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The Transendocardial Autologous Cells (hMSC) or (hMSC) and (hCSC) in Ischemic Heart Failure Trial. (TAC-HFT-II)

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ClinicalTrials.gov Identifier: NCT02503280
Recruitment Status : Not yet recruiting
First Posted : July 20, 2015
Last Update Posted : December 24, 2018
Sponsor:
Information provided by (Responsible Party):
Joshua M Hare, University of Miami

Brief Summary:

Before initiating the full randomized study, a Pilot Safety Phase will be performed. In this phase the composition of cells administered via the Biosense Webster MyoStar NOGA Injection Catheter System will be tested. The randomized portion of the study will be conducted after a full review of the safety data from the pilot Phase by the Data safety monitoring board.

Following the Pilot Phase of five (5) Fifty (50) patients scheduled to undergo cardiac catheterization and meeting all inclusion/exclusion criteria will be evaluated at baseline.

Patients will be randomized in a 2:2:1 ratio to one of three Treatment Strategies.


Condition or disease Intervention/treatment Phase
Chronic Ischemic Left Ventricular Dysfunction Myocardial Infarction Drug: Autologous hMSCs Drug: Autologous Human C-Kit CSCs II Drug: Placebo Device: Biosense Webster MyoStar NOGA Injection Catheter System Phase 1 Phase 2

Detailed Description:

A Phase I/II, Randomized, Placebo-Controlled Study of the Safety and Efficacy of Transendocardial Injection of Autologous Human Cells (Mesenchymal or the combination of MSC and Cardiac Stem Cells) in Patients With Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction.

A total of 55 subjects participating, with 5 in the pilot phase and 50 in the randomized phase.

Patients with chronic ischemic left ventricular dysfunction and heart failure secondary to MI scheduled to undergo cardiac catheterization.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: A Phase I/II, Randomized, Placebo-Controlled Study of the Safety and Efficacy of Transendocardial Injection of Autologous Human Cells (Mesenchymal or the Combination of MSC and Cardiac Stem Cells) in Patients With Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction.
Estimated Study Start Date : March 1, 2025
Estimated Primary Completion Date : March 2030
Estimated Study Completion Date : March 2032

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group A - Autologous hMSCs
Autologous hMSCs: 40 million cells/ml delivered in 0.5 ml injection volumes times 10 injections for a total of 2 x 10^8 (200 million) hMSCs. The Biosense Webster MyoStar NOGA Injection Catheter System will be used in the delivery of the study drug.
Drug: Autologous hMSCs
Autologous hMSCs: 40 million cells/ml delivered in 0.5 ml injection volumes times 10 injections for a total of 2 x 10^8 (200 million) hMSCs.
Other Name: Autologous Human Mesenchymal Stem Cells (hMSCs)

Device: Biosense Webster MyoStar NOGA Injection Catheter System
Biosense Webster MyoStar NOGA Injection Catheter System will be used to administer the study drug
Other Name: NOGA

Experimental: Group B - Autologous Human C-Kit CSCs II
Autologous hMSCs PLUS autologous C-Kit hCSCs: Mixture of 39.8 million hMSCs and 0.2 million C-Kit hCSCs/ml delivered in 0.5 ml injection volumes times 10 injections for a total of 1.99 x 10^8 (199 million) hMSCs and 1 million C-Kit hCSCs.The Biosense Webster MyoStar NOGA Injection Catheter System will be used in the delivery of the study drug.
Drug: Autologous Human C-Kit CSCs II
Autologous hMSCs PLUS autologous C-Kit hCSCs: Mixture of 39.8 million hMSCs and 0.2 million C-Kit hCSCs/ml delivered in 0.5 ml injection volumes times 10 injections for a total of 1.99 x 10^8 (199 million) hMSCs and 1 million C-Kit hCSCs.
Other Name: Autologous Human C-Kit Cardiac Stem Cells (CSCs) II

Device: Biosense Webster MyoStar NOGA Injection Catheter System
Biosense Webster MyoStar NOGA Injection Catheter System will be used to administer the study drug
Other Name: NOGA

Placebo Comparator: Placebo
Placebo (ten 0.5 ml injections of phosphate-buffered saline [PBS] and 1% human serum albumin [HSA]).The Biosense Webster MyoStar NOGA Injection Catheter System will be used in the delivery of the study drug.
Drug: Placebo
Placebo (ten 0.5 ml injections of phosphate-buffered saline [PBS] and 1% human serum albumin [HSA]).

