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The Transendocardial Autologous Cells (hMSC or hBMC) in Ischemic Heart Failure Trial (TAC-HFT) (TAC-HFT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00768066
Recruitment Status : Completed
First Posted : October 7, 2008
Results First Posted : December 14, 2015
Last Update Posted : December 14, 2015
Sponsor:
Collaborator:
The Emmes Company, LLC
Information provided by (Responsible Party):
Joshua M Hare, University of Miami

Tracking Information
First Submitted Date  ICMJE October 3, 2008
First Posted Date  ICMJE October 7, 2008
Results First Submitted Date  ICMJE January 17, 2014
Results First Posted Date  ICMJE December 14, 2015
Last Update Posted Date December 14, 2015
Study Start Date  ICMJE August 2008
Actual Primary Completion Date August 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 7, 2009)
Incidence of TE-SAE Define as Composite of Death, Non-fatal MI, Stroke, Hospitalization for Worsening Heart Failure, Cardiac Perforation, Pericardial Tamponade, Ventricular Arrhythmias >15 Sec. or With Hemodynamic Compromise or Atrial Fibrillation [ Time Frame: one month post-catheterization ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 3, 2008)
Post-CABG surgery SAE proportion of patients experiencing sustained ventricular arrhythmias or sudden unexpected death or ectopic tissue formation by chest/abdomen/pelvis CT exam. [ Time Frame: Month 6 and Month 12 post-CABG ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 9, 2015)
  • Serial Troponin Values (Every 12 Hours for the First 48 Hours Post-catheterization). [ Time Frame: Measured every 12 hours for the first 48 hours post-catheterization ]
  • Serial Creatine Kinase Values (Every 12 Hours for the First 48 Hours Post-catheterization). [ Time Frame: Measured every 12 hours for the first 48 hours post-catheterization ]
  • Incidence of the Major Adverse Cardiac Events (MACE) Endpoint, Defined as the Composite Incidence of (1) Death, (2) Hospitalization for Heart Failure, or (3) Non-fatal Recurrent MI. [ Time Frame: 12 months post-catheterization ]
  • Ectopic Tissue Formation. [ Time Frame: 12 months post-catheterization ]
  • Number of Deaths [ Time Frame: 12-months post-catheterization ]
  • Change From Baseline in Distance Walked in Six-minutes (Six-minute Walk Test). [ Time Frame: 12 months post-catheterization ]
    Data provided are with respect to the change from baseline at 12-months post-catheterization.
  • Change From Baseline in the Minnesota Living With Heart Failure (MLHF) Questionnaire Total Score. [ Time Frame: 12 months post-catheterization ]
    Data provided are with respect to the change from baseline at 12-months post-catheterization. The Minnesota living with heart failure questionnaire uses a 6-point, zero to five, Likert scale. The total score is the sum of the 21 responses. The total score is considered the best measure of how heart failure and treatments impact a patients quality of life. The max score is 105, minimum score is 0. A lower score is considered a better quality of life.
  • Percent Change From Baseline in Scar Mass as a Fraction of Left Ventricle Mass by Cardiac MRI or CT. [ Time Frame: 12 Months post-catheterization ]
    Data provided are with respect to the change from baseline at 12-months post-catheterization.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 3, 2008)
  • MRI and echocardiographic-derived measures of left ventricular function: -- Difference between the baseline, 6-month, and 18-month infarct scar size (ISS)as determined by delayed contrast-enhanced MRI. [ Time Frame: Baseline and Month 6 and Month 12 post-CABG ]
  • MRI and echocardiographic-derived measures of left ventricular function: -- Difference between regional left ventricular function (region of MSC injection) as determined by MRI. [ Time Frame: Baseline and Month 6 and Month 12 post-CABG ]
  • MRI and echocardiographic-derived measures of left ventricular function: -- Difference between regional left ventricular wall thickening as determined by MRI. [ Time Frame: Baseline and Month 6 and Month 12 post-CABG ]
  • MRI and echocardiographic-derived measures of left ventricular function: -- Difference between left ventricular end diastolic wall thickness as determined by MRI and echocardiogram. [ Time Frame: Baseline and Month 6 and Month 12 post-CABG ]
  • MRI and echocardiographic-derived measures of left ventricular function: -- Difference between left ventricular ejection fraction, and end diastolic and end systolic volumes, as determined by MRI and echocardiogram. [ Time Frame: Baseline and Month 6 and Month 12 post-CABG ]
