LVAD and Stem Cells

Principal Investigator: Craig Selzman
Keywords: Heart Failure , LVAD , Stem Cells , Bridge to Transplant , Destination Therapy , Myocardial Recovery Department: Cardiothoracic Division
IRB Number: 00078873 Co Investigator: Stavros Drakos
Specialty: Cardiology, Cardiothoracic Surgery, Cardiothoracic Surgery, Cardiothoracic Surgery, Cardiology, Cardiology, Cardiothoracic Surgery
Sub Specialties: Heart Failure, Heart Stem Cell Therapy, Cardiac Mechanical Support, Heart Failure, Echocardiography, Heart Transplant, Heart Transplant
Recruitment Status: Active, not recruiting

Contact Information

Ashley Elmer
ashley.elmer@hsc.utah.edu
801-585-6775

Brief Summary

This is a prospective, multi-center, double-blind, randomized (2:1), single dose cohort, sham procedure controlled trial to evaluate the safety and efficacy of injecting a dose of 150 M allogeneic MPCs into the native myocardium of LVAD recipients. Patients with advanced heart failure, either ischemic or non-ischemic etiology, implanted with an LVAD as either BTT or DT may be eligible to participate in the trial. FDA-approved LVADs will be utilized at US sites, and Health Canada-approved LVADs will be utilized at Canadian sites. Sample size is 159 patients randomized in a 2:1 allocation to intramyocardial injection of study product or control (cryoprotective media alone) at the time of LVAD implantation:

  • Group 1 (n=106): 150 million allogeneic MPCs (Mesoblast, Inc)
  • Group 2 (n=53): 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO (control)

The primary objectives of this trial are to evaluate the safety and efficacy of injecting MPCs (150 million dose) into the native myocardium of LVAD recipients. The secondary objectives are to explore the functional and physiologic effects of injecting MPCs (150 million dose) into the native myocardium of LVAD recipients.

The primary safety endpoint of this study is the incidence of potential study intervention-related adverse events (infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization syndrome).

The primary efficacy endpoint of this study is functional status, while temporarily weaned from LVAD support, over the 6 months post randomization. Functional status is defined by the ability to tolerate wean from LVAD support to low flow for 30 minutes.

Secondary endpoints include safety, survival, functional status over 6 & 12 months, and physiologic assessments.

All patients will be followed until cardiac transplantation (for bridge to transplant patients) or until 24 months post randomization, whichever comes first.

Inclusion Criteria

1. Admitted to the clinical center at the time of randomization

2. 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-transplant or for destination therapy

Exclusion Criteria

1. Planned percutaneous LVAD implantation;

2. Anticipated requirement for biventricular mechanical support;

3. Arrhythmia ablation at the time of LVAD implantation;

4. Planned aortic valve intervention for aortic insufficiency at the time of LVAD implantation;

5. Cardiothoracic surgery within 30 days prior to randomization;

6. 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;

7. Prior cardiac transplantation, LV reduction surgery, or cardiomyoplasty

8. Acute reversible cause of heart failure (e.g. myocarditis, profound hypothyroidism);

9. Stroke within 30 days prior to randomization;

10. Platelet count < 100,000/mcL within 24 hours prior to randomization;

11. Acute infectious process: acute bacterial, fungal or viral disease OR acute exacerbation of chronic infectious disease such as hepatitis ;

12. Presence of >10% anti-HLA antibody titers with known specificity to MPC donor HLA antigens;

13. A known hypersensitivity to dimethyl sulfoxide (DMSO), murine, and/or bovine products;

14. 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 definitively been treated;

15. Presence of human immunodeficiency virus (HIV);

16. Received investigational intervention within 30 days of randomization;

17. Treatment and/or an incomplete follow-up treatment of any investigational cell based therapy within 6 months prior to randomization;

18. Active participation in other research therapy for cardiovascular repair/regeneration;

19. Prior recipient of stem precursor cell therapy for cardiac repair;

20. Pregnant or breastfeeding at time of randomization;

21. History of known or suspected hypercoagulable state in the opinion of the investigator