Device: Biosense Webster MyoStar NOGA Injection Catheter System
Biosense Webster MyoStar NOGA Injection Catheter System will be used to administer the study drug
Other Name: NOGA




Primary Outcome Measures :
  1. Incidence of any treatment emergent serious adverse events (TE-SAEs) [ Time Frame: One Month post-catheterization ]
    Incidence (at one month post-catheterization) of any treatment-emergent serious adverse events (TE-SAEs), defined as the composite of: death, non-fatal MI, stroke, hospitalization for worsening heart failure, cardiac perforation, pericardial tamponade, sustained ventricular arrhythmias (characterized by ventricular arrhythmias lasting longer than 15 seconds or with hemodynamic compromise), or atrial fibrillation.


Secondary Outcome Measures :
  1. Treatment Emergent adverse event rates [ Time Frame: At 6 Month and 12 Month visit ]
    Rate of adverse events occurring ad

  2. Ectopic tissue formation [ Time Frame: At 6 Month and 12 Month visit ]
    Ectopic tissue formation (as identified from MRI scans of the chest, abdomen, & pelvis).

  3. 48-hour ambulatory electrocardiogram (ECG) recordings. [ Time Frame: At 6 Month and 12 Month visit ]
    Electrocardiogram (ECG) recordings measured over 48 Hours

  4. Hematology value changes post-catheterization [ Time Frame: At 6 Month and 12 Month visit ]
    Hematology value changes will be observed at the 6 month and 12 month visit post-catheterization.

  5. Urinalysis results changes post-catheterization [ Time Frame: At 6 Month and 12 Month visit ]
    Urinalysis results changes will be observed at the 6 month and 12 month visit post-catheterization.

  6. Clinical chemistry values post-catheterization [ Time Frame: At 6 Month and 12 Month visit ]
    Clinical chemistry value changes will be observed at the 6 month and 12 month visit post-catheterization.

  7. Pulmonary function [ Time Frame: At 6 Month and 12 Month visit ]
    Pulmonary function - forced expiratory volume in 1 second (FEV1) results.

  8. Serial troponin I values [ Time Frame: Every 12 hours for the first 48 hours post-cardiac catheterization ]
    Serial troponin I values (every 12 hours for first 48 hours post-cardiac catheterization).

  9. Creatine kinase-MB (CK-MB) value changes post-catheterization [ Time Frame: Every 12 hours for first 48 hours post-cardiac catheterization ]
    CK-MB values (every 12 hours for first 48 hours post-cardiac catheterization).

  10. Post-cardiac catheterization echocardiogram. [ Time Frame: Day 1 Post Echocardiogram ]
    Echocardiogram performed after cardiac catheterization

  11. Magnetic resonance imaging (MRI) measures of infarct scar size (ISS) [ Time Frame: At 6 Month and 12 Month visit ]
    Document Infarct Scar Size (ISS) via Magnetic Resonance imaging (MRI)

  12. Echocardiographic measures of infarct scar size (ISS) [ Time Frame: At 6 Month and 12 Month visit ]
    Document Infarct Scar Size (ISS) via echocardiographic procedure

  13. Magnetic resonance imaging (MRI) of Left Regional Ventricular Function [ Time Frame: At 6 Month and 12 Month visit ]
    Document Left Regional Ventricular Function via Magnetic Resonance imaging (MRI)

  14. Echocardiographic measures of Left Regional Ventricular Function [ Time Frame: At 6 Month and 12 Month visit ]
    Document Left Regional Ventricular Function via echocardiographic procedure

  15. Magnetic resonance imaging (MRI) of Global Ventricular Function [ Time Frame: At 6 Month and 12 Month visit ]
    Document Global Ventricular Function via Magnetic Resonance imaging (MRI)

  16. Echocardiographic measures of Global Ventricular Function [ Time Frame: At 6 Month and 12 Month visit ]
    Document Global Ventricular Function via echocardiographic procedure

  17. Tissue perfusion measured by MRI. [ Time Frame: At 6 Month and 12 Month visit ]
    Measure Tissue Perfusion via Magnetic Resonance imaging (MRI)

  18. Peak oxygen consumption (Peak VO2) (by treadmill determination). [ Time Frame: At 6 Month and 12 Month visit ]
    Peak VO2 Oxygen Consumption determined by utilizing treadmill

  19. Six-minute walk test. [ Time Frame: At 6 Month and 12 Month visit ]
    Evaluate Functional Capacity via the Six Minute Walk Test

  20. New York Heart Association (NYHA) functional class. [ Time Frame: At 6 Month and 12 Month visit ]
    Evaluate Functional Capacity via New York Heart Association (NYHA) Class Determination

  21. Minnesota Living with Heart Failure (MLHF) questionnaire. [ Time Frame: At 6 Month and 12 Month visit ]
    Evaluate Quality Of Life Changes via Minnesota Living with Heart Failure (MLHF) Questionnaire

