jay h. traverse, md principal investigator, time study minneapolis heart institute at abbott...
TRANSCRIPT
![Page 1: Jay H. Traverse, MD Principal Investigator, TIME Study Minneapolis Heart Institute at Abbott Northwestern Hospital University of Minnesota Medical School](https://reader030.vdocuments.us/reader030/viewer/2022032722/56649ced5503460f949ba726/html5/thumbnails/1.jpg)
Jay H. Traverse, MDPrincipal Investigator, TIME Study
Minneapolis Heart Institute at Abbott Northwestern HospitalUniversity of Minnesota Medical School
Cardiovascular Cell Therapy Research Network (CCTRN)
2012 Scientific Sessions of the AHA
The TIME Randomized TrialThe TIME Randomized Trial: : Effect of Intracoronary DeliveryEffect of Intracoronary Delivery of of
Autologous Bone Marrow Mononuclear Autologous Bone Marrow Mononuclear on Timing of Delivery following AMI on on Timing of Delivery following AMI on
Left Ventricular FunctionLeft Ventricular Function
![Page 2: Jay H. Traverse, MD Principal Investigator, TIME Study Minneapolis Heart Institute at Abbott Northwestern Hospital University of Minnesota Medical School](https://reader030.vdocuments.us/reader030/viewer/2022032722/56649ced5503460f949ba726/html5/thumbnails/2.jpg)
Organizational Structure: NHLBI Cardiovascular Cell Therapy Research Network (CCTRN)
Data Coordinating CenterData Coordinating CenterUTSPHUTSPHMoyéMoyé
NHLBINHLBISkarlatosSkarlatos
Texas Heart Texas Heart InstituteInstitute
WillersonWillerson
Texas Heart Texas Heart InstituteInstitute
WillersonWillerson
U FLU FLPepinePepineU FLU FL
PepinePepine
Cleveland Cleveland ClinicClinicEllisEllis
Cleveland Cleveland ClinicClinicEllisEllis
Minneapolis Minneapolis Heart InstituteHeart Institute
HenryHenry
Minneapolis Minneapolis Heart InstituteHeart Institute
HenryHenry
VanderbiltVanderbiltUniversityUniversity
ZhaoZhao
VanderbiltVanderbiltUniversityUniversity
ZhaoZhao
Cell ProcessingCell Processing Cell ProcessingCell Processing Cell ProcessingCell Processing Cell ProcessingCell Processing Cell ProcessingCell Processing
Steering CommitteeSteering CommitteeSteering CommitteeSteering Committee
ChairChairSimariSimari
Skills Development
Core
Skills Development
Core
Skills Development
Core
Skills Development
Core
CellProcessing
QC LabQC Lab
Biorepository, cMRI, Echo, MVO2, SPECT Core LabsCore Labs
DSMBDSMBDSMBDSMBPRCPRCPRCPRC
2
PDCPDC P & PP & P
Satellites:United Heart & Vascular ClinicMetro Cardiology Consultants
UMNMayo Clinic
Satellites:United Heart & Vascular ClinicMetro Cardiology Consultants
UMNMayo Clinic
Satellites:Pepin Heart Institute
Satellites:Pepin Heart Institute
Satellites:University Hospitals
Satellites:University Hospitals
![Page 3: Jay H. Traverse, MD Principal Investigator, TIME Study Minneapolis Heart Institute at Abbott Northwestern Hospital University of Minnesota Medical School](https://reader030.vdocuments.us/reader030/viewer/2022032722/56649ced5503460f949ba726/html5/thumbnails/3.jpg)
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.
