Clinical trial NCT02224755: MOMENTUM 3 IDE Clinical Study Protocol
Official title: Thoratec Corporation MOMENTUM 3, Multi-center Study of MagLev Technology in Patients Undergoing MCS Therapy With HeartMate 3™ IDE Clinical Study Protocol
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Advanced Refractory Left Ventricular Heart Failure
Keywords: Heart Failure
Left Ventricular Assist Device
Ventricular Dysfunction
Cardiomyopathy
Heart Disease
Cardiovascular Disease
Heart-assist devices
Thoratec Corporation
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
Collaborators: name: Thoratec Corporation
First posted: 2014-08-25
Enrollment: 1028
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the study is to evaluate the safety and effectiveness of the HM3 LVAS by demonstrating non-inferiority to the HMII LVAS (HMII) when used for the treatment of advanced, refractory, left ventricular heart failure.

Detailed description: The HM3 LVAS is intended to provide hemodynamic support in patients with advanced, refractory left ventricular heart failure; either for short term support, such as a bridge to cardiac transplantation (BTT) or myocardial recovery, or as long term support, such as destination therapy (DT). The HM3 is intended for use inside or outside the hospital.

Eligibility criteria: Inclusion Criteria:

1. Subject or legal representative has signed Informed Consent Form (ICF)
2. Age ≥ 18 years
3. BSA ≥ 1.2 m2
4. NYHA Class III with dyspnea upon mild physical activity, or NYHA Class IV
5. LVEF ≤ 25%
6. a) Inotrope dependent OR b) CI \< 2.2 L/min/m2, while not on inotropes and subjects 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
   * Advanced Heart Failure for at least 14 days AND dependent on intra-aortic balloon pump (IABP) for at least 7 days
7. Females of child bearing age must agree to use adequate contraception

Exclusion Criteria:

1. Etiology of heart failure (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. Presence of mechanical aortic valve that will not be either converted to a bioprosthesis or oversewn at the time of LVAD implant
6. History of any organ transplant
7. Platelet count \< 100,000 x 103/L (\< 100,000/ml)
8. Psychiatric disease/disorder, irreversible cognitive dysfunction or psychosocial issues that are likely to impair compliance with the study protocol and LVAS management
9. History of confirmed, untreated AAA \> 5 cm in diameter within 6 months of enrollment
10. Presence of an active, uncontrolled infection
11. Intolerance to anticoagulant or antiplatelet therapies or any other peri/post-operative therapy the investigator will require based upon the patients' health status
12. Presence of any one of the following risk factors for indications of severe end organ dysfunction or failure:

    1. An INR ≥ 2.0 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, and 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%) uncorrected carotid stenosis
    6. Serum creatinine ≥ 221 umol/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
13. Patient has moderate to severe aortic insufficiency without plans for correction during pump implant
14. Pre albumin \< 150 mg/L (15mg/dL) or Albumin \< 30g/L (3 g/dL) (if only one available) ; pre albumin \< 150 mg/L (15mg/dL) and Albumin \< 30g/L (3 g/dL) (if both available)
15. Planned Bi-VAD support prior to enrollment
16. Patient has known hypo or hyper coagulable states such as disseminated intravascular coagulation and heparin induced thrombocytopenia
17. Participation in any other clinical investigation that is likely to confound study results or affect the study
18. Any condition other than HF that could limit survival to less than 24 months

