The Transendocardial Autologous Cells (hMSC or hBMC) in Ischemic Heart Failure Trial (TAC-HFT)
| Status: | Completed |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 21 - 90 |
| Updated: | 4/21/2016 |
| Start Date: | August 2008 |
| End Date: | September 2013 |
A Phase I/II, Randomized, Double-Blinded, Placebo-Controlled Study of the Safety and Efficacy of Transendocardial Injection of Autologous Human Cells (Bone Marrow or Mesenchymal) in Patients With Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction.
The technique of transplanting progenitor cells into a region of damaged myocardium, termed
cellular cardiomyoplasty, is a potentially new therapeutic modality designed to replace or
repair necrotic, scarred, or dysfunctional myocardium. Ideally, graft cells should be
readily available, easy to culture to ensure adequate quantities for transplantation, and
able to survive in host myocardium; often a hostile environment of limited blood supply and
immunorejection. Whether effective cellular regenerative strategies require that
administered cells differentiate into adult cardiomyocytes and couple electromechanically
with the surrounding myocardium is increasingly controversial, and recent evidence suggests
that this may not be required for effective cardiac repair. Most importantly,
transplantation of graft cells should improve cardiac function and prevent adverse
ventricular remodeling. To date, a number of candidate cells have been transplanted in
experimental models, including fetal and neonatal cardiomyocytes, embryonic stem
cell-derived myocytes, tissue engineered contractile grafts, skeletal myoblasts, several
cell types derived from adult bone marrow, and cardiac precursors residing within the heart
itself. There has been substantial clinical development in the use of whole bone marrow and
skeletal myoblast preparations in studies enrolling both post-infarction patients, and
patients with chronic ischemic left ventricular dysfunction and heart failure. The effects
of bone-marrow derived mesenchymal stem cells (MSCs) have also been studies clinically.
Currently, bone marrow or bone marrow-derived cells represent highly promising modality for
cardiac repair. The totality of evidence from trials investigating autologous whole bone
marrow infusions into patients following myocardial infarction supports the safety of this
approach. In terms of efficacy, increases in ejection fraction are reported in the majority
of the trials.
Chronic ischemic left ventricular dysfunction resulting from heart disease is a common and
problematic condition; definitive therapy in the form of heart transplantation is available
to only a tiny minority of eligible patients. Cellular cardiomyoplasty for chronic heart
failure has been studied less than for acute MI, but represents a potentially important
alternative for this disease.
cellular cardiomyoplasty, is a potentially new therapeutic modality designed to replace or
repair necrotic, scarred, or dysfunctional myocardium. Ideally, graft cells should be
readily available, easy to culture to ensure adequate quantities for transplantation, and
able to survive in host myocardium; often a hostile environment of limited blood supply and
immunorejection. Whether effective cellular regenerative strategies require that
administered cells differentiate into adult cardiomyocytes and couple electromechanically
with the surrounding myocardium is increasingly controversial, and recent evidence suggests
that this may not be required for effective cardiac repair. Most importantly,
transplantation of graft cells should improve cardiac function and prevent adverse
ventricular remodeling. To date, a number of candidate cells have been transplanted in
experimental models, including fetal and neonatal cardiomyocytes, embryonic stem
cell-derived myocytes, tissue engineered contractile grafts, skeletal myoblasts, several
cell types derived from adult bone marrow, and cardiac precursors residing within the heart
itself. There has been substantial clinical development in the use of whole bone marrow and
skeletal myoblast preparations in studies enrolling both post-infarction patients, and
patients with chronic ischemic left ventricular dysfunction and heart failure. The effects
of bone-marrow derived mesenchymal stem cells (MSCs) have also been studies clinically.
Currently, bone marrow or bone marrow-derived cells represent highly promising modality for
cardiac repair. The totality of evidence from trials investigating autologous whole bone
marrow infusions into patients following myocardial infarction supports the safety of this
approach. In terms of efficacy, increases in ejection fraction are reported in the majority
of the trials.
Chronic ischemic left ventricular dysfunction resulting from heart disease is a common and
problematic condition; definitive therapy in the form of heart transplantation is available
to only a tiny minority of eligible patients. Cellular cardiomyoplasty for chronic heart
failure has been studied less than for acute MI, but represents a potentially important
alternative for this disease.
Inclusion Criteria:
- Diagnosis of chronic ischemic left ventricular dysfunction secondary to MI.
- Be a candidate for cardiac catheterization.
- Been treated with appropriate maximal medical therapy for heart failure or
post-infarction left ventricular dysfunction.
- Ejection fraction less than or equal to 50%.
- Able to perform a metabolic stress test.
Exclusion Criteria:
- Baseline glomerular filtration rate < 45 ml/min/1.73m2.
- Presence of a mechanical aortic valve or heart constrictive device.
- Documented presence of aortic stenosis (aortic stenosis graded as ≥+2 equivalent to
an orifice area of 1.5cm2 or less).
- Documented presence of moderate to severe aortic insufficiency (echocardiographic
assessment of aortic insufficiency graded as ≥+2).
- Evidence of a life-threatening arrhythmia (nonsustained ventricular tachycardia ≥ 20
consecutive beats or complete heart block) or QTc interval > 550 ms on screening ECG.
In addition; patients with sustained or a short run of ventricular tachycardia on ECG
or 48 hour Ambulatory ECG during the screening period will be removed from the
protocol.
- Documented unstable angina.
- AICD firing in the past 60 days prior to the procedure.
- Contra-indication to performance of a magnetic resonance imaging scan.
- Be eligible for or require coronary artery revascularization.
- Have a hematologic abnormality as evidenced by hematocrit < 25%, white blood cell <
2,500/ul or platelet values < 100,000/ul without another explanation.
- Have liver dysfunction, as evidenced by enzymes (ALT and AST) greater than three
times the ULN.
- Have a coagulopathy condition = (INR > 1.3) not due to a reversible cause.
- Known, serious radiographic contrast allergy.
- Known allergies to penicillin or streptomycin.
- Organ transplant recipient.
- Clinical history of malignancy within 5 years (i.e., patients with prior malignancy
must be disease free for 5 years), except curatively-treated basal cell carcinoma,
squamous cell carcinoma, or cervical carcinoma.
- Non-cardiac condition that limits lifespan to < 1 year.
- On chronic therapy with immunosuppressant medication.
- Serum positive for HIV, hepatitis BsAg, or non-viremic hepatitis C.
- Female patient who is pregnant, nursing, or of child-bearing potential and not using
effective birth control.
We found this trial at
1
site
1601 Northwest 12th Avenue
Miami, Florida 33136
Miami, Florida 33136
(305) 243-6545
University of Miami Miller School of Medicine The University of Miami Leonard M. Miller School...
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