Clinical trial NCT02170363: HeartMate 3™ CE Mark Clinical Investigation Plan
Official title: HeartMate 3™ CE Mark Clinical Investigation Plan
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Advanced Refractory Left Ventricular Heart Failure
Keywords: Heart Failure
Ventricular Dysfunction
Cardiomyopathies
Heart Disease
Cardiovascular Disease
Heart-assist devices
Thoratec Corporation
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
Collaborators: name: Center for Life Sciences
name: Emergo
name: KCRI
name: Thoratec Corporation
First posted: 2014-06-23
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Survival
timeFrame: 6 months
Secondary outcomes:
measure: Quality of Life (EQ-5D-5L)
timeFrame: Baseline, Month 1, Month 3, Month 6
measure: Functional Status - Six Minute Walk Test (6MWT)
timeFrame: Baseline, Month 1, Month 3, Month 6
measure: Functional Status - New York Heart Association (NYHA) Classification
timeFrame: Baseline, Month 1, Month 3, Month 6
measure: All Adverse Events
timeFrame: As they occurred, Baseline through 180 Days
measure: Device Malfunctions
timeFrame: 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
measure: Reoperations
timeFrame: As they occurred, Baseline through 180 Days
measure: Rehospitalizations
timeFrame: As they occurred, Baseline through 180 Days
measure: Stroke Free Survival
timeFrame: 6 months
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Vienna
country: Austria
facility: AKH Medical University of Vienna
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Prague
country: Czechia
facility: Institute for Clinical and Experimental Medicine (IKEM)
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum NRW Thorax- und Kardiovaskularchirurgie Clinic
city: Berlin
country: Germany
facility: Deutsches Herzzentrum Berlin
city: Freiburg
country: Germany
facility: Universitats-Herzzentrum Freiburg
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Leipzig
country: Germany
facility: Herzentrum Leipzig GmbH
city: Astana
country: Kazakhstan
facility: National Research Center for Cardiac Surgery
Study officials:
affiliation: Abbott
name: Carlo Gazzola, B. Sc.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.