[TCT2007]SEACOAST: Direct Coronary Delivery of Stem Cells Safe at Six Months

First clinical trial in the United States to evaluate direct coronary delivery of CD133+ cells; phase 2 study planned.
No cardiac events were seen at 6 months in a phase 1 study of direct coronary delivery of autologous stem cells in patients with total coronary artery occlusions.

Vincent J. Pompili, MD, discussed the midpoint results of the 1-year SEACOAST (Safety and Efficacy of Autologous Intracoronary Stem Cell Injections in Total Coronary Artery Occlusions) trial.

In nine patients (mean age, 65), all safety endpoints were met, Pompili said. With infusion of up to 3 million cells, there were no docu¬mented adverse events, myocardial infarcts, or arrhythmias. There was also no elevation of cardiac markers.

In addition, there was a reversal of perfusion defects in six of nine pa¬tients, with an improvement in one or more grades of ischemia (Figure).

Dose-escalation study

SEACOAST was a single-cen¬ter, phase 1 dose-escalation study of autologous stem cell therapy in patients with total coronary artery occlusion. Eligible patients had one region of chronically ischemic myocardium that was 100% occluded and could not be treated using conventional PCI. Patients also had to have well-established collateral vessels, at least 1.5 mm in luminal diameter, to the ischemic area and evidence of viable myocardium in the area demonstrated by nuclear imaging. Other inclusion criteria were LVEF greater than 45% on echocardiogram and class II to IV angina per the Canadian Cardiovascular Society definition.

Approximately 200 mL of bone marrow was aspirated from each patient, and CD133+ cells were isolated from the aspirate and purified. The autologous cells were then infused via catheter into the collateral vessels supplying the occluded area. Three doses of the CD133+ cells were evaluated: 1 million, 2 million, and 3 million cells.

No adverse events were noted during the harvesting or infusion of the autologous cells.

Future studies

In addition to the 6-month safety results, Pompili spoke about correlative studies now under way and fu¬ture directions for research related to SEACOAST.

He and colleagues at Case Western Reserve University are investigating whether differences in the function of endothelial progenitor cells can be overcome by augment¬ing the cell dose. They also are exploring whether genetic modification of autologous EPCs can increase their functionality.

The researchers have used a nano¬fiber matrix to expand cells 250-fold without driving them toward differentiation. After reculturing, these expanded cells can then be driven to differentiation.

The SEACOAST II trial, to be¬gin in 2008, will continue the investigation of autologous CD133+ stem cells in 96 patients. This randomized single-center trial will evaluate safety endpoints and the primary efficacy endpoints of improvement in treadmill and angina scores.
Vincent J. Pompili, MD