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

Chronic Heart Failure Clinical Trial

— DT2  

Official title:

A Prospective, Randomized, Controlled, Unblinded, Multi-Center Clinical Trial to Evaluate the HeartWare™ Ventricular Assist Device System for Destination Therapy of Advanced Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01966458
• Other study ID #: HW004-A
• Status: Completed
• Phase: N/A
• Start date: October 2013
• Est. completion date: August 2020

Study information

• Verified date: October 2020
• Source: Medtronic Cardiac Rhythm and Heart Failure
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 494
• Est. completion date: August 2020
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure

Intervention

Device:
• 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.
• Control LVAD
Any FDA-approved LVAD for destination therapy.

Locations

Country	Name	City	State
United States	University of Michigan Hospital	Ann Arbor	Michigan
United States	Saint Joseph Hospital of Atlanta	Atlanta	Georgia
United States	The Emory Clinic Inc.	Atlanta	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	The University of Alabama at Birmingham	Birmingham	Alabama
United States	Tufts Medical Center	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic Foundatiojn	Cleveland	Ohio
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	UT Southwestern Medical Center at Dallas	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	University of Florida Gainesville	Gainesville	Florida
United States	Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Texas Heart Institute	Houston	Texas
United States	The Methodist Hospital	Houston	Texas
United States	IU Health Methodist	Indianapolis	Indiana
United States	St. Vincent Health	Indianapolis	Indiana
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	The University of Southern California	Los Angeles	California
United States	Jewish Hospital	Louisville	Kentucky
United States	University of Miami / Jackson Memorial Hospital	Miami	Florida
United States	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Abbott Northwestern	Minneapolis	Minnesota
United States	Intermountain Medical Center	Murray	Utah
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	John Ochsner Heart & Vascular Institute	New Orleans	Louisiana
United States	New York Presbyterian Hospital/Columbia	New York	New York
United States	Sentara Norfolk	Norfolk	Virginia
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	University of Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Mayo Clinic (Arizona)	Phoenix	Arizona
United States	UPMC Presbyterian	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Mayo Clinic / St. Marys Hospital	Rochester	Minnesota
United States	Washington University / Barnes Jewish Hospital	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	University of Washington Medical Center	Seattle	Washington
United States	Northwest Cardiothoracic &Transplant Surgeons	Spokane	Washington
United States	Stanford University School of Medicine	Stanford	California
United States	Tampa Transplant Institute/Tampa General Hospital	Tampa	Florida
United States	Washington Hospital Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Medtronic Cardiac Rhythm and Heart Failure

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Neurologic Injury	The primary endpoint is the percent of participants at 12 months on the originally implanted device with neurologic injury, defined as a stroke with Modified Rankin Scale (MRS) > 0 at 24-weeks post-stroke, or a transient ischemic attack (TIA), or a spinal cord infarction (SCI). The Modified Rankin Scale is scored from 0 to 6, where 0 indicates an absence of symptoms and 6 indicates death. A score of 4 or higher indicates moderately severe or greater disability.	Implant to 12 Months
Secondary	Number of HeartWare VAS Participants With Stroke/TIA	The first secondary endpoint is the number of HeartWare VAS participants with stroke/TIA at 12 months on the originally implanted device.	Implant to 12 Months
Secondary	Number of Participants With Stroke-Free Success	Success is defined as alive on the originally implanted device, electively transplanted or explanted due to subject recovery and free from disabling stroke (Modified Rankin Scale >=4).	Implant to 12 Months