Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure

Chronic Heart Failure Clinical Trial

— ADVANCE  

Official title:

Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00751972
• Other study ID #: HW003
• Status: Completed
• Phase: N/A
• Start date: August 2008
• Est. completion date: August 2013

Study information

• Verified date: May 2018
• Source: Medtronic Cardiac Rhythm and Heart Failure
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and effectiveness of the HeartWare® LVAD System in patients listed for cardiac transplantation with refractory, advanced heart failure at risk of death. The primary endpoint is survival at 180 days which is defined as alive on the originally implanted HeartWare® LVAD or transplanted or explanted for recovery. Patient must survive 60 days post-explant for recovery to be considered successful. Secondary endpoints include:

• Overall survival

• Incidence of all serious adverse events, neurocognitive status and unanticipated adverse device effects.

• Incidence of all device failures and device malfunctions

• Quality of Life improvement, as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) and EuroQoL EQ-5D

• Functional status improvement, as measured by the New York Heart Association (NYHA) and 6-minute walk

The HeartWare® LVAD System was approved by the US FDA on November 20, 2012 as a bridge to cardiac transplantation (reference PMA P100047). Patients enrolled into this study will be followed to an outcome at six months, and then patients will receive continued follow-up in a separate study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: August 2013
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Must be at least 18 years of age at enrollment.

2. Body Surface Area (BSA) greater than or equal to 1.2 m2.

3. Patient is NYHA Class IV

4. Patient listed for cardiac transplantation

5. Patient meets United Network for Organ Sharing (UNOS) Status 1A or 1B listing criteria.

6. HeartWare® LVAD implant is planned as a bridge to transplant

7. The patient or legally authorized representative has signed the informed consent form

Exclusion Criteria:

1. Existence of any ongoing mechanical circulatory support (MCS) other than an intra-aortic balloon pump (IABP)

2. Prior cardiac transplant.

3. History of confirmed, untreated abdominal or thoracic aortic aneurysm > 5 cm.

4. Cardiothoracic surgery within 30 days of enrollment.

5. 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; A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. JACC Vol. 50, No.7, 2007.

6. On ventilator support for > 72 hours within the fours days immediately prior to enrollment.

7. Pulmonary embolus within three weeks of enrollment as documented by computed tomography (CT) scan or nuclear scan.

8. Symptomatic cerebrovascular disease or a > 80% carotid stenosis.

9. Patients have moderate to severe aortic insufficiency without plans for correction during pump implantation surgery.

10. Patients with mechanical, animal or human tissue heart valves are excluded.

11. 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 HeartWare® LVAD screening/enrollment or right atrial pressure > 20 mmHg on multiple inotropes, right ventricular ejection fraction (RVEF) <15% or clinical signs including lower extremity edema, ascites or pleural effusions refractory to treatment with diuretics and two inotropic drugs.

12. 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.

13. Uncorrected thrombocytopenia or generalized coagulopathy (e.g., platelet count < 100,000, INR > 1.6 or PTT > 2.5 times control in the absence of anticoagulation therapy).

14. 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.

15. Serum creatinine greater than 3.0 times the upper limit of normal within 48 hours of study enrollment or requiring dialysis (does not include use of ultra-filtration for fluid removal).

16. All three listed liver enzymes [AST (SGOT), ALT (SGPT), or LDH] > 3 times upper limit of normal or a total bilirubin > 3 mg/dl within 24 hours of study enrollment, or biopsy proven liver cirrhosis or portal hypertension.

17. Pulmonary vascular resistance is unresponsive (fixed) to pharmacologic manipulation as demonstrated by a pulmonary artery systolic pressure exceeding 60mmHg in conjunction with any one of the three following variables:

• Pulmonary vascular resistance is greater than 5 Woods Units or

• Pulmonary vascular resistance index is greater than 6 Woods Units or

• Transpulmonary gradient exceeds 16 to 20 mmHg

18. Patients requiring aortic, mitral, tricuspid or pulmonary valve replacements (including bioprosthetic valves) or left ventricular (LV) aneurysm resections.

