Swedish Evaluation of Left Ventricular Assist Device as Permanent Treatment in End-stage Heart Failure

Study Overview
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Brief Summary
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The study is a prospective, randomized, non-blinded, national, multi-center study. The study will consist of the assignment of eligible patients to treatment with either a HeartMate III (HM III) left ventricular assist device system or to pharmacological treatment (optimal medical management, OMM) according to current guidelines. Eighty (80) patients will be enrolled in this study and randomized in a 1:1 fashion between the HM III and OMM, based on a modified power calculation.

Detailed Description
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The primary objective is to compare survival between left Ventricular Assist Device (LVAD) destination therapy and optimal medical management in a Swedish end stage heart failure population ineligible for cardiac transplantation. The secondary objective is to compare treatment groups with respect to organ function, functional capacity, quality of life and adverse events. All patients enrolled in the study will be followed through 2 years. Patients who continue to be on going with the HM III or on OMM past 2 years will continue be followed for their outcomes and adverse events for up to 5 years. Patient recruitment was expected to occur over 24 months, but due to difficulties in recruiting patients will be longer (approximately 48 months) The study will be conducted in Sweden at all 7 University Hospitals and implantations will be performed in 5 sites.

Official Title
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Swedish Evaluation of Left Ventricular Assist Device

Conditions
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End-stage Heart Failure

Intervention / Treatment
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* Device: HM III
* Other: OMM, optimal medical management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Adult (≥ 18 years) Chronic heart failure ≥ 45 days or stable not supported by mechanical circulatory support since >7days on single inotrope. Left ventricular ejection fraction ≤ 30%. NYHA IIIB-IV, INTERMACS profile 2-6 At least 2 of 4 adverse prognostic criteria: SHFM estimated 1-year survival ≤75% NTproBNP ≥ 2000 ng/l VO2 max < 14 ml/kg/min or <50% of predicted VO2max with attainment of anaerobic threshold (AT), or unable to perform. Need for continuous or intermittent inotropic support or >2 hospitalizations during last 6 months. Receiving medical management with optimal doses of betablockers, ACE-inhibitors or ARBs, and MRAs for at least 30 days if tolerated. Receiving CRT if indicated for at least 45 days. Receiving ICD if indicated and appropriate. Ineligible for cardiac transplantation (e.g. high age and/or co-morbidities) Considered suitable for the study by a multidisciplinary board Exclusion Criteria: Eligible for heart transplantation or is likely to become eligible after VAD treatment (bridge-to-candidacy) Indication for revascularisation, valvular surgery or other cardiac intervention expected to improve cardiac function and prognosis (CABG, PCI TAVI, mitraclip etc.) INTERMACS profile 1 crash and burn On-going mechanical circulatory support. Heart failure due to restrictive cardiomyopathy pericardial disease, active myocarditis or uncorrected thyroid disease. Mechanical aortic valve that will not be converted to a bioprosthesis or patch Moderate to severe aortic insufficiency without plans for correction Technical obstacles, which pose an inordinately high surgical risk Active, uncontrolled infection 11. Stroke within 90 days or carotid artery stenosis > 80 % 12. Significant vascular disease. 13. Severe COPD or severe restrictive lung disease. 14. Intrinsic hepatic disease as defined by liver enzyme values (AST or ALT or total bilirubin) > 5 times the upper limit of normal, or INR > 2.0, which is not due to anti-coagulant therapy. 15. Intolerance to anticoagulant or antiplatelet therapies or any other operative therapy the patient will require based upon the patient's health status. 16. Platelet count < 50,000. 17. Measured GFR <20 ml/min/1.73m2 unresponsive to inotrope treatment or chronic dialysis. 18. High risk for right ventricular failure according to echocardiography and/or invasive hemodynamic measurements as judged by the investigator (>2 parameter constitute an exclusion criteria) using a combination of the: a. Severe TI b. TAPSE < 0.72 cm c. RVEDD/LVEDD > 0.72 d. CVP > 16 mm Hg e. MPAP - RAP < 10 mmHg SPAP-DPAP/CVPm >1 ok, <0.5 very bad, in between borderline f. CVP/PCWP > 0.63 g. RVSWI < 300 mm Hg x ml/m2 h. Bilirubin > 34 micromol/L 19. Body Mass Index (BMI) > 42 kg/m2. 20. Psychiatric disease, cognitive dysfunction, alcohol or drug abuse, or psychosocial issues that are likely to impair study compliance 21. Female of childbearing age with a positive pregnancy test or not willing to use adequate contraceptive precautions during the study. 22. Condition, other than heart failure, that could limit survival to less than 2 years.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HM III<br>Patients randomized to mechanical circulatory support will be treated with the HeartMate III (HM III) left ventricular assist device system. | Device: HM III<br> <br> * Other names: left ventrical assist device, LVAD;|
| Active Comparator: OMM, Optimal Medical Management<br>Patients randomized to OMM will be treated according to international guidelines. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Eur Heart J. 2012 Jul;33(14):1787-84 | Other: OMM, optimal medical management<br>* Patients randomized to OMM will be treated according to international guidelines. All patients should receive a beta blocker, an ACE-inhibitor or an Angiotension II receptor blocker, and a mineralocorticoid receptor antagonist if tolerated and at optimally titrated doses according to guidelines. Loop diuretics should also be used as needed to control fluid retention. Other drugs that may relieve symptoms and improve prognosis can be used (incl ivabradin, digoxin, hydralazine,isosorbiddinitrate, anticoagulant agents). Patients that have an indication for implantable cardioverter defibrillator (ICD) and/or cardiac resynchronization therapy (CRT) should receive such therapy. Surgical interventions that may be indicated for specific underlying or contributing causes of heart failure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at two years of follow-up | survival | 2 years, | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants free from disabling stroke during the 2-year follow-up period | Survival free from disabling stroke (Modified Rankin Scale (MRS) >3) | 2 years | 
| A composite endpoint of survival free from disabling stroke, survival and non-planned hospitalizations | Survival free from a composite endpoint of disabling stroke, survival and non-planned hospitalizations | 2 years | 
| Survival at year of follow-up | Survival at year | 1 year | 
| Functional capacity (NYHA) during the 2-year follow-up period | functional capacity determined by NYHA classification | 2 years | 
| Functional capacity (6 min walk-test) during the 2-year follow-up period | functional capacity determined by 6 min walk-test | 2 years | 
| Functional capacity (peak VO2) | functional capacity determined by peak VO2 | 2 years | 
| Health-related quality of Life during the 2-year follow-up period | Health-related quality of Life asses with EQ-5D-5L, SF-36 and KCCQ | 2 years | 
| Number of participants with heart-failure related events |  | 2 years | 
| Cost-effectiveness during the 2-year follow-up period | Cost effectiveness calculated with QUALY (Quality-adjusted Life-year) and LY (Life year) | 2 years | 
| Renal function during the 2-year follow-up period | Glomerular filtration rate evaluated by 51 chrome-EDTA or Iohexol clearance | 2 years | 
| Hospital admissions during the 2-year follow-up period | Number of hospital admissions | 2 years | 
| Number of participants with serious adverse events (SAEs) |  | 2 years | 
| Functional capacity (peak VO2) | functional capacity determined by peak VO2 | 1 year | 
| Three-years survival | survival | 3 years | 
| Four-years survival | survival | 4 years | 
| Five-years survival | survival | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HM III, survival, LVAD