A Clinical Trial to Evaluate the HeartWare MVAD® System (MVAdvantage)

Not Applicable

• Conditions: Heart Failure
• Interventions: Device: HeartWare MVAD® System

• Registration Number: NCT01831544
• Lead Sponsor: Medtronic Cardiac Rhythm and Heart Failure

Brief Summary

This multi-center, prospective, non-randomized, single-arm trial will investigate the safety and performance of the HeartWare® Miniaturized Ventricular Assist Device (MVAD®) system over 24 months in subjects with advanced heart failure

Detailed Description

This multi-center, prospective, non-randomized, single-arm trial will investigate the safety and performance of the Miniaturized Ventricular Assist Device (MVAD®) system over 24 months in subjects with advanced heart failure. The primary endpoint is survival at 6 months presented as a simple proportion (subjects alive on the MVAD® pump divided by endpoint eligible subjects). Secondary endpoints include the incidence of bleeding, incidence of major infections (per INTERMACS definitions), time to death, incidence of all device failures and device malfunctions, Health Status improvement, and Functional status improvement. Safety measures will include the frequency and rates of adverse events, overall and for each specific event, which will be collected throughout VAD support.

Study Timeline

• Study First Submitted: 2013-04-08
• Study First Submitted QC: 2013-04-10
• Study First Posted: 2013-04-15
• Study Start: 2015-07-15
• Primary Completion: 2018-05-02
• Results First Submitted: 2020-03-24
• Results First Submitted QC: 2020-03-24
• Results First Posted: 2020-04-07
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-28
• Last Update Posted: 2021-06-10
• Study Completion: 2022-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 11

Inclusion Criteria

1. Must be ≥18 years of age at consent

2. Subjects with advanced heart failure symptoms (Class IIIB or IV) who meet one of the following):

   1. 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
   2. in Class III or Class IV heart failure for at least 14 days and dependent on intra-aortic balloon pump (IABP) and/or inotropes.

3. Left ventricular ejection fraction ≤25%.

4. Female subjects 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.

5. The subject has signed the informed consent form.

Exclusion Criteria

1. Body Mass Index (BMI) > 47.
2. Body Surface Area (BSA) < 1.0 m2.
3. Partial or full mechanical circulatory support within thirty days of implant.
4. Existence of any ongoing mechanical circulatory support (MCS) other than an intra-aortic balloon pump (IABP) or TandemHeart PTVA®.
5. Prior cardiac transplant or cardiomyoplasty.
6. History of confirmed, untreated abdominal or thoracic aortic aneurysm (diameter > 5 cm).
7. Acute myocardial infarction within 14 days of implant as diagnosed by ST or T wave changes on the electrocardiogram (ECG), diagnostic biomarkers, ongoing pain and hemodynamic abnormalities.
8. On ventilator support for > 72 hours within the four days immediately prior to implant.
9. Pulmonary embolus within three weeks of implant as documented by computed tomography (CT) scan or nuclear scan.
10. Symptomatic cerebrovascular disease, stroke within 180 days of implant or > 80% stenosis of carotid or cranial vessels in the absence of confirmed collateral circulation
11. Uncorrected moderate to severe aortic insufficiency.
12. Severe right ventricular failure as defined by the anticipated need for extracorporeal membrane oxygenation (ECMO) at the time of screening.
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, International Normalized Ratio (INR) > 2.0 or Partial Thromboplastin Time (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 subject's health status.
16. Serum creatinine > 3.0 mg/dL within 72 hours of implant or requiring dialysis.
17. Specific liver enzymes [Aspartate Aminotransferase (AST) (SGOT), and Alanine Aminotransferase (ALT) (SGPT)] > 3 times upper limit of normal within 72 hours of implant.
18. A total bilirubin > 3 mg/dL within 72 hours of implant, or biopsy proven liver cirrhosis or portal hypertension.
19. Pulmonary vascular resistance (PVR) is demonstrated to be unresponsive to pharmacological manipulation.
20. Subjects 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% predicted value).
23. Participation in any other trial involving investigational drugs or devices within 4 weeks prior to screening and last visit of the trial.
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 and breast feeding.
27. Psychiatric disease, irreversible cognitive dysfunction or psychosocial issues that are likely to impair compliance with the CIP and LVAD.
28. Subject unwilling or unable to comply with trial requirements.
29. Technical obstacles, which pose an inordinately high surgical risk, in the judgment of the investigator.
30. Employees of the investigator or trial site, with direct involvement in this trial or other trials under the direction of the investigator or trial site, as well as family members or employees of the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MVAD® Pump	HeartWare MVAD® System	Implant of HeartWare MVAD® System

