Clinical trial NCT02592499: Swedish Evaluation of Left Ventricular Assist Device as Permanent Treatment in End-stage Heart Failure
Official title: Swedish Evaluation of Left Ventricular Assist Device
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: End-stage Heart Failure
Keywords: HM III
survival
LVAD
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
Collaborators: name: Karolinska University Hospital
name: University Hospital, Linkoeping
name: Skane University Hospital
name: Uppsala University Hospital
name: University Hospital, Umeå
name: Region Örebro County
First posted: 2015-10-30
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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

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.

Primary outcomes:
measure: Survival at two years of follow-up
timeFrame: 2 years,
Secondary outcomes:
measure: Number of participants free from disabling stroke during the 2-year follow-up period
timeFrame: 2 years
measure: A composite endpoint of "survival free from disabling stroke", survival and non-planned hospitalizations
timeFrame: 2 years
measure: Survival at year of follow-up
timeFrame: 1 year
measure: Functional capacity (NYHA) during the 2-year follow-up period
timeFrame: 2 years
measure: Functional capacity (6 min walk-test) during the 2-year follow-up period
timeFrame: 2 years
measure: Functional capacity (peak VO2)
timeFrame: 2 years
measure: Health-related quality of Life during the 2-year follow-up period
timeFrame: 2 years
measure: Number of participants with heart-failure related events
timeFrame: 2 years
measure: Cost-effectiveness during the 2-year follow-up period
timeFrame: 2 years
measure: Renal function during the 2-year follow-up period
timeFrame: 2 years
measure: Hospital admissions during the 2-year follow-up period
timeFrame: 2 years
measure: Number of participants with serious adverse events (SAEs)
timeFrame: 2 years
measure: Functional capacity (peak VO2)
timeFrame: 1 year
measure: Three-years survival
timeFrame: 3 years
measure: Four-years survival
timeFrame: 4 years
measure: Five-years survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Sahlgrenska Univesitetssjukhustet, Transplantationscentrum
city: Linköping
country: Sweden
facility: Linköping Univ Hospital
city: Lund
country: Sweden
facility: Skåne University Hospital
city: Stockholm
country: Sweden
facility: Karolinska Univ Hospital
city: Umeå
country: Sweden
facility: Univ Hospital of Umeå
city: Uppsala
country: Sweden
facility: Uppsala Univ Hospital
city: Örebro
country: Sweden
facility: Örebro Univ Hospital
Study officials:
affiliation: Vastra Gotaland Region
name: Kristjan Karason, MD
role: PRINCIPAL_INVESTIGATOR
References: