The TIME Randomized Trial:    Effect of Timing of Intracoronary  Delivery of Autologous Bone Marrow  Mononuclear Cells on ...
Organizational Structure: NHLBI       Cardiovascular Cell Therapy Research Network (CCTRN)                                ...
Rationale for TIME• Optimal timing for cell delivery post-AMI is unknown  and has not been directly tested in a prospectiv...
TIME Study Design• Study Aim: assess the effect of autologous BMCs and timing  of delivery at Day3 vs. Day7 post MI on mea...
Cell Processing                          •   Local, automated                          •   Sepax System                   ...
Baseline Characteristics                           6
Infarct Size and Treatment Times                                   3 Days                                     BMC         ...
Cell Characteristics                       8
Primary Endpoint: GlobalNo differencein the changein LVEFbetween BMC(n=75) andPlacebo (n=37)groups frombaseline to 6months...
Effect of Delivery Timing on the Change from            Baseline to Six Months for LVEFResults for both infarct zone and b...
Primary Endpoint: RegionalNo difference in the change of regional wall motion in the infarct        and border zone betwee...
Secondary Endpoints:Infarct Size and LV Volumes                              12
Clinical/Safety Outcomesat 6-month Endpoint Window                              13
Conclusions• Intracoronary delivery of autologous BMCs 3 or 7  days following primary PCI + stenting after  moderate to la...
Acknowledgements•   National Heart Lung & Blood Institute•   Biosafe•   Boston Scientific•   The clinical centers (Clevela...
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The Effect of Timing of Stem Cell Delivery Following Acute Myocardial Infarction: The NHLBI and CCTRN TIME Trial

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SOLACI Coverage: AHA 2012 Congress. Dr. Jay H. Traverse. Estudio TIME: Uso y duración de la infusión de células madre derivadas de médula ósea en la disfunción ventricular izquierda después de un infarto de miocardio.Find more presentations on our web http://solaci.org/es/aha_2012.php

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The Effect of Timing of Stem Cell Delivery Following Acute Myocardial Infarction: The NHLBI and CCTRN TIME Trial

  1. 1. The TIME Randomized Trial: Effect of Timing of Intracoronary Delivery of Autologous Bone Marrow Mononuclear Cells on Left Ventricular Function Following STEMI Jay H. Traverse, MD Principal Investigator, TIME StudyMinneapolis Heart Institute at Abbott Northwestern Hospital University of Minnesota Medical School Cardiovascular Cell Therapy Research Network (CCTRN) 2012 Scientific Sessions of the AHA
  2. 2. Organizational Structure: NHLBI Cardiovascular Cell Therapy Research Network (CCTRN) NHLBI Skarlatos PRC Chair DSMB Simari PDC Steering Committee P&P Data Coordinating Center Cell UTSPH Biorepository, cMRI, Echo, MVO2, SPECT Processing QC Lab Moyé Core Labs Skills Skills Development Development Core CoreTexas Heart Cleveland Minneapolis Vanderbilt U Florida Institute Clinic Heart Institute University Pepine Willerson Ellis Henry ZhaoCell Processing Cell Processing Cell Processing Cell Processing Cell Processing Satellites: Satellites: Satellites: Pepin Heart Institute University Hospitals United Heart & Vascular Clinic Metro Cardiology Consultants UMN 2 Mayo Clinic
  3. 3. Rationale for TIME• Optimal timing for cell delivery post-AMI is unknown and has not been directly tested in a prospective clinical trial.• Biochemical and structural changes in myocardium and bone marrow in first week (cytokines, inflammation, ROS) may create optimal window for cell delivery.• Almost all BMC trials delivered cells ≤7 days post-AMI. o REPAIR-AMI subgroup suggested later delivery preferable to earlier• LateTIME showed no benefit when BMCs delivered 2-3 weeks post-MI. 3
  4. 4. TIME Study Design• Study Aim: assess the effect of autologous BMCs and timing of delivery at Day3 vs. Day7 post MI on measures of LV function• Target Population: 120 patients w/first anterior MI, reperfused by PCI + stent, with residual LV dysfunction (EF≤45%)• Treatment: 150 x 106 autologous BMCs or placebo delivered by intracoronary infusion (Stop Flow)• Primary Endpoints: change in global and regional LV function from baseline to 6 months by cardiac MRI• Secondary Endpoints: change in infarct size and LV volumes• Subgroups: age, LVEF 4
  5. 5. Cell Processing • Local, automated • Sepax System – Automated processing – Includes cell washing – Closed system – Sterile disposable set • Validated by extensive pre-clinical testing Sepax vs. Manual Ficoll BMC • No difference in cell recovery, Ficoll migration or CFU ability • Equivalent perfusion in hindlimb ischemia modelManual Sepax 5
  6. 6. Baseline Characteristics 6
  7. 7. Infarct Size and Treatment Times 3 Days BMC (N=43) Placebo (N=24) 7 Days BMC (N=36) Placebo (N=17) 7
  8. 8. Cell Characteristics 8
  9. 9. Primary Endpoint: GlobalNo differencein the changein LVEFbetween BMC(n=75) andPlacebo (n=37)groups frombaseline to 6months 9
  10. 10. Effect of Delivery Timing on the Change from Baseline to Six Months for LVEFResults for both infarct zone and border zone wall motion were also notsignificant by therapy group for 3 days, 7 days, or overall. 10
  11. 11. Primary Endpoint: RegionalNo difference in the change of regional wall motion in the infarct and border zone between baseline and 6 months 11
  12. 12. Secondary Endpoints:Infarct Size and LV Volumes 12
  13. 13. Clinical/Safety Outcomesat 6-month Endpoint Window 13
  14. 14. Conclusions• Intracoronary delivery of autologous BMCs 3 or 7 days following primary PCI + stenting after moderate to large acute MIs is safe.• No improvement in global and regional LV function is observed at 6 months by cMRI in response to intracoronary BMC delivery.• Young patients at Day 7 randomized to BMCs had significant improvement with LVEF compared with placebo. 14
  15. 15. Acknowledgements• National Heart Lung & Blood Institute• Biosafe• Boston Scientific• The clinical centers (Cleveland Clinic, Minneapolis Heart Institute, Texas Heart Institute, University of Florida, and Vanderbilt University), their satellites (University Hospitals, United Heart & Vascular Clinic, Metropolitan Cardiology Consultants, University of Minnesota, Mayo Clinic, DeBakey VA, and Pepin Heart Institute) and their research teams• University of Texas School of Public Health• Center for Cell & Gene Therapy, Baylor College of Medicine• The University of Florida cMRI and Cleveland Clinic Echo Core Labs• The University of Minnesota and University of Florida Biorepositories• Simari Lab, Mayo Clinic 15

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