A Clinical Trial to Evaluate the HeartWare™ Ventricular Assist System (ENDURANCE SUPPLEMENTAL TRIAL)

NCT ID: NCT01966458

Last Updated: 2020-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 494 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2020-08-31

Brief Summary

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. Subjects have chronic Stage D or NYHA Class IIIB/IV left ventricular failure who have received and failed optimal medical therapy, and who are ineligible for cardiac transplantation.

Detailed Description

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.

Conditions

Chronic Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HeartWare® VAS (HVAD)

Implant of HeartWare® Ventricular Assist System

Group Type: EXPERIMENTAL

HeartWare® VAS (HVAD)

Intervention Type: DEVICE

The HeartWare® VAS is an implantable centrifugal pump that was designed to provide flows up to 10 L/min in a small device that is both lightweight and simple to use.

Control LVAD

Implant of FDA-approved LVAD approved for destination therapy

Group Type: ACTIVE_COMPARATOR

Control LVAD

Intervention Type: DEVICE

Any FDA-approved LVAD for destination therapy.

Interventions

HeartWare® VAS (HVAD)

The HeartWare® VAS is an implantable centrifugal pump that was designed to provide flows up to 10 L/min in a small device that is both lightweight and simple to use.

Intervention Type: DEVICE

Control LVAD

Any FDA-approved LVAD for destination therapy.

Intervention Type: DEVICE

Eligibility Criteria

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 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® 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 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 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medtronic Cardiac Rhythm and Heart Failure

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francis Pagani, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan Hospital

Joseph Rogers, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

The University of Alabama at Birmingham

Birmingham, Alabama, United States

Mayo Clinic (Arizona)

Phoenix, Arizona, United States

The University of Southern California

Los Angeles, California, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

Stanford University School of Medicine

Stanford, California, United States

Washington Hospital Center

Washington D.C., District of Columbia, United States

University of Florida Gainesville

Gainesville, Florida, United States

University of Miami / Jackson Memorial Hospital

Miami, Florida, United States

Tampa Transplant Institute/Tampa General Hospital

Tampa, Florida, United States

The Emory Clinic Inc.

Atlanta, Georgia, United States

Saint Joseph Hospital of Atlanta

Atlanta, Georgia, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Advocate Christ Medical Center

Oak Lawn, Illinois, United States

IU Health Methodist

Indianapolis, Indiana, United States

St. Vincent Health

Indianapolis, Indiana, United States

Jewish Hospital

Louisville, Kentucky, United States

John Ochsner Heart & Vascular Institute

New Orleans, Louisiana, United States

University of Maryland

Baltimore, Maryland, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Tufts Medical Center

Boston, Massachusetts, United States

University of Michigan Hospital

Ann Arbor, Michigan, United States

Henry Ford Hospital

Detroit, Michigan, United States

Abbott Northwestern

Minneapolis, Minnesota, United States

Mayo Clinic / St. Marys Hospital

Rochester, Minnesota, United States

Washington University / Barnes Jewish Hospital

St Louis, Missouri, United States

New York Presbyterian Hospital/Columbia

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Cleveland Clinic Foundatiojn

Cleveland, Ohio, United States

Ohio State University Medical Center

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

UPMC Presbyterian

Pittsburgh, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Baylor University Medical Center

Dallas, Texas, United States

UT Southwestern Medical Center at Dallas

Dallas, Texas, United States

Texas Heart Institute

Houston, Texas, United States

The Methodist Hospital

Houston, Texas, United States

Intermountain Medical Center

Murray, Utah, United States

University of Utah

Salt Lake City, Utah, United States

Inova Fairfax Hospital

Falls Church, Virginia, United States

Sentara Norfolk

Norfolk, Virginia, United States

University of Washington Medical Center

Seattle, Washington, United States

Northwest Cardiothoracic &Transplant Surgeons

Spokane, Washington, United States

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Countries

United States

References

Mahr C, McGee E Jr, Cheung A, Mokadam NA, Strueber M, Slaughter MS, Danter MR, Levy WC, Cheng RK, Beckman JA, May DM, Ismyrloglou E, Tsintzos SI, Silvestry SC. Cost-Effectiveness of Thoracotomy Approach for the Implantation of a Centrifugal Left Ventricular Assist Device. ASAIO J. 2020 Aug;66(8):855-861. doi: 10.1097/MAT.0000000000001209.

Reference Type: DERIVED

PMID: 32740343 (View on PubMed)

Silvestry SC, Mahr C, Slaughter MS, Levy WC, Cheng RK, May DM, Ismyrloglou E, Tsintzos SI, Tuttle E, Cook K, Birk E, Gomes A, Graham S, Cotts WG. Cost-Effectiveness of a Small Intrapericardial Centrifugal Left Ventricular Assist Device. ASAIO J. 2020 Aug;66(8):862-870. doi: 10.1097/MAT.0000000000001211.

Reference Type: DERIVED

PMID: 32740129 (View on PubMed)

Milano CA, Rogers JG, Tatooles AJ, Bhat G, Slaughter MS, Birks EJ, Mokadam NA, Mahr C, Miller JS, Markham DW, Jeevanandam V, Uriel N, Aaronson KD, Vassiliades TA, Pagani FD; ENDURANCE Investigators. HVAD: The ENDURANCE Supplemental Trial. JACC Heart Fail. 2018 Sep;6(9):792-802. doi: 10.1016/j.jchf.2018.05.012. Epub 2018 Jul 11.

Reference Type: DERIVED

PMID: 30007559 (View on PubMed)

Other Identifiers

HW004-A

Identifier Type: -

Identifier Source: org_study_id