HeartWare VAD for DT Therapy - ENDURANCE Supplemental Trial

Principal Investigator: Craig Selzman
Keywords: Heart Failure , LVAD , Heart Transplant Department: Cardiothoracic Division
IRB Number: 00069093 Co Investigator: Stavros Drakos
Specialty: Cardiology, Cardiothoracic Surgery, Cardiothoracic Surgery, Cardiology, Cardiothoracic Surgery
Sub Specialties: Heart Failure, Cardiac Mechanical Support, Heart Failure, Heart Transplant, Heart Transplant
Recruitment Status: Active, not recruiting

Contact Information

Ashley Elmer

Brief Summary

Study Design

This is a prospective, randomized, controlled, unblinded, multi-center evaluation of safety and efficacy in patients implanted with a HeartWare® HVAD who receive improved blood pressure management. The study will evaluate non-inferiority of neurologic injury incidence in a new cohort of subjects receiving improved blood pressure management to a control group (i.e., any FDA-approved LVAD for destination therapy). Secondary endpoints include: a comparison of stroke/TIA incidence to a reference observed in the original IDE clinical trial (HW004) that did not specify improved blood pressure management; and non-inferiority of stroke-free success on the originally implanted device to the control group. Subjects will be randomized to HeartWare® HVAD or control LVAD in a 2:1 ratio. Each subject receiving the HeartWare® HVAD or control LVAD is followed to the primary and secondary endpoints at 12 months, with a subsequent follow-up period extending to 60 months post-implant.

Primary Endpoint:

The primary endpoint is a non-inferiority test comparing HVAD to Control considering the incidence at 12 months on the originally implanted device of neurologic injury, defined as an ICVA or HCVA with an MRS > 0 at 24-weeks post-stroke, or a TIA, or as a spinal cord infarction.

Strokes are those neurological events specified as an ICVA or an HCVA, and confirmed with computed tomography (CT). Spinal cord infarction events are reported in the Other adverse event category.


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 (Class IIIB or IV) who are: (patient must meet one of the following);

              a. 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

               b. In Class III or Class IV heart failure for at least 14 days, and dependent on intraaortic 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® HVAD or control LVAD

7. Patient must agree to participate in and comply with an improved blood pressure management program, including maintenance of a patient diary.

8. Female patients of childbearing potential must agree to use adequate contraceptive precautions (defined as oral contraceptives, intrauterine devices, surgical contraceptives or a combination of condom and spermicide) for the duration of the study.

9. 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 intraaortic 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 as diagnosed by ST or T wave changes on the ECG, diagnostic biomarkers, ongoing pain and hemodynamic abnormalities as described (Figure 2) in the guidelines published in ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non–ST-Elevation Myocardial Infarction;

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 as documented by computed tomography (CT) scan or nuclear scan

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) at the time of screening/randomization or right atrial pressure > 20 mmHg on multiple inotropes, or right ventricular ejection fraction (RVEF) <15% with clinical signs of severe right heart failure (e.g. lower extremity edema, ascites or pleural effusions refractory to treatment with diuretics and two inotropic drugs)

13. Active, uncontrolled infection diagnosed by a combination of clinical symptoms and laboratory testing, including but not limited to, continued positive cultures, elevated temperature and white blood cell (WBC) count, hypotension, tachycardia, generalized malaise despite appropriate antibiotic, antiviral or antifungal treatment

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 or ultrafiltration

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 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 COPD or severe restrictive lung disease (e.g. FEV1 < 50%)

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