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

Not Applicable
Recruiting
Conditions
End-stage Heart Failure
Interventions
Device: HM III
Other: OMM, optimal medical management
Registration Number
NCT02592499
Lead Sponsor
Vastra Gotaland Region
Brief Summary

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

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
80
Inclusion Criteria
  1. Signed informed consent

  2. Adult (≥ 18 years)

  3. Chronic heart failure ≥ 45 days or stable not supported by mechanical circulatory support since >7days on single inotrope.

  4. Left ventricular ejection fraction ≤ 30%.

  5. NYHA IIIB-IV, INTERMACS profile 2-6

  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.
  7. Receiving medical management with optimal doses of betablockers, ACE-inhibitors or ARBs, and MRAs for at least 30 days if tolerated.

  8. Receiving CRT if indicated for at least 45 days.

  9. Receiving ICD if indicated and appropriate.

  10. Ineligible for cardiac transplantation (e.g. high age and/or co-morbidities)

  11. Considered suitable for the study by a multidisciplinary board

Exclusion Criteria
  1. Eligible for heart transplantation or is likely to become eligible after VAD treatment (bridge-to-candidacy)

  2. Indication for revascularisation, valvular surgery or other cardiac intervention expected to improve cardiac function and prognosis (CABG, PCI TAVI, mitraclip etc.)

  3. INTERMACS profile 1 "crash and burn"

  4. On-going mechanical circulatory support.

  5. Heart failure due to restrictive cardiomyopathy pericardial disease, active myocarditis or uncorrected thyroid disease.

  6. Mechanical aortic valve that will not be converted to a bioprosthesis or patch

  7. Moderate to severe aortic insufficiency without plans for correction

  8. Technical obstacles, which pose an inordinately high surgical risk

  9. Active, uncontrolled infection

  10. 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.

  11. Intolerance to anticoagulant or antiplatelet therapies or any other operative therapy the patient will require based upon the patient's health status.

  12. Platelet count < 50,000. 17. Measured GFR <20 ml/min/1.73m2 unresponsive to inotrope treatment or chronic dialysis.

  13. 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.

  1. Condition, other than heart failure, that could limit survival to less than 2 years.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
HM IIIHM IIIPatients randomized to mechanical circulatory support will be treated with the HeartMate III (HM III) left ventricular assist device system.
OMM, Optimal Medical ManagementOMM, optimal medical managementPatients 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
Primary Outcome Measures
NameTimeMethod
Survival at two years of follow-up2 years,

survival

Secondary Outcome Measures
NameTimeMethod
Five-years survival5 years

survival

Survival at year of follow-up1 year

Survival at year

Hospital admissions during the 2-year follow-up period2 years

Number of hospital admissions

Number of participants free from disabling stroke during the 2-year follow-up period2 years

Survival free from disabling stroke (Modified Rankin Scale (MRS) \>3)

A composite endpoint of "survival free from disabling stroke", survival and non-planned hospitalizations2 years

Survival free from a composite endpoint of disabling stroke, survival and non-planned hospitalizations

Health-related quality of Life during the 2-year follow-up period2 years

Health-related quality of Life asses with EQ-5D-5L, SF-36 and KCCQ

Number of participants with heart-failure related events2 years
Three-years survival3 years

survival

Four-years survival4 years

survival

Functional capacity (NYHA) during the 2-year follow-up period2 years

functional capacity determined by NYHA classification

Functional capacity (6 min walk-test) during the 2-year follow-up period2 years

functional capacity determined by 6 min walk-test

Functional capacity (peak VO2)1 year

functional capacity determined by peak VO2

Cost-effectiveness during the 2-year follow-up period2 years

Cost effectiveness calculated with QUALY (Quality-adjusted Life-year) and LY (Life year)

Renal function during the 2-year follow-up period2 years

Glomerular filtration rate evaluated by 51 chrome-EDTA or Iohexol clearance

Number of participants with serious adverse events (SAEs)2 years

Trial Locations

Locations (7)

Sahlgrenska Univesitetssjukhustet, Transplantationscentrum

🇸🇪

Gothenburg, Sweden

Linköping Univ Hospital

🇸🇪

Linköping, Sweden

Skåne University Hospital

🇸🇪

Lund, Sweden

Karolinska Univ Hospital

🇸🇪

Stockholm, Sweden

Uppsala Univ Hospital

🇸🇪

Uppsala, Sweden

Örebro Univ Hospital

🇸🇪

Örebro, Sweden

Univ Hospital of Umeå

🇸🇪

Umeå, Sweden

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