© 2010 by the Texas Heart ® Institute, Houston Volume 37, Number 4, 2010 412 Rationale and Design of LateTIME Trial LateTIME A Phase-II, Randomized, Double-Blinded, Placebo- Controlled, Pilot Trial Evaluating the Safety and Effect of Administration of Bone Marrow Mononuclear Cells 2 to 3 Weeks after Acute Myocardial Infarction A realistic goal for cardiac cell therapy may be to attenuate left ventricular remodeling fol- lowing acute myocardial infarction to prevent the development of congestive heart failure. Initial clinical trials of cell therapy have delivered cells 1 to 7 days after acute myocardial infarction. However, many patients at risk of developing congestive heart failure may not be ready for cell delivery at that time-point because of clinical instability or hospitalization at facilities without access to cell therapy. Experience with cell delivery 2 to 3 weeks after acute myocardial infarction has not to date been explored in a clinical trial. The objective of the LateTIME study is to evaluate by cardiac magnetic resonance the effect on global and regional left ventricular function, between baseline and 6 months, of a single intracoronary infusion of 150 × 10 6 autologous bone marrow mononuclear cells (compared with pla- cebo) when that infusion is administered 2 to 3 weeks after moderate-to-large acute myo- cardial infarction. The 5 clinical sites of the Cardiovascular Cell Therapy Research Network (CCTRN) will enroll a total of 87 eligible patients in a 2:1 bone marrow mononuclear cells- to-placebo patient ratio; these 87 will have undergone successful percutaneous coronary intervention of a major coronary artery and have left ventricular ejection fractions ≤0.45 by echocardiography. When the results become available, this study should provide insight into the clinical feasibility and appropriate timing of autologous cell therapy in high-risk patients after acute myocardial infarction and percutaneous coronary intervention. (Tex Heart Inst J 2010;37(4):412-20) F ollowing an acute myocardial infarction (AMI), there is replacement of myo- cytes by fibrotic tissue and ongoing apoptotic loss of viable cardiac myocytes in the infarct border zone as a result of reperfusion injury and ongoing isch- emia from microvascular obstruction. If the infarction is large, left ventricular (LV) dysfunction may develop due to scar expansion and LV dilation, ultimately leading to the development of congestive heart failure. Congestive heart failure is the leading admission diagnosis for hospitalization in the United States and carries a 5-year mor- tality rate of 50%. 1 Although medical therapy can improve symptoms and extend survival to a limited degree, cardiac transplantation remains the only curative pro- cedure available. Recent studies in animals with experimental AMI have observed significant recov- ery of LV function after the delivery of bone marrow–derived stem cells. 2-4 Although the mechanisms of benefit are subject to ongoing investigation, 5,6 the potential has led to the initiation of multiple clinical trials to test the concept that delivery of autol- ogous bone marrow mononuclear cells (BMMNCs) into the infarct region can im- prove cardiac function after AMI. 7-11 Several meta-analyses 12-14 have demonstrated that Clinical Investigation Jay H. Traverse, MD Timothy D. Henry, MD Douglas E. Vaughan, MD Stephen G. Ellis, MD Carl J. Pepine, MD James T. Willerson, MD David X.M. Zhao, MD Lara M. Simpson, PhD Marc S. Penn, MD, PhD Barry J. Byrne, MD Emerson C. Perin, MD, PhD Adrian P. Gee, MD Antonis K. Hatzopoulos, MD, PhD David H. McKenna, MD John R. Forder, MD Doris A. Taylor, PhD Christopher R. Cogle, MD Sarah Baraniuk, PhD Rachel E. Olson, RN Beth C. Jorgenson, 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) Key words: Apoptosis; bone marrow cells; bone marrow transplantation; cell therapy; colony-stimulating factors; free radicals; heart failure; infusions, intra-arteri- al; inflammation/prevention & control; magnetic reso- nance imaging; myocardial infarction/therapy; myocar- dial ischemia/therapy; myo- cardial reperfusion injury; myocytes, cardiac; prospec- tive studies; regeneration; research design; stem cells; stem cell transplantation; time factors; ventricular function, left; ventricular remodeling Address for reprints: Lemuel A. Moyé, MD, PhD, Department of Biostatistics, University of Texas School of Public Health, RAS Bldg., 1200 Herman Pressler, Houston, TX 77030 E-mail: Lemuel.A.Moye@ uth.tmc.edu From: Baylor University School of Medicine (Dr. Gee); The Cleveland Clinic Foundation (Drs. Ellis and Penn); Mayo Clinic (Dr. Simari); Minneapolis Heart Institute at Abbott Northwestern Hospital (Drs. Henry and Traverse, and Mss Jorgenson and Olson); National Heart, Lung and Blood Institute (Drs. Gordon and Skarlatos); Texas Heart Institute at St. Luke’s Episcopal Hospital (Drs. Perin and Willerson); University of Florida School of Medicine (Drs. Byrne, Cogle, Forder, and Pepine); Uni- versity of Minnesota School of Medicine (Drs. Henry, McKenna, Taylor, and Traverse); University of Texas School of Public Health (Drs. Baraniuk, Moyé, and Simpson, and Mss Sayre and Vojvodic); Vanderbilt University School of Medicine (Drs. Hatzopoulos, Vaughan, and Zhao) This study is supported by the NHLBI (U01 HL087318-01) and by the Production Assistance for Cellular Therapies (PACT), N01-HB-37164. The percutaneous transluminal coronary angioplasty and guide catheters and wires were generously supplied by Boston Scientific Corporation (Natick, Mass). ClinicalTrials.gov #NCT00684021.