19. Participation in any other study involving investigational drugs or devices.

20. Severe illness, other than heart disease, which would exclude cardiac transplantation.

21. Pregnancy.

22. Patient unwilling or unable to comply with study requirements.

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure

Intervention

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

Locations

Country	Name	City	State
United States	University of Michigan Hospital	Ann Arbor	Michigan
United States	The Emory Clinic	Atlanta	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
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	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	Jewish Hospital - Rudd Heart and Lung Institute	Louisville	Kentucky
United States	University of Miami / Jackson Memorial Hospital	Miami	Florida
United States	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Intermountain Medical Center	Murray	Utah
United States	John Ochsner Heart & Vascular Institute	New Orleans	Louisiana
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic (Arizona)	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Mayo Clinic / St. Marys Hospital	Rochester	Minnesota
United States	Washington University / Barnes Jewish Hospital	Saint Louis	Missouri
United States	Sharp Memorial Hospital	San Diego	California
United States	Providence Sacred Heart Medical Center	Spokane	Washington
United States	Stanford University School of Medicine	Stanford	California
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, 

References & Publications (1)

Aaronson KD, Slaughter MS, Miller LW, McGee EC, Cotts WG, Acker MA, Jessup ML, Gregoric ID, Loyalka P, Frazier OH, Jeevanandam V, Anderson AS, Kormos RL, Teuteberg JJ, Levy WC, Naftel DC, Bittman RM, Pagani FD, Hathaway DR, Boyce SW; HeartWare Ventricular — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Primary Endpoint is Success at 180 Days Which is Defined as Alive on the Originally Implanted HeartWare® LVAD or Transplanted or Explanted for Recovery. Patient Must Survive 60 Days Post-explant for Recovery to be Considered Successful.	The primary endpoint is success at 180 days which is defined as alive on the originally implanted HeartWare® LVAD or transplanted or explanted for recovery. A patient must survive 60 days post-explant for recovery to be considered successful.	180 days
Secondary	Survival to 180 Days	All subjects will be followed for date of death until 180 days.	180 Days
Secondary	Incidence of Adverse Events, Neurocognitive Status and Unanticipated Adverse Device Effects	Adverse events are only provided for patients who received a HeartWare Ventricular Assist Device (HeartWare® VAS). Adverse events as described by INTERMACS for the contemporaneous control population were not a part of the agreement for analysis and thus not provided by INTERMACS, and so not included in the Adverse Event Module and relevant Outcome Measures for comparison.	180 Days
Secondary	Incidence of All Device Failures and Device Malfunctions	The INTERMACS event device malfunction defined a failure of the HeartWare VAS as either pump failure or non-pump failure.	180 Days
Secondary	Quality of Life Change From Baseline to 180 Days, as Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ)	KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life for patients with congestive heart failure. It is a predictive tool that tracks how patients are doing if they have weakened heart muscle due to prior heart attacks, heart valve problems, viral infections, or other causes.; The KCCQ's questions are used to calculate scores in ten domains: Physical Limitation, Symptom Stability, Frequency, Burden and Total Symptom. Social Limitation, Self-Efficacy, Quality of Life, and Clinical Summary. Overall Summary: a combined measure of all the above; For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.	Baseline and 180 Days
Secondary	Change in Distance Walked in the 6-minute Walk Test Between Baseline and 180 Days	The 6MWT is a simple test which does not require expensive equipment or advanced training for technicians. The test involves asking the patient to walk the longest distance possible in a set interval of 6 min, through a walking course (corridor) preferably 30-m long. The patient can stop or slow down at any time and then resume walking, depending on his/her degree of fatigue.; A longer distance walked is indicative of a better outcome.	Baseline and 180 Days
Secondary	Quality of Life Change From Baseline to 180 Days, as Measured by EuroQoL EQ-5D	The EQ-5D is a standardized instrument for use as a generic measure of the quality of health-related life and of health outcome.; The EuroQoL EQ-5D is a descriptive system of health-related quality of life states consisting of five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which can take one of five responses. The responses record five levels of severity (no problems/slight problems/moderate problems/severe problems/extreme problems) within a particular EQ-5D dimension.; Scores are transformed to a range of 0-100, in which higher scores reflect better health status.	Baseline and 180 Days