Clinical trial NCT01166347: The HeartWare™ Ventricular Assist System as Destination Therapy of Advanced Heart Failure: the ENDURANCE Trial
Official title: A Prospective, Randomized, Controlled, Un-blinded, Multi-Center Clinical Trial to Evaluate the HeartWare™ Ventricular Assist System (VAS) for Destination Therapy of Advanced Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Heart Failure
Lead sponsor: Medtronic Cardiac Rhythm and Heart Failure
Sponsor class: INDUSTRY
First posted: 2010-07-21
Enrollment: 451
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and effectiveness of the HeartWare Ventricular Assist System in patients with chronic Stage D/ New York Heart Association (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 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.

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 (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

Primary outcomes:
measure: Stroke-Free Survival Probability for 2 Years Post Implant
timeFrame: Implant to 2 years
Secondary outcomes:
measure: Number of Participants With Bleeding
timeFrame: Implant to two years
measure: Number of Participants With Major Infections
timeFrame: Implant to two years
measure: Overall Survival at 2 Years
timeFrame: Implant to two years
measure: Number of Participants With Device Malfunctions
timeFrame: Implant to two years
measure: Health Status Change Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: Change from baseline to 2 years
measure: Health Status Change Measured by EuroQol EQ-5D (Version 3L)
timeFrame: Change from baseline to 2 years
measure: Change in Functional Status Measured by New York Heart Association (NYHA) Class
timeFrame: Change from baseline to 2 years
measure: Change in Functional Status as Measured by 6-minute Walk
timeFrame: Change from baseline to 2 years
measure: Length of Initial Hospitalization
timeFrame: Implant to the end of the initial hospitalization
measure: Number of Participants Who Had a Re-hospitalization
timeFrame: Implant to two years
measure: Duration of Re-hospitalization
timeFrame: Implant to two years
measure: Cause of Re-hospitalization
timeFrame: Implant to two years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic Hospital - Phoenix
state: Arizona
city: Los Angeles
country: United States
facility: The University of Southern California
state: California
city: San Diego
country: United States
facility: Sharp Memorial
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Leprino
state: Colorado
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida - Gainesville
state: Florida
city: Miami
country: United States
facility: University of Miami/Jackson Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa Transplant Institute/Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: The Emory Clinic Inc.
state: Georgia
city: Atlanta
country: United States
facility: Saint Joseph Hospital of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: IU Health Methodist
state: Indiana
city: Indianapolis
country: United States
facility: Saint Vincent Health
state: Indiana
city: Louisville
country: United States
facility: Jewish Hospital
state: Kentucky
city: New Orleans
country: United States
facility: John Ochsner Heart & Vascular Institute
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: St. Mary's Hospital - Mayo
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University/Barnes-Jewish Hospital
state: Missouri
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital/Columbia
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Hershey
country: United States
facility: Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas - South Western
state: Texas
city: Houston
country: United States
facility: Texas Heart Institute
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Falls Church
country: United States
facility: Innova Heart and Vascular Institute Research - Cardiac Vascular & Thoracic Surgery Associates, PC
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Spokane
country: United States
facility: Northwest Cardiothoracic &Transplant Surgeons
state: Washington
city: Milwaukee
country: United States
facility: Saint Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: University of Michigan Hospital
name: Francis Pagani, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Joseph Rogers, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rogers JG, Pagani FD, Tatooles AJ, Bhat G, Slaughter MS, Birks EJ, Boyce SW, Najjar SS, Jeevanandam V, Anderson AS, Gregoric ID, Mallidi H, Leadley K, Aaronson KD, Frazier OH, Milano CA. Intrapericardial Left Ventricular Assist Device for Advanced Heart Failure. N Engl J Med. 2017 Feb 2;376(5):451-460. doi: 10.1056/NEJMoa1602954.
citation: 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.
citation: 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.