  • MRI and echocardiographic-derived measures of left ventricular function: -- Difference between the baseline, 6-month, and 18-month left ventricular regional myocardial perfusion as determined by MRI. [ Time Frame: During 6 month follow-up period post-CABG and at 12 months post-CABG ]
  • Peak VO2 (by treadmill determination). [ Time Frame: During 6 month follow-up period post-CABG and at 12 months post-CABG ]
  • Six-minute walk test. [ Time Frame: During 6 month follow-up period post-CABG and at 12 months post-CABG ]
  • NYHA functional class. [ Time Frame: During 6 month follow-up period post-CABG and at 12 months post-CABG ]
  • Minnesota Living with Heart Failure (MLHF) questionnaire. [ Time Frame: During 6 month follow-up period post-CABG and at 12 months post-CABG ]
  • Incidence of the Major Adverse Cardiac Events (MACE) Endpoint, Defined as the Composite Incidence of (1) Death, (2) Hospitalization for Heart Failure, or (3) Non-fatal Recurrent MI. [ Time Frame: During 6 month follow-up period post-CABG and at 12 months post-CABG ]
  • Treatment emergent adverse event (AE) rates. [ Time Frame: During 6 month follow-up period post-CABG and at 12 months post-CABG ]
  • 48-hour ambulatory ECG recordings. [ Time Frame: During 6 month follow-up period post-CABG and at 12 months post-CABG ]
  • Hematology, clinical chemistry and urinalysis values. [ Time Frame: During 6 month follow-up period post-CABG and at 12 months post-CABG ]
  • Pulmonary function (measured by the forced expiratory volume in 1 second [FEV1]). [ Time Frame: During 6 month follow-up period post-CABG and at 12 months post-CABG ]
  • Serial troponin and CK-MB values (every 12 hours for the first 48 hours post CABG). [ Time Frame: Measured every 12 hours for the first 48 hours post-CABG ]
  • Post-CABG surgery echocardiogram (day 2 post-op). [ Time Frame: Day 2 post-CABG ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Transendocardial Autologous Cells (hMSC or hBMC) in Ischemic Heart Failure Trial (TAC-HFT)
Official Title  ICMJE 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.
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Stem Cell Transplantation
  • Ventricular Dysfunction, Left
Intervention  ICMJE
  • Biological: Autologous human mesenchymal cells (hMSCs)
    Participants will receive 40 million cells/mL delivered in either a dose of 0.25 mL per injection for a total of 1 x 108 (100 million) hMSCs x 10 injections or a dose of 0.5 mL per injection for a total of 2 x 108 (200 million) x 10 injections. The injections will be administered transendocardially during cardiac catheterization using the Biocardia Helical Infusion Catheter.
  • Biological: Autologous human bone marrow cells (hBMCs)
    Participants will receive 40 million cells/mL delivered in either a dose of 0.25 mL per injection for a total of 1 x 108 (100 million) hBMCs x 10 injections or a dose of 0.5 mL per injection for a total of 2 x 108 (200 million) x 10 injections. The injections will be administered transendocardially during cardiac catheterization using the Biocardia Helical Infusion Catheter.
  • Biological: Placebo
    Participants will receive 0.5 mL injections of phosphate-buffered saline (PBS) and 1% human serum albumin (HAS) x 10 injections. The injections will be administered transendocardially during cardiac catheterization using the Biocardia Helical Infusion Catheter.
Study Arms  ICMJE
  • Experimental: 1
    Participants will receive an injection of 100 million or 200 million autologous human mesenchymal stem cells (hMSCs).
    Intervention: Biological: Autologous human mesenchymal cells (hMSCs)
  • Experimental: 2
    Participants will receive an injection of 100 million or 200 million autologous human bone marrow cells (hBMCs).
    Intervention: Biological: Autologous human bone marrow cells (hBMCs)
  • Placebo Comparator: 3
    Participants will receive a placebo injection of phosphate-buffered saline (PBS) and 1% human serum albumin (HAS).
    Intervention: Biological: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 9, 2015)
65
Original Estimated Enrollment  ICMJE
 (submitted: October 3, 2008)
60
Actual Study Completion Date  ICMJE September 2013
Actual Primary Completion Date August 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00768066
Other Study ID Numbers  ICMJE 20070443
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Joshua M Hare, University of Miami
Study Sponsor  ICMJE University of Miami
Collaborators  ICMJE The Emmes Company, LLC
Investigators  ICMJE
Principal Investigator: Joshua M Hare, MD University of Miami
Study Director: Richard P Schwarz, PhD CV Ventures
PRS Account University of Miami
Verification Date November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP