Randomized Evaluation of Intracoronary Transplantation of Bone Marrow Stem Cells in Myocardial Infarction

The main objective of this study is to investigate the safety and clinical outcome of
intracoronary infusion of autologous bone marrow cells in patients with myocardial
infarction (MI). We hypothesize that patients treated with stem cell therapy will have
beneficial effects on left ventricular (LV) remodeling and functional regeneration after MI
and successful primary percutaneous coronary intervention (PCI) in setting of prospective
randomized controlled trial.

Congestive heart failure (CHF), which is most commonly caused by acute myocardial infarction
(AMI), is the most frequent cause of hospitalization in the United States in patients over
the age of 65. Although current pharmacotherapy can inhibit neurohormonal activation, this
falls short in preventing LV remodeling and the development of CHF. Stem cells are
undifferentiated pluripotent cells that can be obtained from the patient and have the
potential to proliferate and differentiation into cardiomyocytes. The majority of the data
on stem cell transplantation comes from preclinical animal studies. Although the results are
interesting and perhaps safe, early phase I clinical studies are small and are very
preliminary. Data from large, randomized controlled trials are needed to clarify the short
and long term effects of cellular cardiomyoplasty.

Inclusion Criteria:

- Patients with acute myocardial infarction (ST elevation in at least 2 leads ≥ 0.2 mV
in V1,V2 or V3 or ≥ 0.1 mV in other leads), treated by one of the following
procedures:

- Acute PCI with stent implantation for acute ST elevation MI for either denovo
lesions or in-stent thrombosis

- Treatment with thrombolysis followed by PCI with stent implantation.

- Acute PCI / stent implantation has been successful (residual stenosis visually < 30%
and TIMI flow ≥ 2).

- At the time of inclusion (≥ 1 day post PCI) patient does no longer require i.v.
catecholamines or mechanical hemodynamic support (aortic balloon pump)

- Significant regional wall motion abnormality on echocardiography at the time of acute
PCI (ejection fraction ≤ 50% on visual estimation).

- Maximal cardiac troponin elevation ≥ 4 (measured at 37° C)

- Age 18 - 80 Years

- Written informed consent

Exclusion Criteria:

- Regional wall motion abnormality outside the area involved in the index acute
myocardial infarction.

- Need to acutely revascularize additional vessels, outside the infarct artery.

- Arteriovenous malformations or aneurysms

- Active infection or fever or diarrhea within last 4 weeks.

- Chronic inflammatory disease

- HIV infection or active hepatitis

- Neoplastic disease without documented remission within the past 5 years.

- Cerebrovascular insult within 3 months

- Impaired renal function (creatinine > 2 mg/dl) at the time of cell therapy

- Significant liver disease (GOT > 2x upper limit) or spontaneous INR > 1.5)

- Anemia (hemoglobin < 8.5 g/dl)

- Platelet count < 100,000/µl

- Hypersplenism

- History of bleeding disorder

- Gastrointestinal bleeding within 3 months

- Major surgical procedure or trauma within 2 months

- Uncontrolled hypertension

- Pregnancy

- Mental retardation

- Previously performed stem / mononuclear cell therapy

- Participation in another clinical trial within the last 30 days