Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients

• ClinicalTrials.gov Identifier: NCT02362646
• Recruitment Status: Completed
• First Posted: February 13, 2015
• Results First Posted: November 26, 2019
• Last Update Posted: November 26, 2019
• Sponsor: Annetine Gelijns
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Annetine Gelijns, Icahn School of Medicine at Mount Sinai

Tracking Information

• First Submitted Date: February 9, 2015
• First Posted Date: February 13, 2015
• Results First Submitted Date: November 7, 2019
• Results First Posted Date: November 26, 2019
• Last Update Posted Date: November 26, 2019
• Study Start Date: July 2015
• Actual Primary Completion Date: August 10, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 7, 2019)

• Number of Temporary Weans From LVAD Support Tolerated [ Time Frame: up to 6 months ]
  functional status, defined by the number of temporary weans from LVAD support tolerated over the 6 months post-randomization. A successful wean is the ability to tolerate temporary weaning from LVAD support for 30 minutes without sustained symptoms of worsening heart failure. Wean failures are defined as inability to tolerate the temporary wean for 30 minutes; death; or patient too unstable, in the judgment of the primary heart failure cardiologist, to tolerate the wean attempt.
• Number of Participants With Adverse Events [ Time Frame: up to 6 months ]
  Safety as assessed by number of study intervention-related adverse events

Original Primary Outcome Measures (submitted: February 12, 2015)

• Functional Status [ Time Frame: up to 12 months ]
  functional status, defined by the number of temporary weans from LVAD support tolerated over the 12 months post-randomization. A successful wean is the ability to tolerate temporary weaning from LVAD support for 30 minutes without sustained symptoms of worsening heart failure. Wean failures are defined as inability to tolerate the temporary wean for 30 minutes; death; or patient too unstable, in the judgment of the primary heart failure cardiologist, to tolerate the wean attempt.
• Number of participants with adverse events [ Time Frame: up to 12 months ]
  Safety: Incidence of the study intervention-related adverse events

Current Secondary Outcome Measures (submitted: November 7, 2019)

• Physiologic Assessments [ Time Frame: up to 12 months ]
  Echocardiographic assessments of the myocardial size and function by transthoracic echocardiography with LVAD at full support, and as tolerated following 6-Minute Walk Test (MWT) while weaned from LVAD support (for patients who tolerate wean from LVAD support for 30 minutes)
• Histopathological Assessments of Myocardial Tissue [ Time Frame: up to 12 months ]
• Overall Survival [ Time Frame: up to 12 months ]
• Change in Quality of Life (QoL) [ Time Frame: 6 months and 12 months ]
  Quality of life will be assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ), a widely used tool in heart failure populations, and the Short Form 12 (SF12), a widely used overall health status measure.
• Hopkins Verbal Learning Test [ Time Frame: 3 months and 12 months ]
  Cognitive performance will be assessed Hopkins Verbal Learning Test. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
• Trailmaking Tests A and B [ Time Frame: 3 months and 12 months ]
  Cognitive performance will be assessed using Trailmaking Tests A and B. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
• MCG Complex Figures [ Time Frame: 3 months and 12 months ]
  Cognitive performance will be assessed using the MCG Complex Figures. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
• Digit Span [ Time Frame: 3 months and 12 months ]
  Cognitive performance will be assessed using the MCG Complex Figures. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
• Digit Symbol Substitution Test [ Time Frame: 3 months and 12 months ]
  Cognitive performance will be assessed using the Digit Symbol Substitution Test. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
• Controlled Oral Word Association [ Time Frame: 3 months and 12 months ]
  Cognitive performance will be assessed using the Controlled Oral Word Association. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
• Length of Stay [ Time Frame: up to 12 months ]
  Length of stay of index hospitalization
• Hospitalizations [ Time Frame: up to 12 months ]
  Frequency and cause of readmissions
• Hospital Costs [ Time Frame: up to 12 months ]
  Hospital resource use
• Functional Status [ Time Frame: up to 12 months ]
  functional status, defined by the number of temporary weans from LVAD support tolerated

Original Secondary Outcome Measures (submitted: February 12, 2015)

• Physiologic Assessments [ Time Frame: up to 12 months ]
  Echocardiographic assessments of the myocardial size and function by transthoracic echocardiography with LVAD at full support, and as tolerated following 6-Minute Walk Test (MWT) while weaned from LVAD support (for patients who tolerate wean from LVAD support for 30 minutes)
• Histopathological assessments of myocardial tissue [ Time Frame: up to 12 months ]
• Overall Survival [ Time Frame: up to 12 months ]
• Change in Quality of Life (QoL) [ Time Frame: 6 months and 12 months ]
  Quality of life will be assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ), a widely used tool in heart failure populations, and the Short Form 12 (SF12), a widely used overall health status measure.
• Hopkins Verbal Learning Test [ Time Frame: 3 months and 12 months ]
  Cognitive performance will be assessed Hopkins Verbal Learning Test. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
• Trailmaking Tests A and B [ Time Frame: 3 months and 12 months ]
  Cognitive performance will be assessed using Trailmaking Tests A and B. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
• MCG Complex Figures [ Time Frame: 3 months and 12 months ]
  Cognitive performance will be assessed using the MCG Complex Figures. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
• Digit Span [ Time Frame: 3 months and 12 months ]
  Cognitive performance will be assessed using the MCG Complex Figures. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
• Digit Symbol Substitution Test [ Time Frame: 3 months and 12 months ]
  Cognitive performance will be assessed using the Digit Symbol Substitution Test. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
• Controlled Oral Word Association [ Time Frame: 3 months and 12 months ]
  Cognitive performance will be assessed using the Controlled Oral Word Association. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
• Length of Stay [ Time Frame: up to 12 months ]
  Length of stay of index hospitalization
• Hospitalizations [ Time Frame: up to 12 months ]
  Frequency and cause of readmissions
• Hospital Costs [ Time Frame: up to 12 months ]
  Hospital resource use

