HeartMate 3™ CE Mark Clinical Investigation Plan (HM3 CE Mark)

The purpose of this clinical investigation is to evaluate the performance and safety of the HeartMate 3 Left Ventricular Assist System (HM3 LVAS) To support obtaining CE Mark for the HM3 LVAS in Europe, a multi-center clinical study will be conducted in multiple countries. The clinical study will be conducted in compliance with the Declaration of Helsinki, ICH/GCP and EN ISO 14155:2011 Requirements for Clinical Investigations and in accordance with country-specific requirements, under one clinical study protocol.

This study will evaluate the performance of the HM3 LVAS, side effects and undesirable conditions within acceptable risks and weigh them against the intended performance of HM3 LVAS in accordance with Essential Requirements 2, 5 and 16 of the Active Implantable Medical Device Directive 90/385/EEC (AIMDD).

Study Overview

• Status: Completed
• Conditions: Advanced Refractory Left Ventricular Heart Failure
• Intervention / Treatment: Device: Left Ventricular Assist System (LVAS)

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3181
      • The Alfred Hospital
• Austria
  • Vienna, Austria, A-1090
    • AKH Medical University of Vienna
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G-2C4
      • Toronto General Hospital
• Czechia
  • Prague, Czechia, 4
    • Institute for Clinical and Experimental Medicine (IKEM)
• Germany
  • Bad Oeynhausen, Germany, 32545
    • Herz- und Diabeteszentrum NRW Thorax- und Kardiovaskularchirurgie Clinic
  • Berlin, Germany, 13353
    • Deutsches Herzzentrum Berlin
  • Freiburg, Germany, 79106
    • Universitats-Herzzentrum Freiburg
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Leipzig, Germany, 04280
    • Herzentrum Leipzig GmbH
• Kazakhstan
  • Astana, Kazakhstan, 010000
    • National Research Center for Cardiac Surgery

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patient or legal representative has signed Informed Consent Form (ICF)
2. Age ≥ 18 years
3. BSA ≥ 1.2 m2
4. NYHA IIIB or IV OR ACC/AHA Stage D
5. LVEF ≤ 25%
6. CI ≤ 2.2 L/min/m2, while not on inotropes

7. Patients must also meet one of the following:

   - On Optimal Medical Management (OMM), based on current heart failure practice guidelines for at least 45 out of the last 60 days and are failing to respond,

   OR

   - In NYHA class IIIB or IV heart failure for at least 14 days AND dependent on intraaortic balloon pump (IABP) for at least 7 days,

   OR

   - Inotrope dependent/unable to wean from inotropes

   OR

   - Listed for Transplant

8. Females of child bearing age must agree to use adequate contraception

Exclusion Criteria:

1. Etiology of HF due to or associated with uncorrected thyroid disease, obstructive cardiomyopathy, pericardial disease, amyloidosis or restrictive cardiomyopathy
2. Technical obstacles which pose an inordinately high surgical risk, in the judgment of the investigator
3. Existence of ongoing mechanical circulatory support (MCS) other than IABP
4. Positive pregnancy test if of childbearing potential
5. Lactating mothers
6. Presence of mechanical aortic cardiac valve that will not be converted to a bioprosthesis at the time of LVAD implant
7. History of any organ transplant
8. Platelet count < 100,000 x 103/L (< 100,000/ml)
9. Psychiatric disease/disorder, irreversible cognitive dysfunction or psychosocial issues that are likely to impair compliance with the study protocol and LVAS management
10. History of confirmed, untreated AAA > 5 cm in diameter
11. Presence of an active, uncontrolled infection
12. Intolerance to anticoagulant or antiplatelet therapies or any other peri/post-operative therapy the investigator will require based upon the patients' health status

13. Presence of any one of the following risk factors for indications of severe end organ dysfunction or failure:

    1. An INR ≥ 2.5 not due to anticoagulation therapy
    2. Total bilirubin > 43 umol/L (2.5 mg/dl), shock liver, or biopsy proven liver cirrhosis
    3. History of severe chronic obstructive pulmonary disease (COPD) defined by FEV1/FVC < 0.7, or FEV1 <50% predicted
    4. Fixed pulmonary hypertension with a most recent PVR ≥ 8 Wood units that is unresponsive to pharmacologic intervention
    5. History of stroke within 90 days prior to enrollment, or a history of cerebrovascular disease with significant (> 80%) carotid artery stenosis
    6. Serum creatinine ≥221umol/L (2.5 mg/dl) or the need for chronic renal replacement therapy
    7. Significant peripheral vascular disease (PVD) accompanied by rest pain or extremity ulceration
14. Patient has moderate to severe aortic insufficiency without plans for correction during pump implant
15. Pre albumin < 150 mg/L, or Albumin < 30g/L (3 g/dL)
16. Planned Bi-VAD support prior to enrollment
17. Patient has known hypo or hyper coagulable states such as disseminated intravascular coagulation and heparin induced thrombocytopenia
18. Participation in any other clinical investigation that is likely to confound study results or affect the study
19. Any condition other than HF that could limit survival to less than 24 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HeartMate 3; Left Ventricular Assist System (LVAS) to be used on Subjects with advanced refractory left ventricular heart failure	Device: Left Ventricular Assist System (LVAS); Implantation of left ventricular assist device for hemodynamic support

