Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS)

• Incidence of serious adverse events (SAEs), defined as the 6-month post-CABG surgery SAE proportion of patients experiencing sustained ventricular arrhythmias, ectopic tissue formation, or sudden unexpected death [ Time Frame: Measured at Month 6 after surgery ] [ Designated as safety issue: Yes ]
  

• MRI and echocardiographic measures of Infarct Scar Size (ISS) and left regional and global ventricular function [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ] [ Designated as safety issue: No ]
  
• Treatment emergent adverse event rates [ Time Frame: Measured over the 6-month follow-up period, at Month 12 follow-up and at Month 18 follow-up ] [ Designated as safety issue: Yes ]
  
• 48-hour ambulatory electrocardiogram (ECG) recordings [ Time Frame: Measured over the 6-month follow-up period, at Month 12 follow-up and at Month 18 follow-up ] [ Designated as safety issue: Yes ]
  
• Hematology, clinical chemistry, and urinalysis values [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ] [ Designated as safety issue: Yes ]
  
• Pulmonary function - forced expiratory volume in 1 second (FEV1) results [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ] [ Designated as safety issue: Yes ]
  
• Cardiac computed tomography measures of ISS, left ventricular ejection fraction, and end diastolic and end systolic volumes [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ] [ Designated as safety issue: No ]
  
• Serial troponin and creatine kinase MB (CK-MB) values [ Time Frame: Measured every 12 hours for the first 48 hours after surgery ] [ Designated as safety issue: Yes ]
  
• Peak VO2 (by treadmill determination) and 6-minute walk test [ Time Frame: Measured at baseline and Months 6 and 18 follow-ups ] [ Designated as safety issue: No ]
  
• New York Heart Association (NYHA) functional class [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ] [ Designated as safety issue: No ]
  
• Minnesota Living with Heart Failure (MLHF) questionnaire [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ] [ Designated as safety issue: No ]
  
• Incidence of the Major Adverse Cardiac Events (MACE) endpoint, defined as the composite incidence of (1) death, (2) hospitalization for heart failure, or (3) non-fatal recurrent heart attack [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ] [ Designated as safety issue: No ]
  

Participation in this study will last 18 months. Potential participants will undergo initial screening 5 to 7 weeks prior to CABG surgery. Screening will include a physical exam, blood draw, pregnancy test, questions about medical history, current medications, and alcohol or drug use, an electrocardiogram (ECG), magnetic resonance imaging (MRI) of the heart, questionnaires, an echocardiogram and a computed tomography (CT) scan. Eligible participants will then undergo two baseline visits within 6 weeks of their scheduled surgery. Baseline Visit 1 will consist of vital sign measurements, a bone marrow aspiration to obtain MSCs and a blood draw for a biomarker test. Baseline Visit 2 will include treadmill test, 6-minute walk test, pulmonary function (FEV1) study and a 48 Hour Ambulatory ECG. After the second baseline visit, participants will be assigned randomly to receive either MSCs or placebo after surgery.

On the day of surgery, once all of the bypass grafts have been placed, a high or low dose of MSCs or placebo will be injected into a damaged area of the heart that did not receive a bypass graft. After receiving the injections, participants will remain in the hospital for up to 7 days. During this stay, participants will undergo a daily blood draw, urine test, ECG, and ambulatory ECG monitoring for the first 96 hours after surgery.

Upon being discharged, participants will return for monthly visits for 6 months and for follow-up visits 12 and 18 months after surgery. These visits will repeat most initial screening and baseline tests. There will be one additional visit 14 days after surgery, which will include questions about side effects, a physical exam, and a 48-hour ambulatory ECG.