The HeartWare™ Ventricular Assist System as Destination Therapy of Advanced Heart Failure: the ENDURANCE Trial

Medtronic Cardiac Rhythm and Heart Failure451 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

451

Conditions

Chronic Heart Failure

Interventions

HeartWare® VASDEVICE

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 LVADDEVICE

Any FDA-approved LVAD for destination therapy.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (48)

Outcomes

Primary Outcomes

Stroke-Free Survival Probability for 2 Years Post Implant

The primary endpoint of the trial is stroke-free survival at two years, defined as alive on the originally implanted device, electively transplanted or explanted due to patient recovery and free from disabling stroke (Modified Rankin Scale \>=4). 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. Weibull model estimates of survival probability (shown as a percent of 100) are used.

Time frame: Implant to 2 years

Secondary Outcomes

Number of Participants With Bleeding

Number of participants with bleeding, per Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) definition. The event of bleeding is defined as: An episode of suspected internal or external bleeding that results in one or more of the following: 1. Death, 2. Re-operation, 3. Hospitalization, 4. Transfusion of red blood cells as follows: During first 7 days post implant * Adults (≥ 50 kg): ≥ 4U packed red blood cells (PRBC) within any 24 hour period during first 7 days post implant. After 7 days post implant * Any transfusion of packed red blood cells (PRBC) after 7 days following implant.

Time frame: Implant to two years

Number of Participants With Major Infections

Number of participants with major infections, per INTERMACS definition. A major infection is defined as: A clinical infection accompanied by pain, fever, drainage and/or leukocytosis that is treated by anti-microbial agents (non-prophylactic). A positive culture from the infected site or organ should be present unless strong clinical evidence indicates the need for treatment despite negative cultures. The general categories of infection include Localized non-device infection Percutaneous site and/or pocket infection Internal pump component, inflow or outflow tract infection Sepsis

Time frame: Implant to two years

Overall Survival at 2 Years

Data from ClinicalTrials.gov

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