Clinical trial NCT00751972: Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure
Official title: Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment 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: 2008-09-12
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 180 days
Secondary outcomes:
measure: Survival to 180 Days
timeFrame: 180 Days
measure: Incidence of Adverse Events, Neurocognitive Status and Unanticipated Adverse Device Effects
timeFrame: 180 Days
measure: Incidence of All Device Failures and Device Malfunctions
timeFrame: 180 Days
measure: Quality of Life Change From Baseline to 180 Days, as Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: Baseline and 180 Days
measure: Change in Distance Walked in the 6-minute Walk Test Between Baseline and 180 Days
timeFrame: Baseline and 180 Days
measure: Quality of Life Change From Baseline to 180 Days, as Measured by EuroQoL EQ-5D
timeFrame: Baseline and 180 Days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic (Arizona)
state: Arizona
city: San Diego
country: United States
facility: Sharp Memorial Hospital
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: Atlanta
country: United States
facility: The Emory Clinic
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 - Rudd Heart and Lung Institute
state: Kentucky
city: New Orleans
country: United States
facility: John Ochsner Heart & Vascular Institute
state: Louisiana
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: University of Minnesota
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: 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: Hershey
country: United States
facility: Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
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: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: Jewish Hospital/Univ of Louisville
name: Mark Slaughter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Univ of Michigan Medical Center
name: Keith Aaronson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 Assist Device (HVAD) Bridge to Transplant ADVANCE Trial Investigators. Use of an intrapericardial, continuous-flow, centrifugal pump in patients awaiting heart transplantation. Circulation. 2012 Jun 26;125(25):3191-200. doi: 10.1161/CIRCULATIONAHA.111.058412. Epub 2012 May 22.
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: Rahman F, McEvoy JW, Ohkuma T, Marre M, Hamet P, Harrap S, Mancia G, Rodgers A, Selvin E, Williams B, Muntner P, Chalmers J, Woodward M. Effects of Blood Pressure Lowering on Clinical Outcomes According to Baseline Blood Pressure and Cardiovascular Risk in Patients With Type 2 Diabetes Mellitus. Hypertension. 2019 Jun;73(6):1291-1299. doi: 10.1161/HYPERTENSIONAHA.118.12414.
citation: Teuteberg JJ, Slaughter MS, Rogers JG, McGee EC, Pagani FD, Gordon R, Rame E, Acker M, Kormos RL, Salerno C, Schleeter TP, Goldstein DJ, Shin J, Starling RC, Wozniak T, Malik AS, Silvestry S, Ewald GA, Jorde UP, Naka Y, Birks E, Najarian KB, Hathaway DR, Aaronson KD; ADVANCE Trial Investigators. The HVAD Left Ventricular Assist Device: Risk Factors for Neurological Events and Risk Mitigation Strategies. JACC Heart Fail. 2015 Oct;3(10):818-28. doi: 10.1016/j.jchf.2015.05.011.
citation: Birks EJ, McGee EC Jr, Aaronson KD, Boyce S, Cotts WG, Najjar SS, Pagani FD, Hathaway DR, Najarian K, Jacoski MV, Slaughter MS; ADVANCE Trial Investigators. An examination of survival by sex and race in the HeartWare Ventricular Assist Device for the Treatment of Advanced Heart Failure (ADVANCE) Bridge to Transplant (BTT) and continued access protocol trials. J Heart Lung Transplant. 2015 Jun;34(6):815-24. doi: 10.1016/j.healun.2014.12.011. Epub 2014 Dec 29.
citation: Goldstein DJ, Aaronson KD, Tatooles AJ, Silvestry SC, Jeevanandam V, Gordon R, Hathaway DR, Najarian KB, Slaughter MS; ADVANCE Investigators. Gastrointestinal bleeding in recipients of the HeartWare Ventricular Assist System. JACC Heart Fail. 2015 Apr;3(4):303-13. doi: 10.1016/j.jchf.2014.11.008. Epub 2015 Mar 11.
citation: Milano C, Pagani FD, Slaughter MS, Pham DT, Hathaway DR, Jacoski MV, Najarian KB, Aaronson KD; ADVANCE Investigators. Clinical outcomes after implantation of a centrifugal flow left ventricular assist device and concurrent cardiac valve procedures. Circulation. 2014 Sep 9;130(11 Suppl 1):S3-11. doi: 10.1161/CIRCULATIONAHA.113.007911.
citation: John R, Aaronson KD, Pae WE, Acker MA, Hathaway DR, Najarian KB, Slaughter MS; HeartWare Bridge to Transplant ADVANCE Trial Investigators. Drive-line infections and sepsis in patients receiving the HVAD system as a left ventricular assist device. J Heart Lung Transplant. 2014 Oct;33(10):1066-73. doi: 10.1016/j.healun.2014.05.010. Epub 2014 Jun 4.
citation: Najjar SS, Slaughter MS, Pagani FD, Starling RC, McGee EC, Eckman P, Tatooles AJ, Moazami N, Kormos RL, Hathaway DR, Najarian KB, Bhat G, Aaronson KD, Boyce SW; HVAD Bridge to Transplant ADVANCE Trial Investigators. An analysis of pump thrombus events in patients in the HeartWare ADVANCE bridge to transplant and continued access protocol trial. J Heart Lung Transplant. 2014 Jan;33(1):23-34. doi: 10.1016/j.healun.2013.12.001. Epub 2013 Dec 12.
citation: Slaughter MS, Pagani FD, McGee EC, Birks EJ, Cotts WG, Gregoric I, Howard Frazier O, Icenogle T, Najjar SS, Boyce SW, Acker MA, John R, Hathaway DR, Najarian KB, Aaronson KD; HeartWare Bridge to Transplant ADVANCE Trial Investigators. HeartWare ventricular assist system for bridge to transplant: combined results of the bridge to transplant and continued access protocol trial. J Heart Lung Transplant. 2013 Jul;32(7):675-83. doi: 10.1016/j.healun.2013.04.004.