Clinical trial NCT01966458: A Clinical Trial to Evaluate the HeartWare™ Ventricular Assist System (ENDURANCE SUPPLEMENTAL TRIAL)
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
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: 2013-10-21
Enrollment: 494
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: 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.

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

Primary outcomes:
measure: Number of Participants With Neurologic Injury
timeFrame: Implant to 12 Months
Secondary outcomes:
measure: Number of HeartWare VAS Participants With Stroke/TIA
timeFrame: Implant to 12 Months
measure: Number of Participants With Stroke-Free Success
timeFrame: Implant to 12 Months
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 (Arizona)
state: Arizona
city: Los Angeles
country: United States
facility: The University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
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: St. 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: Baltimore
country: United States
facility: Johns Hopkins Hospital
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: Rochester
country: United States
facility: Mayo Clinic / St. Marys Hospital
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University / Barnes Jewish Hospital
state: Missouri
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 Foundatiojn
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: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center at Dallas
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: Inova Fairfax Hospital
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: Aurora St. 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: 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.
citation: 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.