title: 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.
abstract: 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.
authors.affiliation: Coordinating Center for Clinical Trials, The University of Texas, Health Science Center, Houston, TX 77030, USA. jwillerson@sleh.com
authors.forename: James T
authors.initials: JT
authors.lastname: Willerson
authors.forename: Emerson C
authors.initials: EC
authors.lastname: Perin
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ellis
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Pepine
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Henry
authors.forename: David X M
authors.initials: DX
authors.lastname: Zhao
authors.forename: Dejian
authors.initials: D
authors.lastname: Lai
authors.forename: Marc S
authors.initials: MS
authors.lastname: Penn
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Byrne
authors.forename: Guilherme
authors.initials: G
authors.lastname: Silva
authors.forename: Adrian
authors.initials: A
authors.lastname: Gee
authors.forename: Jay H
authors.initials: JH
authors.lastname: Traverse
authors.forename: Antonis K
authors.initials: AK
authors.lastname: Hatzopoulos
authors.forename: John R
authors.initials: JR
authors.lastname: Forder
authors.forename: Daniel
authors.initials: D
authors.lastname: Martin
authors.forename: Marvin
authors.initials: M
authors.lastname: Kronenberg
authors.forename: Doris A
authors.initials: DA
authors.lastname: Taylor
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Cogle
authors.forename: Sarah
authors.initials: S
authors.lastname: Baraniuk
authors.forename: Lynette
authors.initials: L
authors.lastname: Westbrook
authors.forename: Shelly L
authors.initials: SL
authors.lastname: Sayre
authors.forename: Rachel W
authors.initials: RW
authors.lastname: Vojvodic
authors.forename: David J
authors.initials: DJ
authors.lastname: Gordon
authors.forename: Sonia I
authors.initials: SI
authors.lastname: Skarlatos
authors.forename: Lemuel A
authors.initials: LA
authors.lastname: Moyé
authors.forename: Robert D
authors.initials: RD
authors.lastname: Simari
mesh_terms: 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*