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

NCT ID: NCT00768066

Last Updated: 2015-12-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-31
• Study Completion Date: 2013-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1

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

Group Type: EXPERIMENTAL

Autologous human mesenchymal cells (hMSCs)

Intervention Type: 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.

2

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

Group Type: EXPERIMENTAL

Autologous human bone marrow cells (hBMCs)

Intervention Type: 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.

3

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Emmes Company, LLC

INDUSTRY

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Joshua M Hare

Director, Interdisciplinary Stem Cell Institute

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joshua M Hare, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Richard P Schwarz, PhD

Role: STUDY_DIRECTOR

CV Ventures

Locations

University of Miami Miller School of Medicine

Miami, Florida, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 24247587 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30005555 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21392602 (View on PubMed)

Other Identifiers

20070443

Identifier Type: -

Identifier Source: org_study_id