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

Joshua M Hare

Status and phase: Withdrawn; Phase 2; Phase 1

Conditions: Chronic Ischemic Left Ventricular Dysfunction; Myocardial Infarction

Treatments: Drug: Autologous hMSCs; Device: Biosense Webster MyoStar NOGA Injection Catheter System; Drug: Placebo; Drug: Autologous Human C-Kit CSCs II

Study type: Interventional

Funder types: Other

Identifiers

NCT02503280

20120203

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 21 to 89 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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0 participants in 3 patient groups, including a placebo group

Group A - Autologous hMSCs

Experimental group

Description:

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.

Treatment:

Drug: Autologous hMSCs

Device: Biosense Webster MyoStar NOGA Injection Catheter System

Group B - Autologous Human C-Kit CSCs II

Experimental group

Description:

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.

Treatment:

Drug: Autologous Human C-Kit CSCs II

Device: Biosense Webster MyoStar NOGA Injection Catheter System

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Device: Biosense Webster MyoStar NOGA Injection Catheter System