Primary Outcome Measures

Name	Time	Method
Survival	Six month	Primary Endpoint: survival at 6 months presented as a simple proportion. Transplants, explants for recovery and exchanges (to a device other than the MVAD® pump) prior to 6 month follow-up will be eligible for endpoint analysis, with survival status identified at the time of procedure.

Secondary Outcome Measures

Name	Time	Method
Incidence of Major Bleeding	Six month and two years	Incidence of major bleeding, per INTERMACS definition; Note: No endpoints were reached, so this objective was not analyzed
Survival	Six month and two years	Overall Survival (Time to Death)
Health Status Change, as Measured by KCCQ and EuroQol EQ-5D-5L	Six month and two years	Health Status change, as measured by KCCQ and EuroQol EQ-5D-5L; Note: No endpoints were reached, so this objective was not analyzed
Length of Operative Time and Initial Hospital Stay	Six month and two years	Length of operative time and initial hospital stay; Note: No endpoints were reached, so this objective was not analyzed
Incidence of All Device Failures and Device Malfunctions	Six month and two years	Incidence of all device failures and device malfunctions per INTERMACS definition; Note: No endpoints were reached, so this objective was not analyzed
Incidence of Major Infection	Six month and two years	Incidence of major infection, per INTERMACS definition; Note: No endpoints were reached, so this objective was not analyzed
Incidence of Neurological Dysfunction	Six month and two years	Incidence of neurological dysfunction per INTERMACS definition; Note: No endpoints were reached, so this objective was not analyzed
Functional Status Change, as Measured by NYHA and 6-minute Walk	Six month and two years	Functional status change, as measured by NYHA and 6-minute walk; Note: No endpoints were reached, so this objective was not analyzed
Frequency and Rates of Adverse Events(AEs)	Six month and two years	Frequency and rates of adverse events(AEs) throughout VAD support per INTERMACS Definition; Note: No endpoints were reached, so this objective was not analyzed
Re-Hospitalizations	Six month and two years	Re-Hospitalizations, excluding planned procedures; Note: No endpoints were reached, so this objective was not analyzed
Transplantations	Six month and two years	Transplantations; Note: No endpoints were reached, so this objective was not analyzed
Explants	Six month and two years	Explants; Note: No endpoints were reached, so this objective was not analyzed

Trial Locations

Locations (11)

The Heart and Diabetes Center NRW; 🇩🇪 Bad Oeynhausen, Germany

Medical University AKH Vienna; 🇦🇹 Vienna, Austria

German Heart Institute Berlin DHZB; 🇩🇪 Berlin, Germany

Hospitalier Pitié-Salpétrière; 🇫🇷 Paris, France

St. Vincents Hospital; 🇦🇺 Darlinghurst, Australia

Hannover Medical School MHH; 🇩🇪 Hannover, Germany

Duesseldorf University Hospital; 🇩🇪 Duesseldorf, Germany

Freeman Hospital; 🇬🇧 Newcastle upon Tyne, United Kingdom

University of Leipzig Heart Center; 🇩🇪 Leipzig, Germany

Papworth Hospital NHS Foundation; 🇬🇧 Papworth Everard, United Kingdom

Uniklinik Hamburg Eppendorf (UKE); 🇩🇪 Hamburg, Germany