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

Swedish Evaluation of Left Ventricular Assist Device

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.

Study Overview

• Status: Recruiting
• Conditions: End-stage Heart Failure
• Intervention / Treatment: Device: HM III; Other: OMM, optimal medical management

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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Göran Dellgren, MD; Phone Number: +4631-342 88 63; Email: goran.dellgren@vgregion.se

Study Locations

• Sweden
  • Gothenburg, Sweden, 41234
    • Recruiting
    • Sahlgrenska Univesitetssjukhustet, Transplantationscentrum
    • Contact: Göran Dellgren; Phone Number: +46 31-342 88 63; Email: goran.dellgren@vgregion.se
  • Linköping, Sweden
    • Recruiting
    • Linköping Univ Hospital
    • Contact: Peter Wodlin, MD
  • Lund, Sweden
    • Recruiting
    • Skåne University Hospital
    • Contact: Oscar Braun, MD
  • Stockholm, Sweden
    • Recruiting
    • Karolinska Univ Hospital
    • Contact: Lars Lund, MD
  • Umeå, Sweden
    • Recruiting
    • Univ Hospital of Umeå
    • Contact: Krister Lindmark, MD
  • Uppsala, Sweden
    • Recruiting
    • Uppsala Univ Hospital
    • Contact: Ola Vedin, MD
  • Örebro, Sweden
    • Recruiting
    • Örebro Univ Hospital
    • Contact: Barna Szado, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HM III; Patients randomized to mechanical circulatory support will be treated with the HeartMate III (HM III) left ventricular assist device system.	Device: HM III; Other Names: left ventrical assist device, LVAD
Active Comparator: OMM, Optimal Medical Management; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vastra Gotaland Region
• Collaborators: Karolinska University Hospital; University Hospital, Linkoeping; Skane University Hospital; University Hospital, Umeå; Region Örebro County; Uppsala University Hospital
• Investigators: Principal Investigator: Kristjan Karason, MD, Vastra Gotaland Region

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: October 23, 2015
• First Submitted That Met QC Criteria: October 28, 2015
• First Posted (Estimate): October 30, 2015

Study Record Updates

• Last Update Posted (Actual): April 26, 2023
• Last Update Submitted That Met QC Criteria: April 25, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: survival; LVAD; HM III
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: ver 6.0; 635-14 (Other Identifier: Sweden: Regional Ethical Review Board)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We have not yet made an exact plan but see no reason for not sharing the data regarding IPD underlying the results of the study, as well as the protocol, SAP and ICF after publication, but will also depend on requirement by the journal upon publication.
• IPD Sharing Time Frame: After publication
• IPD Sharing Access Criteria: Not decided yet
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF