Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS) (PROMETHEUS)
|Stem Cell Transplantation Ventricular Dysfunction, Left||Genetic: Lower dose mesenchymal stem cell (MSC) injection Genetic: Placebo Genetic: Higher dose MSC injection||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||A Phase I/II, Randomized, Double-Blinded, Placebo-Controlled Study of the Safety and Efficacy of Intramyocardial Injection of Autologous Human Mesenchymal Stem Cells (MSCs) in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction (MI) Undergoing Cardiac Surgery for Coronary Artery Bypass Grafting (CABG)|
- Incidence of Serious Adverse Events (SAEs) [ Time Frame: Measured at Month 6 after surgery ]Incidence of serious adverse events (SAEs), defined as the 6-month post-cardiac surgery for coronary artery bypss grafting CABG SAE proportion of patients experiencing sustained ventricular arrhythmias, ectopic tissue formation, or sudden unexpected death
- 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 ]
- 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 ]
- 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 ]
- Hematology, Clinical Chemistry, and Urinalysis Values [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ]
- 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 ]
- 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 ]
- Serial Troponin and Creatine Kinase MB (CK-MB) Values [ Time Frame: Measured every 12 hours for the first 48 hours after surgery ]
- Peak VO2 (by Treadmill Determination) and 6-minute Walk Test [ Time Frame: Measured at baseline and Months 6 and 18 follow-ups ]
- New York Heart Association (NYHA) Functional Class [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ]
- Minnesota Living With Heart Failure (MLHF) Questionnaire [ Time Frame: Measured over the 6-month follow-up period and at Month 18 follow-up ]
- 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 ]
|Study Start Date:||November 2007|
|Study Completion Date:||June 2011|
|Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
Experimental: (1) Lower MSC dose
Participants will receive lower dose mesenchymal stem cell injections for a total of 2 x 107 cells
Genetic: Lower dose mesenchymal stem cell (MSC) injection
Participants will receive between 10 and 20 intramyocardial injections of 2 million MSCs per 0.25-0.5 cubic centimeter (cc) for a total of 2 x 107 cells. The injections will be administered following completion of CABG surgery.
Experimental: (2) Higher MSC dose
Participants will receive higher dose of mesenchymal stem cell injections for a total of 2 x 108 cells
Genetic: Higher dose MSC injection
Participants will receive between 10 and 20 intramyocardial injections of 20 million MSCs per 0.25-0.5 cc for a total of 2 x 108 cells. The injections will be administered following completion of CABG surgery.
Placebo Comparator: (3) Placebo
Participants will receive placebo injections
Participants will receive between 10 and 20 placebo injections that consist of phosphate buffered saline (PBS) and 1% human serum albumin (HSA).
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00587990
|United States, Florida|
|University of Miami Miller School of Medicine|
|Miami, Florida, United States, 33136|
|United States, Maryland|
|Johns Hopkins University School of Medicine|
|Baltimore, Maryland, United States, 21205|
|Principal Investigator:||Joshua M. Hare, MD||University of Miami|
|Principal Investigator:||Alan W. Heldman, MD||University of Miami|
|Principal Investigator:||Gary Gerstenblith, MD||Johns Hopkins University|
|Principal Investigator:||John V. Conte, MD||Johns Hopkins University|
|Principal Investigator:||Steven P. Schulman, MD||Johns Hopkins University|