AMR-001

Overview

Status: Active, not recruiting
Keywords: Heart Faulure , Heart Stem Cell Therapy , Stem Cell , Ischemic Cardiomyopathy , Myocardial Infarct
IRB Number: 00057064
Specialty: Cardiology, Cardiology, Cardiothoracic Surgery, Cardiology, Cardiothoracic Surgery, Cardiothoracic Surgery
Sub Specialties: Interventional Cardiology, Coronary Revascularization, Heart Failure, Heart Stem Cell Therapy, Heart Failure

Brief Summary

Early clinical data demonstrates that following a myocardial infarction (MI or heart attack) the acute loss of myocardial muscle cells and the low perfusion of oxygenated blood to that general area of the heart results in damage to the heart.  The initial decrease in blood flow to the heart results in a series of events that leads to a decrease in cardiac function that can potentially exist long term.  Standard of care treatment including surgery, angioplasty and/or stent placement can minimize the adverse affects of the heart attack and improve blood flow.  However early research data has shown that cell therapy- in this study referred to as AMR-001, delivered during a specific window of time- which for this study is between day 4 -14 post MI, has shown that in addition to the standard of care treatment, the results from the stem cells' administration leads to neoangiogenesis which is the development of new blood vessels, thus leading to further improved blood flow to the damaged area of the heart and to cardiomyocyte (heart cells) preservation.   

In this trial the primary objective is:

1. To determine safety and the effect of intracoronary infusion of AMR-001 on myocardial perfusion to patients who have had a ST segment elevation myocardial infarction (STEMI) and received a stent. 

The secondary objectives of the study are:

1. To assess the effect of intra-coronary infusion of AMR-001 on MI size and cardiac function. Function will be assessed by measuring left ventricular ejection fraction (LVEF), end systolic and end diastolic volumes, regional myocardial strain and regional wall motion.

2. To assess Quality of Life meaures for change.

3.  Comparison of the difference in individual and cumulative MACE (defined as cardiac mortality, hospitalization for worsening heart failure, or recurrent AMI) collected at 6 months, one year, 18 months, two years and three years.

The tertiary objective is:

1. To assess the relationship between the quantity and quality of CD34+ cells infused and perfusion (RTSS), infarct size, LV function and clinical outcomes.

2. Correlate baseline LVEF, baseline infarct size, baseline RTSS score, number of prior AMI, IRA site and time to stent placement with changes in perfusion, infarct size, LV function and clinical outcomes.

 

Principal Investigator: Amit Patel
Department: Cardiothoracic Divison
Co Investigator: Anwar Tandar
Co Investigator: Rodney Badger

Contact Information

Name:Matthew Brobeck
Phone: 801.585.6743
Email: matthew.brobeck@hsc.utah.edu

Inclusion Criteria

 Inclusion Criteria:
1. Age 18 years or older.
2. Acute ST elevation myocardial infarction meeting ACC/AHA criteria, with symptoms of chest pain within 3 days of admission. Criteria include (ST elevation > 1mm in limb leads or 2 mm in two or more precordial leads, and increased levels of troponin, CPK MB or both).
3. Successful stent placement and reperfusion within 3 days of chest pain onset (as defined in exclusion criteria #1) and with TIMI Flow score of 2 or 3 and infarct related artery (IRA) with <20% stenosis after revascularization.
4. Wall motion abnormality associated with the target lesion
5. NYHA heart failure class I, II or III.
6. Study entry LVEF ≤48% determined by CMR no sooner than 96 hours from stent placement. For subjects with contraindications to magnetic resonance imaging, including implanted devices, study entry LVEF ≤45% determined by SPECT scan no sooner than 96 hours from stent placement.
7. Able to provide informed written consent and willing to participate in all required study follow-up assessments.
8. Subjects must have an INR ≤ 2.0 within 2 days of the bone marrow harvest collection.
9. Subjects must have a Hgb ≥ 10 grams/dL, WBC ≥ 3500 cells/mm3, a platelet count ≥ 100,000 cells/mm3, serum creatinine ≤ 2.5 mg/dL, and total bilirubin ≤ 2.0 mg/dL within 7 days of the bone marrow collection or by the end of screening phase.
10. Expected survival of at least one year.
11. Females of child bearing potential agree to use birth control (barrier method accepted) for one month post bone marrow harvest.
12. Post Randomization Criteria to Receive Infusion of Investigational Product: Seated systolic blood pressure of at least 90 mm Hg on the day of harvest, prior to initiating investigational procedures (and prior to administration of sedative agents).
If systolic blood pressure is less than 90 mm Hg and patient has changes in vital signs with orthostatic maneuvers or appears clinically hypovolemic, treatment with fluids must raise systolic blood pressure to at least 90 mm Hg prior to initiation of further investigational procedures. Patients with persistent systolic blood pressure of <90 mm Hg are not eligible to undergo harvest.

Exclusion Criteria

Exclusion Criteria:
1. Continuous/ongoing chest pain – unremitting and unresponsive to nitroglycerin or rest – persisting 4 or more days before stent placement. If the chest pain syndrome is transient and/or intermittent – even if it began more than 3 days prior to admission – the patient is not excluded.
2. Subjects in cardiogenic shock (systolic pressure < 80mm/Hg, on vasopressors or intra-aortic counterpulsation) at the time of consenting. Subjects who recover from cardiogenic shock by the time of consenting are eligible.
3. Subjects unable to receive antiplatelet agents (e.g. aspirin, clopidogrel, ticlopidine, prasugrel, etc).
4. Subjects receiving warfarin who have an INR >2 at the end of the screening phase or with major bleeding requiring active transfusion support.
5. Subjects who require continuous anticoagulation during the time when the bone marrow harvest is scheduled, as heparin must be discontinued for 4 hours prior to and 24 hours after bone marrow harvest procedure (Appendix VII).
6. Subjects with severe cardiac valvular disease expected to undergo surgery within 1 year.
7. Subjects with known severe immunodeficiency states (AIDS).
8. Cirrhosis requiring active medical management.
9. Malignancy requiring active treatment (except basal cell skin cancer).
10. Subjects with documented active alcohol and /or other substance abuse.
11. Females of child bearing potential unless a pregnancy test is negative within 7 days of the bone marrow harvest.
12. Re-occlusion of the infarct related artery (IRA) prior to the infusion procedure.
13. Planned revascularization intervention during the next 6 months. (A second PCI can be performed if done prior to qualifying CMR at least 96 hours post primary PCI).
14. Participation in an ongoing investigational trial.
15. Active or suspected bacterial infection requiring systemic intravenous antibiotics.

16. Post Randomization Criteria to Receive Infusion of Investigational Product: Bone marrow harvest should be terminated for patients who become sufficiently unstable that vasopressors(s) (or more aggressive therapy) is (are) required, and subject can continue to participate in trial only if the bone marrow harvested prior to the initiation of vasopressors proves sufficient .to manufacture AMR-001/placebo. Even when patients are stabilized and weaned from vasopressors, no further bone marrow can be harvested.