (COPD) or severe restrictive
lung disease

23. Participation in any other study involving investigational drugs or devices

24. Severe illness, other than heart disease, which would limit survival to < 3 years

25. Peripheral vascular disease with rest pain or ischemic ulcers of the extremities

26. Pregnancy

27. Patient unwilling or unable to comply with study requirements

28. Technical obstacles, which pose an inordinately high surgical risk, in the judgment of
the investigator