Intramyocardial injection of autologous bone marrow mononuclear cells for patients with chronic ischemic heart disease and left ventricular dysfunction (First Mononuclear Cells injected in the US [FOCUS]): Rationale and design

Willerson, James T.; Perin, Emerson C.; Ellis, Stephen G.; Pepine, Carl J.; Henry, Timothy D.; Zhao, David X.M.; Lai, Dejian; Penn, Marc S.; Byrne, Barry J.; Silva, Guilherme; Gee, Adrian; Traverse, Jay H.; Hatzopoulos, Antonis K.; Forder, John R.; Martin, Daniel; Kronenberg, Marvin; Taylor, Doris A.; Cogle, Christopher R.; Baraniuk, Sarah; Westbrook, Lynette; Sayre, Shelly L.; Vojvodic, Rachel W.; Gordon, David J.; Skarlatos, Sonia I.; Moyé, Lemuel A.; Simari, Robert D.; for the Cardiovascular Cell Therapy Research Network (CCTRN),

doi:10.1016/j.ahj.2010.03.029

« Previous Next »American Heart Journal
Volume 160, Issue 2 , Pages 215-223, August 2010

Intramyocardial injection of autologous bone marrow mononuclear cells for patients with chronic ischemic heart disease and left ventricular dysfunction (First Mononuclear Cells injected in the US [FOCUS]): Rationale and design

James T. Willerson, MD
- Reprint requests: James T. Willerson, MD, University of Texas, School of Public Health, 1200 Herman Pressler, E801, Houston, TX 77030.
Emerson C. Perin, MD
Stephen G. Ellis, MD
Carl J. Pepine, MD
Timothy D. Henry, MD
David X.M. Zhao, MD
Dejian Lai, PhD
Marc S. Penn, MD, PhD
Barry J. Byrne, MD
Guilherme Silva, MD
Adrian Gee, MD
Jay H. Traverse, MD
Antonis K. Hatzopoulos, MD, PhD
John R. Forder, MD
Daniel Martin, MD
Marvin Kronenberg, MD
Doris A. Taylor, PhD
Christopher R. Cogle, MD
Sarah Baraniuk, PhD
Lynette Westbrook, RN
Shelly L. Sayre, MPH
Rachel W. Vojvodic, MPH
David J. Gordon, PhD
Sonia I. Skarlatos, PhD
Lemuel A. Moyé, MD, PhD
Robert D. Simari, MD
for the Cardiovascular Cell Therapy Research Network (CCTRN)

Coordinating Center for Clinical Trials, The University of Texas, Health Science Center, Houston, TX

Received 8 October 2009; accepted 16 March 2010.

Background

The increasing worldwide prevalence of coronary artery disease (CAD) continues to challenge the medical community. Management options include medical and revascularization therapy. Despite advances in these methods, CAD is a leading cause of recurrent ischemia and heart failure, posing significant morbidity and mortality risks along with increasing health costs in a large patient population worldwide.

Trial Design

The Cardiovascular Cell Therapy Research Network (CCTRN) was established by the National Institutes of Health to investigate the role of cell therapy in the treatment of chronic cardiovascular disease. FOCUS is a CCTRN-designed randomized, phase II, placebo-controlled clinical trial that will assess the effect of autologous bone marrow mononuclear cells delivered transendocardially to patients with left ventricular (LV) dysfunction and symptomatic heart failure or angina. All patients need to have limiting ischemia by reversible ischemia on single-photon emission computed tomography assessment.

Results

After thoughtful consideration of both statistical and clinical principles, we will recruit 87 patients (58 cell treated and 29 placebo) to receive either bone marrow–derived stem cells or placebo. Myocardial perfusion, LV contractile performance, and maximal oxygen consumption are the primary outcome measures.

Conclusions

The designed clinical trial will provide a sound assessment of the effect of autologous bone marrow mononuclear cells in improving blood flow and contractile function of the heart. The target population is patients with CAD and LV dysfunction with limiting angina or symptomatic heat failure. Patient safety is a central concern of the CCTRN, and patients will be followed for at least 5 years.