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.
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.


METHODS
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.
Willerson
James T
JT
Coordinating Center for Clinical Trials, The University of Texas, Health Science Center, Houston, TX 77030, USA. jwillerson@sleh.com
Perin
Emerson C
EC
Ellis
Stephen G
SG
Pepine
Carl J
CJ
Henry
Timothy D
TD
Zhao
David X M
DX
Lai
Dejian
D
Penn
Marc S
MS
Byrne
Barry J
BJ
Silva
Guilherme
G
Gee
Adrian
A
Traverse
Jay H
JH
Hatzopoulos
Antonis K
AK
Forder
John R
JR
Martin
Daniel
D
Kronenberg
Marvin
M
Taylor
Doris A
DA
Cogle
Christopher R
CR
Baraniuk
Sarah
S
Westbrook
Lynette
L
Sayre
Shelly L
SL
Vojvodic
Rachel W
RW
Gordon
David J
DJ
Skarlatos
Sonia I
SI
Moyé
Lemuel A
LA
Simari
Robert D
RD
D016026:Bone Marrow Transplantation; D002908:Chronic Disease; D006801:Humans; D015552:Injections, Intralesional; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D016014:Linear Models; D017202:Myocardial Ischemia / Q000628:therapy*; D017063:Outcome Assessment, Health Care; D012107:Research Design; D015899:Tomography, Emission-Computed, Single-Photon; D014182:Transplantation, Autologous; D018487:Ventricular Dysfunction, Left / Q000628:therapy*