Clinical trial NCT02503280: The Transendocardial Autologous Cells (hMSC) or (hMSC) and (hCSC) in Ischemic Heart Failure Trial.
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.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Chronic Ischemic Left Ventricular Dysfunction
Myocardial Infarction
Keywords: Cardiovascular
Secondary
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2015-07-20
Enrollment: 0
Sex: ALL
Minimum age (years): 21
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Incidence of any treatment emergent serious adverse events (TE-SAEs)
timeFrame: One Month post-catheterization
Secondary outcomes:
measure: Treatment Emergent adverse event rates
timeFrame: At 6 Month and 12 Month visit
measure: Ectopic tissue formation
timeFrame: At 6 Month and 12 Month visit
measure: 48-hour ambulatory electrocardiogram (ECG) recordings.
timeFrame: At 6 Month and 12 Month visit
measure: Hematology value changes post-catheterization
timeFrame: At 6 Month and 12 Month visit
measure: Urinalysis results changes post-catheterization
timeFrame: At 6 Month and 12 Month visit
measure: Clinical chemistry values post-catheterization
timeFrame: At 6 Month and 12 Month visit
measure: Pulmonary function
timeFrame: At 6 Month and 12 Month visit
measure: Serial troponin I values
timeFrame: Every 12 hours for the first 48 hours post-cardiac catheterization
measure: Creatine kinase-MB (CK-MB) value changes post-catheterization
timeFrame: Every 12 hours for first 48 hours post-cardiac catheterization
measure: Post-cardiac catheterization echocardiogram.
timeFrame: Day 1 Post Echocardiogram
measure: Magnetic resonance imaging (MRI) measures of infarct scar size (ISS)
timeFrame: At 6 Month and 12 Month visit
measure: Echocardiographic measures of infarct scar size (ISS)
timeFrame: At 6 Month and 12 Month visit
measure: Magnetic resonance imaging (MRI) of Left Regional Ventricular Function
timeFrame: At 6 Month and 12 Month visit
measure: Echocardiographic measures of Left Regional Ventricular Function
timeFrame: At 6 Month and 12 Month visit
measure: Magnetic resonance imaging (MRI) of Global Ventricular Function
timeFrame: At 6 Month and 12 Month visit
measure: Echocardiographic measures of Global Ventricular Function
timeFrame: At 6 Month and 12 Month visit
measure: Tissue perfusion measured by MRI.
timeFrame: At 6 Month and 12 Month visit
measure: Peak oxygen consumption (Peak VO2) (by treadmill determination).
timeFrame: At 6 Month and 12 Month visit
measure: Six-minute walk test.
timeFrame: At 6 Month and 12 Month visit
measure: New York Heart Association (NYHA) functional class.
timeFrame: At 6 Month and 12 Month visit
measure: Minnesota Living with Heart Failure (MLHF) questionnaire.
timeFrame: At 6 Month and 12 Month visit
measure: Incidence of Major Adverse Cardiac Events (MACE)
timeFrame: At 6 Month and 12 Month visit
Other outcomes:
Locations:
city: Miami
country: United States
facility: ISCI / University of Miami
state: Florida
Study officials:
affiliation: ISCI / University of Miami Miller School of Medicine
name: Joshua M Hare, MD
role: PRINCIPAL_INVESTIGATOR
References: