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

NCT00768066 | Completed Phase 1 Results DMC

• 1 other identifier: 20070443
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

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.

Conditions

Stem Cell Transplantation; Ventricular Dysfunction, Left

Keywords

Chronic Ischemic Left Ventricular Dysfunction

Outcome Measures

Primary Outcomes (1)

• 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

  one month post-catheterization

Secondary Outcomes (8)

• Serial Troponin Values (Every 12 Hours for the First 48 Hours Post-catheterization).

  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).

  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.

  12 months post-catheterization

• Ectopic Tissue Formation.

  12 months post-catheterization

• Number of Deaths

  12-months post-catheterization

Study Arms (3)

1

EXPERIMENTAL

Participants will receive an injection of 100 million or 200 million autologous human mesenchymal stem cells (hMSCs).

Biological: Autologous human mesenchymal cells (hMSCs)

2

EXPERIMENTAL

Participants will receive an injection of 100 million or 200 million autologous human bone marrow cells (hBMCs).

Biological: Autologous human bone marrow cells (hBMCs)

3

PLACEBO COMPARATOR

Participants will receive a placebo injection of phosphate-buffered saline (PBS) and 1% human serum albumin (HAS).

Biological: Placebo

Interventions

Autologous human mesenchymal cells (hMSCs) BIOLOGICAL

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.

1

Autologous human bone marrow cells (hBMCs) BIOLOGICAL

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.

2

Placebo BIOLOGICAL

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.

3

Eligibility Criteria

• Age: 21 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Miami: lead
• The Emmes Company, LLC: collaborator

Study Sites (1)

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Related Publications (3)

• Heldman AW, DiFede DL, Fishman JE, Zambrano JP, Trachtenberg BH, Karantalis V, Mushtaq M, Williams AR, Suncion VY, McNiece IK, Ghersin E, Soto V, Lopera G, Miki R, Willens H, Hendel R, Mitrani R, Pattany P, Feigenbaum G, Oskouei B, Byrnes J, Lowery MH, Sierra J, Pujol MV, Delgado C, Gonzalez PJ, Rodriguez JE, Bagno LL, Rouy D, Altman P, Foo CW, da Silva J, Anderson E, Schwarz R, Mendizabal A, Hare JM. Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial. JAMA. 2014 Jan 1;311(1):62-73. doi: 10.1001/jama.2013.282909.

  PMID: 24247587 RESULT

• Tompkins BA, Rieger AC, Florea V, Banerjee MN, Natsumeda M, Nigh ED, Landin AM, Rodriguez GM, Hatzistergos KE, Schulman IH, Hare JM. Comparison of Mesenchymal Stem Cell Efficacy in Ischemic Versus Nonischemic Dilated Cardiomyopathy. J Am Heart Assoc. 2018 Jul 12;7(14):e008460. doi: 10.1161/JAHA.117.008460.

  PMID: 30005555 DERIVED

• Trachtenberg B, Velazquez DL, Williams AR, McNiece I, Fishman J, Nguyen K, Rouy D, Altman P, Schwarz R, Mendizabal A, Oskouei B, Byrnes J, Soto V, Tracy M, Zambrano JP, Heldman AW, Hare JM. Rationale and design of the Transendocardial Injection of Autologous Human Cells (bone marrow or mesenchymal) in Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction (TAC-HFT) trial: A randomized, double-blind, placebo-controlled study of safety and efficacy. Am Heart J. 2011 Mar;161(3):487-93. doi: 10.1016/j.ahj.2010.11.024.

  PMID: 21392602 DERIVED

MeSH Terms

Conditions

Ventricular Dysfunction, Left

Condition Hierarchy (Ancestors)

Ventricular Dysfunction; Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Adam Mendizabal, Biostatistician
• Organization: The EMMES Corporation

amendizabal@emmes.com

301-251-1161

Study Officials

• Joshua M Hare, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

• Richard P Schwarz, PhD

  CV Ventures

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Interdisciplinary Stem Cell Institute

Study Record Dates

• First Submitted: October 3, 2008
• First Posted: October 7, 2008
• Study Start: August 1, 2008
• Primary Completion: August 1, 2012
• Study Completion: September 1, 2013
• Last Updated: December 14, 2015
• Results First Posted: December 14, 2015

Record last verified: 2015-11

Locations

US (1)