Primary outcomes:
measure: Short Term Primary End Point
timeFrame: The first 294 randomized Subjects will be followed for 6 months or to outcome (transplant, explant, or death), whichever occurs first.
measure: Long Term Primary End Point
timeFrame: The first 366 randomized Subjects will be followed for 24 months or to outcome (transplant, explant, or death), whichever occurs first.
Secondary outcomes:
measure: Powered Secondary End Point: Pump Replacement at Two Years
timeFrame: As they occur up to 24 months or to Outcome, whichever occurs first
measure: EuroQoL 5D-5L (EQ-5D-5L) Total Score
timeFrame: Baseline to 24 months
measure: EuroQol-5D-5L Visual Analogue Scale
timeFrame: Baseline to 24 months
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
timeFrame: Baseline to 24 months
measure: Six Minute Walk Test
timeFrame: Baseline to 24 months
measure: New York Heart Association (NYHA) Classification
timeFrame: Baseline to 24 months
measure: Rehospitalizations
timeFrame: From initial discharge to two years post-implant
measure: Adverse Event Rates
timeFrame: Two years post-implant
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Baptist Health Medical Center - Little Rock
state: Arkansas
city: Beverly Hills
country: United States
facility: Cedars Sinai Medical Center
state: California
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Sacramento
country: United States
facility: Sutter Memorial Hospital
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Gainesville
country: United States
facility: Shands Hospital @ University of Florida
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: IU Health/Methodist Hospital
state: Indiana
city: Indianapolis
country: United States
facility: St. Vincent Hospital
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky - Saha Cardiovascular Research Center
state: Kentucky
city: Louisville
country: United States
facility: Jewish Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Unversity Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Butterworth Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center, Fairview
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Mt. Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: INTEGRIS Baptist Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Hershey
country: United States
facility: Hershey
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: St. Thomas West Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Health Systems
state: Texas
city: Houston
country: United States
facility: Methodist Houston
state: Texas
city: Houston
country: United States
facility: Texas Heart Institute
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital and Clinics
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Richmond
country: United States
facility: Bon Secours St. Mary's Hospital
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Hospitals and Clinics
state: Wisconsin
city: Milwaukee
country: United States
facility: St. Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: Abbott
name: Daniel Crandall, PhD
role: STUDY_DIRECTOR
References:
citation: Mehra MR, Naka Y, Uriel N, Goldstein DJ, Cleveland JC Jr, Colombo PC, Walsh MN, Milano CA, Patel CB, Jorde UP, Pagani FD, Aaronson KD, Dean DA, McCants K, Itoh A, Ewald GA, Horstmanshof D, Long JW, Salerno C; MOMENTUM 3 Investigators. A Fully Magnetically Levitated Circulatory Pump for Advanced Heart Failure. N Engl J Med. 2017 Feb 2;376(5):440-450. doi: 10.1056/NEJMoa1610426. Epub 2016 Nov 16.
citation: Mehra MR, Goldstein DJ, Cleveland JC, Cowger JA, Hall S, Salerno CT, Naka Y, Horstmanshof D, Chuang J, Wang A, Uriel N. Five-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left Ventricular Assist Devices in the MOMENTUM 3 Randomized Trial. JAMA. 2022 Sep 27;328(12):1233-1242. doi: 10.1001/jama.2022.16197.
citation: Sheikh FH, Ravichandran AK, Goldstein DJ, Agarwal R, Ransom J, Bansal A, Kim G, Cleveland JC, Uriel N, Sheridan BC, Chomsky D, Patel SR, Dirckx N, Franke A, Mehra MR. Impact of Race on Clinical Outcomes After Implantation With a Fully Magnetically Levitated Left Ventricular Assist Device: An Analysis From the MOMENTUM 3 Trial. Circ Heart Fail. 2021 Oct;14(10):e008360. doi: 10.1161/CIRCHEARTFAILURE.120.008360. Epub 2021 Sep 16.
citation: Lundgren SW, Florescu DF, Zolty R. Reactivation of Cytomegalovirus Following Left Ventricular Assist Device Implantation: A Case-Control Study. ASAIO J. 2021 Apr 1;67(4):405-410. doi: 10.1097/MAT.0000000000001236.
citation: Saeed O, Colombo PC, Mehra MR, Uriel N, Goldstein DJ, Cleveland J, Connors JM, Najjar SS, Mokadam NA, Bansal A, Crandall DL, Sood P, Jorde UP. Effect of aspirin dose on hemocompatibility-related outcomes with a magnetically levitated left ventricular assist device: An analysis from the MOMENTUM 3 study. J Heart Lung Transplant. 2020 Jun;39(6):518-525. doi: 10.1016/j.healun.2020.03.001. Epub 2020 Mar 20.
citation: Patel CB, Blue L, Cagliostro B, Bailey SH, Entwistle JW, John R, Thohan V, Cleveland JC Jr, Goldstein DJ, Uriel N, Su X, Somo SI, Sood P, Mehra MR. Left ventricular assist systems and infection-related outcomes: A comprehensive analysis of the MOMENTUM 3 trial. J Heart Lung Transplant. 2020 Aug;39(8):774-781. doi: 10.1016/j.healun.2020.03.002. Epub 2020 Mar 20.
citation: Goldstein DJ, Naka Y, Horstmanshof D, Ravichandran AK, Schroder J, Ransom J, Itoh A, Uriel N, Cleveland JC Jr, Raval NY, Cogswell R, Suarez EE, Lowes BD, Kim G, Bonde P, Sheikh FH, Sood P, Farrar DJ, Mehra MR. Association of Clinical Outcomes With Left Ventricular Assist Device Use by Bridge to Transplant or Destination Therapy Intent: The Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) Randomized Clinical Trial. JAMA Cardiol. 2020 Apr 1;5(4):411-419. doi: 10.1001/jamacardio.2019.5323.
citation: Mehra MR, Uriel N, Naka Y, Cleveland JC Jr, Yuzefpolskaya M, Salerno CT, Walsh MN, Milano CA, Patel CB, Hutchins SW, Ransom J, Ewald GA, Itoh A, Raval NY, Silvestry SC, Cogswell R, John R, Bhimaraj A, Bruckner BA, Lowes BD, Um JY, Jeevanandam V, Sayer G, Mangi AA, Molina EJ, Sheikh F, Aaronson K, Pagani FD, Cotts WG, Tatooles AJ, Babu A, Chomsky D, Katz JN, Tessmann PB, Dean D, Krishnamoorthy A, Chuang J, Topuria I, Sood P, Goldstein DJ; MOMENTUM 3 Investigators. A Fully Magnetically Levitated Left Ventricular Assist Device - Final Report. N Engl J Med. 2019 Apr 25;380(17):1618-1627. doi: 10.1056/NEJMoa1900486. Epub 2019 Mar 17.
citation: Colombo PC, Mehra MR, Goldstein DJ, Estep JD, Salerno C, Jorde UP, Cowger JA, Cleveland JC Jr, Uriel N, Sayer G, Skipper ER, Downey FX, Ono M, Hooker R Jr, Anyanwu AC, Givertz MM, Mahr C, Topuria I, Somo SI, Crandall DL, Horstmanshof DA. Comprehensive Analysis of Stroke in the Long-Term Cohort of the MOMENTUM 3 Study. Circulation. 2019 Jan 8;139(2):155-168. doi: 10.1161/CIRCULATIONAHA.118.037231.
citation: Mehra MR, Salerno C, Naka Y, Uriel N, Cleveland JC, Horstmanshof D, Goldstein DJ; MOMENTUM 3 Investigators. A tale of the twist in the outflow graft: An analysis from the MOMENTUM 3 trial. J Heart Lung Transplant. 2018 Nov;37(11):1281-1284. doi: 10.1016/j.healun.2018.08.011. Epub 2018 Aug 24. No abstract available.
citation: Mehra MR, Salerno C, Cleveland JC, Pinney S, Yuzefpolskaya M, Milano CA, Itoh A, Goldstein DJ, Uriel N, Gulati S, Pagani FD, John R, Adamson R, Bogaev R, Thohan V, Chuang J, Sood P, Goates S, Silvestry SC. Healthcare Resource Use and Cost Implications in the MOMENTUM 3 Long-Term Outcome Study. Circulation. 2018 Oct 30;138(18):1923-1934. doi: 10.1161/CIRCULATIONAHA.118.035722.
citation: Mehra MR, Goldstein DJ, Uriel N, Cleveland JC Jr, Yuzefpolskaya M, Salerno C, Walsh MN, Milano CA, Patel CB, Ewald GA, Itoh A, Dean D, Krishnamoorthy A, Cotts WG, Tatooles AJ, Jorde UP, Bruckner BA, Estep JD, Jeevanandam V, Sayer G, Horstmanshof D, Long JW, Gulati S, Skipper ER, O'Connell JB, Heatley G, Sood P, Naka Y; MOMENTUM 3 Investigators. Two-Year Outcomes with a Magnetically Levitated Cardiac Pump in Heart Failure. N Engl J Med. 2018 Apr 12;378(15):1386-1395. doi: 10.1056/NEJMoa1800866. Epub 2018 Mar 11.
citation: Goldstein DJ, Mehra MR, Naka Y, Salerno C, Uriel N, Dean D, Itoh A, Pagani FD, Skipper ER, Bhat G, Raval N, Bruckner BA, Estep JD, Cogswell R, Milano C, Fendelander L, O'Connell JB, Cleveland J; MOMENTUM 3 Investigators. Impact of age, sex, therapeutic intent, race and severity of advanced heart failure on short-term principal outcomes in the MOMENTUM 3 trial. J Heart Lung Transplant. 2018 Jan;37(1):7-14. doi: 10.1016/j.healun.2017.11.001. Epub 2017 Nov 3.
citation: Cowger JA, Naka Y, Aaronson KD, Horstmanshof D, Gulati S, Rinde-Hoffman D, Pinney S, Adatya S, Farrar DJ, Jorde UP; MOMENTUM 3 Investigators. Quality of life and functional capacity outcomes in the MOMENTUM 3 trial at 6 months: A call for new metrics for left ventricular assist device patients. J Heart Lung Transplant. 2018 Jan;37(1):15-24. doi: 10.1016/j.healun.2017.10.019. Epub 2017 Oct 24.
citation: Uriel N, Colombo PC, Cleveland JC, Long JW, Salerno C, Goldstein DJ, Patel CB, Ewald GA, Tatooles AJ, Silvestry SC, John R, Caldeira C, Jeevanandam V, Boyle AJ, Sundareswaran KS, Sood P, Mehra MR. Hemocompatibility-Related Outcomes in the MOMENTUM 3 Trial at 6 Months: A Randomized Controlled Study of a Fully Magnetically Levitated Pump in Advanced Heart Failure. Circulation. 2017 May 23;135(21):2003-2012. doi: 10.1161/CIRCULATIONAHA.117.028303. Epub 2017 Apr 6.