NBS10 (Also Known as AMR-001) Versus Placebo Post ST Segment Elevation Myocardial Infarction

Efficacy endpoint is at 6 months. Clinical endpoints and safety will be measured through 36 months.

Inclusion criteria

• Age 18 years or older.
• 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).

Chest pain syndrome can extend to more than 3 days prior to admission if its course is consistent with transient/intermittent ischemia rather than symptoms that are continuous suggesting ongoing infarction extending beyond 3 days.

• Successful stent placement and reperfusion within 3 days of chest pain onset and with TIMI Flow score of 2 or 3 and infarct related artery (IRA) with <20% stenosis after revascularization.
• Wall motion abnormality associated with the target lesion
• NYHA heart failure class I, II or III.
• Study entry LVEF <48% determined by CMR no sooner than 96 hours from stent placement.
• Able to provide informed written consent and willing to participate in all required study follow-up assessments.
• Subjects must have an INR ≤ 2.0 within 2 days of the bone marrow collection.
• Subjects must have a Hgb ≥ 10 grams/dL, WBC ≥ 3500 cells/mm3, a platelet count ≥ 100,000 cells/mm3, serum creatinine ≤ 2.5, and total bilirubin ≤ 2.0 within 7 days of the bone marrow collection or by end of screening phase.
• Expected survival of at least one year.
• Females of child bearing potential agree to use birth control (barrier method accepted) for one month post bone marrow harvest.

Exclusion criteria

• 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.
• 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.
• Subjects unable to receive antiplatelet agents (e.g. aspirin, clopidogrel, ticlopidine, prasugrel, etc).
• Subjects receiving warfarin who have an INR >2 or with major bleeding requiring active transfusion support.
• 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. (See Appendix VII.)
• Subjects with severe cardiac valvular disease expected to undergo surgery within 1 year.
• Subjects with known severe immunodeficiency states (AIDS).
• Cirrhosis requiring active medical management.
• Malignancy requiring active treatment (except basal cell skin cancer).
• Subjects with documented active alcohol and /or other substance abuse.
• Females of child bearing potential unless a pregnancy test is negative within 7 days of the mini-bone marrow harvest.
• Re-occlusion of the IRA prior to the infusion procedure.
• 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).
• Participation in an ongoing investigational trial.
• Active or suspected bacterial infection requiring systemic intravenous antibiotics.