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients
• Official Title: Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients
• Brief Summary: The main purpose of this research is to determine whether injecting mesenchymal precursor cells (MPC) into the heart during surgery to implant a left ventricular assist device (LVAD) is safe. MPCs are normally present in human bone marrow and have been shown to increase the development of blood vessels and new heart muscle cells in the heart. In addition, this research is being done to test whether injecting the MPCs into the heart is effective in improving heart function.
• Detailed Description: Intramyocardial injection of mesenchymal precursor cells (MPC) in patients with advanced heart failure who are treated with left ventricular assist device (LVAD) implantation may result in a renewable source of proliferating functional cardiomyocytes; induce development of capillaries and larger-size blood vessels to supply oxygen and nutrients to endogenous myocardium and newly-implanted cardiomyocytes; and release factors capable of paracrine signaling.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Heart Failure
• Cardiomyopathy
• Ventricular Dysfunction

Intervention

• Biological: MPC Intramyocardial Injection
  Intramyocardial injection of 150 million mesenchymal precursor cells at the time of LVAD implantation
  Other Names:

  • Mesenchymal Precursor Cell Injection
  • RevascorTM
• Drug: Control Solution
  Other Names:

  • 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO
  • Cryoprotective media

Study Arms

• Experimental: MPC Intramyocardial Injection
  Intramyocardial injections of 150 million MPCs
  Intervention: Biological: MPC Intramyocardial Injection
• Sham Comparator: Control Solution
  Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO
  Intervention: Drug: Control Solution

• Publications *: Yau TM, Pagani FD, Mancini DM, Chang HL, Lala A, Woo YJ, Acker MA, Selzman CH, Soltesz EG, Kern JA, Maltais S, Charbonneau E, Pan S, Marks ME, Moquete EG, O'Sullivan KL, Taddei-Peters WC, McGowan LK, Green C, Rose EA, Jeffries N, Parides MK, Weisel RD, Miller MA, Hung J, O'Gara PT, Moskowitz AJ, Gelijns AC, Bagiella E, Milano CA; Cardiothoracic Surgical Trials Network. Intramyocardial Injection of Mesenchymal Precursor Cells and Successful Temporary Weaning From Left Ventricular Assist Device Support in Patients With Advanced Heart Failure: A Randomized Clinical Trial. JAMA. 2019 Mar 26;321(12):1176-1186. doi: 10.1001/jama.2019.2341. Erratum In: JAMA. 2019 Sep 3;322(9):895.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 9, 2016): 159
• Original Estimated Enrollment (submitted: February 12, 2015): 120
• Actual Study Completion Date: August 23, 2019
• Actual Primary Completion Date: August 10, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Signed informed consent, inclusive of release of medical information, and Health Insurance Portability and Accountability Act (HIPAA) documentation
• Age 18 years or older
• If the subject or partner is of childbearing potential, he or she must be willing to use adequate contraception (hormonal or barrier method or abstinence) from the time of screening and for a period of at least 16 weeks after procedure
• Female subjects of childbearing potential must have a negative serum pregnancy test at screening
• Admitted to the clinical center at the time of randomization
• Clinical indication and accepted candidate for implantation of an FDA-approved (US sites only) or Health Canada-approved (Canadian sites only) implantable, non-pulsatile LVAD as a bridge to transplantation or for destination therapy.

Exclusion Criteria:

• Planned percutaneous LVAD implantation
• Anticipated requirement for biventricular mechanical support

• Concomitant arrhythmia ablation at time of LVAD implantation

  -- Planned aortic valve intervention for aortic insufficiency at the time of LVAD implantation

• Cardiothoracic surgery within 30 days prior to randomization
• Spontaneous myocardial infarction related to ischemia due to a primary coronary event such as unstable plaque rupture, erosion or dissection within 30 days prior to randomization
• Prior cardiac transplantation, LV reduction surgery, or cardiomyoplasty
• Acute reversible cause of heart failure (e.g. myocarditis, profound hypothyroidism)
• Stroke within 30 days prior to randomization
• Platelet count < 100,000/ul within 24 hours prior to randomization
• Acute infectious process: acute bacterial, fungal, or viral disease OR acute exacerbation of chronic infectious disease such as hepatitis
• Presence of >10% anti-HLA antibody titers with known specificity to MPC donor HLA antigens
• A known hypersensitivity to dimethyl sulfoxide (DMSO), murine, and/or bovine products
• History of a known active malignancy within the past 3 years except for localized prostate cancer, cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that has been definitively treated
• Presence of human immunodeficiency virus (HIV)
• Received investigational intervention within 30 days prior to randomization
• Treatment and/or an incomplete follow-up treatment of any investigational cell based therapy within 6 months prior to randomization
• Active participation in other research therapy for cardiovascular repair/regeneration
• Prior recipient of stem precursor cell therapy for cardiac repair
• Pregnant or breastfeeding at time of randomization.
• History of known or suspected hypercoagulable state in the opinion of the investigator

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT02362646
• Other Study ID Numbers: GCO 08-1078-0008; 2U01HL088942-07 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Annetine Gelijns, Icahn School of Medicine at Mount Sinai
• Original Responsible Party: Same as current
• Current Study Sponsor: Annetine Gelijns
• Original Study Sponsor: Same as current
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Study Chair: Patrick O'Gara, MD; Brigham and Women's Hospital
• Study Chair: Richard Weisel, MD; Toronto General Hospital

• PRS Account: Icahn School of Medicine at Mount Sinai
• Verification Date: November 2019