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

Myocardial Infarction Clinical Trial

— TAC-HFT-II  

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.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02503280
• Other study ID #: 20120203
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: March 1, 2025
• Est. completion date: March 2032

Study information

• Verified date: October 2020
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2032
• Est. primary completion date: March 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 89 Years

Eligibility

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 TNFa 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.

Related Conditions & MeSH terms

• Chronic Ischemic Left Ventricular Dysfunction
• Heart Failure
• Infarction
• Ischemia
• Myocardial Infarction
• Ventricular Dysfunction
• Ventricular Dysfunction, Left

Intervention

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.
• 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.
• 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

Locations

Country	Name	City	State
United States	ISCI / University of Miami	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Joshua M Hare

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of any treatment emergent serious adverse events (TE-SAEs)	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.	One Month post-catheterization
Secondary	Treatment Emergent adverse event rates	Rate of adverse events occurring ad	At 6 Month and 12 Month visit
Secondary	Ectopic tissue formation	Ectopic tissue formation (as identified from MRI scans of the chest, abdomen, & pelvis).	At 6 Month and 12 Month visit
Secondary	48-hour ambulatory electrocardiogram (ECG) recordings.	Electrocardiogram (ECG) recordings measured over 48 Hours	At 6 Month and 12 Month visit
Secondary	Hematology value changes post-catheterization	Hematology value changes will be observed at the 6 month and 12 month visit post-catheterization.	At 6 Month and 12 Month visit
Secondary	Urinalysis results changes post-catheterization	Urinalysis results changes will be observed at the 6 month and 12 month visit post-catheterization.	At 6 Month and 12 Month visit
Secondary	Clinical chemistry values post-catheterization	Clinical chemistry value changes will be observed at the 6 month and 12 month visit post-catheterization.	At 6 Month and 12 Month visit
Secondary	Pulmonary function	Pulmonary function - forced expiratory volume in 1 second (FEV1) results.	At 6 Month and 12 Month visit
Secondary	Serial troponin I values	Serial troponin I values (every 12 hours for first 48 hours post-cardiac catheterization).	Every 12 hours for the first 48 hours post-cardiac catheterization
Secondary	Creatine kinase-MB (CK-MB) value changes post-catheterization	CK-MB values (every 12 hours for first 48 hours post-cardiac catheterization).	Every 12 hours for first 48 hours post-cardiac catheterization
Secondary	Post-cardiac catheterization echocardiogram.	Echocardiogram performed after cardiac catheterization	Day 1 Post Echocardiogram
Secondary	Magnetic resonance imaging (MRI) measures of infarct scar size (ISS)	Document Infarct Scar Size (ISS) via Magnetic Resonance imaging (MRI)	At 6 Month and 12 Month visit
Secondary	Echocardiographic measures of infarct scar size (ISS)	Document Infarct Scar Size (ISS) via echocardiographic procedure	At 6 Month and 12 Month visit
Secondary	Magnetic resonance imaging (MRI) of Left Regional Ventricular Function	Document Left Regional Ventricular Function via Magnetic Resonance imaging (MRI)	At 6 Month and 12 Month visit
Secondary	Echocardiographic measures of Left Regional Ventricular Function	Document Left Regional Ventricular Function via echocardiographic procedure	At 6 Month and 12 Month visit
Secondary	Magnetic resonance imaging (MRI) of Global Ventricular Function	Document Global Ventricular Function via Magnetic Resonance imaging (MRI)	At 6 Month and 12 Month visit
Secondary	Echocardiographic measures of Global Ventricular Function	Document Global Ventricular Function via echocardiographic procedure	At 6 Month and 12 Month visit
Secondary	Tissue perfusion measured by MRI.	Measure Tissue Perfusion via Magnetic Resonance imaging (MRI)	At 6 Month and 12 Month visit
Secondary	Peak oxygen consumption (Peak VO2) (by treadmill determination).	Peak VO2 Oxygen Consumption determined by utilizing treadmill	At 6 Month and 12 Month visit
Secondary	Six-minute walk test.	Evaluate Functional Capacity via the Six Minute Walk Test	At 6 Month and 12 Month visit
Secondary	New York Heart Association (NYHA) functional class.	Evaluate Functional Capacity via New York Heart Association (NYHA) Class Determination	At 6 Month and 12 Month visit
Secondary	Minnesota Living with Heart Failure (MLHF) questionnaire.	Evaluate Quality Of Life Changes via Minnesota Living with Heart Failure (MLHF) Questionnaire	At 6 Month and 12 Month visit
Secondary	Incidence of Major Adverse Cardiac Events (MACE)	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.	At 6 Month and 12 Month visit

External Links

•   Interdisciplinary Stem Cell Institute at the University of Miami Miller School of Medicine