  22. Incidence of Major Adverse Cardiac Events (MACE) [ Time Frame: At 6 Month and 12 Month visit ]
    Incidence of Major Adverse Cardiac Events (MACE), defined as the composite incidence of (1) death, (2) hospitalization for worsening HF, or (3) non-fatal recurrent MI.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   21 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • In order to participate in this study, a patient MUST:

    1. Be ≥ 21 and < 90 years of age.
    2. Provide written informed consent.
    3. Have a diagnosis of chronic ischemic left ventricular dysfunction secondary to myocardial infarction (MI) as defined by the following: Screening MRI must show an area of akinesis, dyskinesis, or severe hypokinesis associated with evidence of myocardial scarring based on delayed hyperenhancement following gadolinium infusion.
    4. Been treated with appropriate maximal medical therapy for heart failure or post-infarction left ventricular dysfunction. For beta-blockade, the patient must have been on a stable dose of a clinically appropriate beta-blocker for 3 months. For angiotensin-converting enzyme inhibition, the patient must have been on a stable dose of a clinically appropriate agent for 1 month.
    5. Be a candidate for cardiac catheterization.
    6. Have an ejection fraction ≤ 50% by gated blood pool scan, two-dimensional echocardiogram, cardiac MRI, or left ventriculogram within the prior six months and not in the setting of a recent ischemic event.

Exclusion Criteria:

  • In order to participate in this study, a patient MUST NOT:

    1. Have a baseline glomerular filtration rate < 50 ml/min1.73m2.
    2. Have a known, serious radiographic contrast allergy.
    3. Have a mechanical aortic valve or heart constrictive device.
    4. Have a documented presence of aortic stenosis (aortic stenosis graded as ≥ +2 equivalent to an orifice area of 1.5cm2 or less).
    5. Have a documented presence of moderate to severe aortic insufficiency (echocardiographic assessment of aortic insufficiency graded as ≥+2).
    6. Require coronary artery revascularization. Patients who require or undergo revascularization procedures should undergo these procedures a minimum of 3 months in advance of treatment within this study. In addition, patients who develop a need for revascularization following enrollment will be submitted for this therapy without delay.
    7. Evidence of a life-threatening arrhythmia (nonsustained ventricular tachycardia ≥ 20 consecutive beats or complete heart block) or QTc interval > 550 ms on screening ECG.
    8. AICD firing in the past 60 days prior to the procedure.
    9. Have unstable angina within 2 weeks of the planned procedure.
    10. Have a hematologic abnormality as evidenced by hematocrit < 25%, white blood cell < 2,500/ul or platelet values < 100,000/ul without another explanation.
    11. Have liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three times the ULN.
    12. Have a coagulopathy = (INR > 1.3) not due to a reversible cause (i.e., Coumadin). Patients on Coumadin will be withdrawn 5 days before the procedure and confirmed to have an INR < 1.3. Patients who cannot be withdrawn from Coumadin will be excluded from enrollment
    13. Have known allergies to penicillin or streptomycin.
    14. Have a contra-indication to performance of an MRI scan.
    15. Be an organ transplant recipient.
    16. Have a 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.
    17. Have a non-cardiac condition that limits lifespan to < 1 year.
    18. Have a history of drug or alcohol abuse within the past 24 months.
    19. Be on chronic therapy with immunosuppressant medication, such as corticosteroids or TNFα antagonists.
    20. Be serum positive for HIV, hepatitis BsAg or hepatitis C.
    21. Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.
    22. Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female patients must undergo a blood or urine pregnancy test at screening and within 36 hours prior to injection.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02503280


Contacts
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Contact: Joshua M Hare, MD 305-243-5579 Jhare@med.miami.edu
Contact: Study Coordinators 305-243-7444 ISCIStudyInfo@miami.edu

Locations
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United States, Florida
ISCI / University of Miami Not yet recruiting
Miami, Florida, United States, 33136
Contact: Joshua M Hare, MD    305-243-7444    ISCIStudyInfo@miami.edu   
Sponsors and Collaborators
Joshua M Hare
Investigators
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Principal Investigator: Joshua M Hare, MD ISCI / University of Miami Miller School of Medicine

Additional Information:
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Responsible Party: Joshua M Hare, ISCI Director, Chief Science Officer, Senior Assoc. Dean, Louis Lemberg Professor of Medicine, University of Miami
ClinicalTrials.gov Identifier: NCT02503280     History of Changes
Other Study ID Numbers: 20120203
First Posted: July 20, 2015    Key Record Dates
Last Update Posted: December 24, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Joshua M Hare, University of Miami:
Cardiovascular
Secondary

Additional relevant MeSH terms:
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Myocardial Infarction
Infarction
Pathologic Processes
Myocardial Ischemia
Heart Failure
Ventricular Dysfunction
Ventricular Dysfunction, Left
Ischemia
Heart Diseases
Cardiovascular Diseases
Necrosis
Vascular Diseases