33
![Page 4: Jay H. Traverse, MD Principal Investigator, TIME Study Minneapolis Heart Institute at Abbott Northwestern Hospital University of Minnesota Medical School](https://reader030.vdocuments.us/reader030/viewer/2022032722/56649ced5503460f949ba726/html5/thumbnails/4.jpg)
• 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
TIME Study Design
![Page 5: Jay H. Traverse, MD Principal Investigator, TIME Study Minneapolis Heart Institute at Abbott Northwestern Hospital University of Minnesota Medical School](https://reader030.vdocuments.us/reader030/viewer/2022032722/56649ced5503460f949ba726/html5/thumbnails/5.jpg)
Echo EF≤45%
TIME Study Flow
Informed Consent
Baseline cMRI
6-mos Primary
Measures cMRI
Primary Measures
cMRI
6-mos
Bone Marrow
Aspiration/Cell Processing
PCI + Stent
Meets Inclusion/ Exclusion
Criteria Index AMI
Cell Product 150x10Cell Product 150x1066 TNCs (n=43, D3; n=36, D7) TNCs (n=43, D3; n=36, D7)
Cell Free Placebo (n=24, D3; n=17, D7)Cell Free Placebo (n=24, D3; n=17, D7)
IC Treatment
IC Treatment
R= Randomization (2 BMC:1 Cell-Free)
CP-Quality Control
Biorepository Cell Function
Core5
![Page 6: Jay H. Traverse, MD Principal Investigator, TIME Study Minneapolis Heart Institute at Abbott Northwestern Hospital University of Minnesota Medical School](https://reader030.vdocuments.us/reader030/viewer/2022032722/56649ced5503460f949ba726/html5/thumbnails/6.jpg)
Cell Processing• Utilized local, automated cell processing• Sepax System– Automated processing– Includes cell washing– Closed system– Sterile disposable set
• Validated by extensive pre-clinical testing
Sepax vs. Manual Ficoll• No difference in cell recovery, migration or CFU
ability• Equivalent perfusion in hindlimb ischemia model
BMCFicoll
Manual Sepax6
![Page 7: Jay H. Traverse, MD Principal Investigator, TIME Study Minneapolis Heart Institute at Abbott Northwestern Hospital University of Minnesota Medical School](https://reader030.vdocuments.us/reader030/viewer/2022032722/56649ced5503460f949ba726/html5/thumbnails/7.jpg)
Baseline Characteristics
7
![Page 8: Jay H. Traverse, MD Principal Investigator, TIME Study Minneapolis Heart Institute at Abbott Northwestern Hospital University of Minnesota Medical School](https://reader030.vdocuments.us/reader030/viewer/2022032722/56649ced5503460f949ba726/html5/thumbnails/8.jpg)
Treatment Times (Median)
8
BMC (N=24)
Placebo (N=17)
BMC (N=43)
Placebo (N=24)
3 Days
7 Days
![Page 9: Jay H. Traverse, MD Principal Investigator, TIME Study Minneapolis Heart Institute at Abbott Northwestern Hospital University of Minnesota Medical School](https://reader030.vdocuments.us/reader030/viewer/2022032722/56649ced5503460f949ba726/html5/thumbnails/9.jpg)
9
Cell Characteristics
![Page 10: Jay H. Traverse, MD Principal Investigator, TIME Study Minneapolis Heart Institute at Abbott Northwestern Hospital University of Minnesota Medical School](https://reader030.vdocuments.us/reader030/viewer/2022032722/56649ced5503460f949ba726/html5/thumbnails/10.jpg)
Primary Endpoint: Global
10
No difference in the change in LVEF between BMC (n=75) and Placebo (n=37) groups from baseline to 6 months
![Page 11: Jay H. Traverse, MD Principal Investigator, TIME Study Minneapolis Heart Institute at Abbott Northwestern Hospital University of Minnesota Medical School](https://reader030.vdocuments.us/reader030/viewer/2022032722/56649ced5503460f949ba726/html5/thumbnails/11.jpg)
11
Results for both infarct zone and border zone wall motion were also not significant by therapy group for 3 days, 7 days, or overall.
Effect of Delivery Timing on the Change from Baseline to Six Months for LVEF
![Page 12: Jay H. Traverse, MD Principal Investigator, TIME Study Minneapolis Heart Institute at Abbott Northwestern Hospital University of Minnesota Medical School](https://reader030.vdocuments.us/reader030/viewer/2022032722/56649ced5503460f949ba726/html5/thumbnails/12.jpg)
Primary Endpoint: Regional
12
No difference in the change of regional wall motion in the infarct and border zone between baseline and 6 months
![Page 13: Jay H. Traverse, MD Principal Investigator, TIME Study Minneapolis Heart Institute at Abbott Northwestern Hospital University of Minnesota Medical School](https://reader030.vdocuments.us/reader030/viewer/2022032722/56649ced5503460f949ba726/html5/thumbnails/13.jpg)
Secondary Endpoints:Infarct Size and LV Volumes
13
![Page 14: Jay H. Traverse, MD Principal Investigator, TIME Study Minneapolis Heart Institute at Abbott Northwestern Hospital University of Minnesota Medical School](https://reader030.vdocuments.us/reader030/viewer/2022032722/56649ced5503460f949ba726/html5/thumbnails/14.jpg)
14
Clinical/Safety Outcomes at 6-month Endpoint Window
![Page 15: Jay H. Traverse, MD Principal Investigator, TIME Study Minneapolis Heart Institute at Abbott Northwestern Hospital University of Minnesota Medical School](https://reader030.vdocuments.us/reader030/viewer/2022032722/56649ced5503460f949ba726/html5/thumbnails/15.jpg)
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.
15
![Page 16: Jay H. Traverse, MD Principal Investigator, TIME Study Minneapolis Heart Institute at Abbott Northwestern Hospital University of Minnesota Medical School](https://reader030.vdocuments.us/reader030/viewer/2022032722/56649ced5503460f949ba726/html5/thumbnails/16.jpg)
Acknowledgements
16
• 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