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Comparison of survival at 6 months of Left Ventricular Assist Device (LVAD) support to a performance goal established using matched HeartMate II INTERMACS data	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life (EQ-5D-5L)	The EQ-5D-5L is a standardized measure of health status developed by the EuroQol Group. Patients describe their perceived health status using an analog scale with 0 as the worst health the patient can imagine and 100 as the best health (Visual Analog Score). The patients' scores at one, three and six months were compared to their baseline scores and the resulting positive scores indicated improved quality of life.	Baseline, Month 1, Month 3, Month 6
Functional Status - Six Minute Walk Test (6MWT)	The Six Minute Walk Test(6MWT)measures the distance that a patient can walk in a period of 6 minutes. The distance walked is measured in meters. This test measures the patients' functional status. The more meters a patient can walk over baseline indicates improvement in functional status.	Baseline, Month 1, Month 3, Month 6
Functional Status - New York Heart Association (NYHA) Classification	NYHA classification relates symptoms to every day activities and patients quality of life. Class 1 = no limitations on physical activity Class 2 - slight limitation of physical activity Class 3 - marked limitation of physical activity Class 4 = unable to carry out any physical activity without discomfort	Baseline, Month 1, Month 3, Month 6
All Adverse Events	Frequency of pre-defined anticipated adverse events	As they occurred, Baseline through 180 Days
Device Malfunctions	Frequency and incidence of device malfunction	As they occurred, Baseline through 180 Days; Subjects that remain ongoing after 6 months will continue to be followed to 24 months post-implant or outcome
Reoperations	Frequency of reoperations	As they occurred, Baseline through 180 Days
Rehospitalizations	Frequency and incidence of rehospitalizations	As they occurred, Baseline through 180 Days
Stroke Free Survival	Percentage of participants free of debilitating stroke (Modified Rankin Score > 3)	6 months

Collaborators and Investigators

• Sponsor: Abbott Medical Devices
• Collaborators: Thoratec Corporation; KCRI; Center for Life Sciences; Emergo
• Investigators: Study Director: Carlo Gazzola, B. Sc., Abbott

Publications and helpful links

General Publications

• Netuka I, Sood P, Pya Y, Zimpfer D, Krabatsch T, Garbade J, Rao V, Morshuis M, Marasco S, Beyersdorf F, Damme L, Schmitto JD. Fully Magnetically Levitated Left Ventricular Assist System for Treating Advanced HF: A Multicenter Study. J Am Coll Cardiol. 2015 Dec 15;66(23):2579-2589. doi: 10.1016/j.jacc.2015.09.083.
• Schmitto JD, Pya Y, Zimpfer D, Krabatsch T, Garbade J, Rao V, Morshuis M, Beyersdorf F, Marasco S, Sood P, Damme L, Netuka I. Long-term evaluation of a fully magnetically levitated circulatory support device for advanced heart failure-two-year results from the HeartMate 3 CE Mark Study. Eur J Heart Fail. 2019 Jan;21(1):90-97. doi: 10.1002/ejhf.1284. Epub 2018 Jul 27.
• Krabatsch T, Netuka I, Schmitto JD, Zimpfer D, Garbade J, Rao V, Morshuis M, Beyersdorf F, Marasco S, Damme L, Pya Y. Heartmate 3 fully magnetically levitated left ventricular assist device for the treatment of advanced heart failure -1 year results from the Ce mark trial. J Cardiothorac Surg. 2017 Apr 4;12(1):23. doi: 10.1186/s13019-017-0587-3.

Helpful Links

• Manuscript: Fully Magnetically Levitated Left Ventricular Assist System for Treating Advanced HF

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): March 9, 2020

Study Registration Dates

• First Submitted: June 19, 2014
• First Submitted That Met QC Criteria: June 19, 2014
• First Posted (Estimate): June 23, 2014

Study Record Updates

• Last Update Posted (Actual): June 27, 2022
• Last Update Submitted That Met QC Criteria: June 23, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Heart Failure; Cardiovascular Disease; Heart Disease; Thoratec Corporation; Ventricular Dysfunction; Cardiomyopathies; Heart-assist devices
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: TC02212014