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

Primary Purpose

Stem Cell Transplantation, Ventricular Dysfunction, Left

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Autologous human mesenchymal cells (hMSCs)

Autologous human bone marrow cells (hBMCs)

Placebo

About this trial

This is an interventional treatment trial for Stem Cell Transplantation focused on measuring Chronic Ischemic Left Ventricular Dysfunction

Eligibility Criteria

21 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Miami Miller School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Serial Creatine Kinase Values (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.

Ectopic Tissue Formation.

Number of Deaths

Change From Baseline in Distance Walked in Six-minutes (Six-minute Walk Test).

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.

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.

Data provided are with respect to the change from baseline at 12-months post-catheterization.

Full Information

NCT ID

NCT00768066

First Posted

October 3, 2008

Last Updated

November 9, 2015

Sponsor

University of Miami

Collaborators

The Emmes Company, LLC

1. Study Identification

Unique Protocol Identification Number

NCT00768066

Brief Title

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

Acronym

TAC-HFT

Official Title

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.

Study Type

Interventional

2. Study Status

Record Verification Date

November 2015

Overall Recruitment Status

Completed

Study Start Date

August 2008 (undefined)

Primary Completion Date

August 2012 (Actual)

Study Completion Date

September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Miami

Collaborators

The Emmes Company, LLC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Stem Cell Transplantation, Ventricular Dysfunction, Left

Keywords

Chronic Ischemic Left Ventricular Dysfunction

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

65 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

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

Arm Title

Arm Type

Experimental

Arm Description

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

Arm Title

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

Autologous human mesenchymal cells (hMSCs)

Intervention Description

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

Intervention Name(s)

Autologous human bone marrow cells (hBMCs)

Intervention Description

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

Intervention Name(s)

Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

Time Frame

one month post-catheterization

Secondary Outcome Measure Information:

Title

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

Title

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

Title

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

Title

Ectopic Tissue Formation.

Time Frame

12 months post-catheterization

Title

Number of Deaths

Time Frame

12-months post-catheterization

Title

Change From Baseline in Distance Walked in Six-minutes (Six-minute Walk Test).

Description

Data provided are with respect to the change from baseline at 12-months post-catheterization.

Time Frame

12 months post-catheterization

Title

Change From Baseline in the Minnesota Living With Heart Failure (MLHF) Questionnaire Total Score.

Description

Time Frame

12 months post-catheterization

Title

Percent Change From Baseline in Scar Mass as a Fraction of Left Ventricle Mass by Cardiac MRI or CT.

Description

Data provided are with respect to the change from baseline at 12-months post-catheterization.

Time Frame

12 Months post-catheterization

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Joshua M Hare, MD

Organizational Affiliation

University of Miami

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Richard P Schwarz, PhD

Organizational Affiliation

CV Ventures

Official's Role

Study Director

Facility Information:

Facility Name

University of Miami Miller School of Medicine

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

24247587

Citation

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.

Results Reference

result

PubMed Identifier

30005555

Citation

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.

Results Reference

derived

PubMed Identifier

21392602

Citation

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.

Results Reference

derived

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

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