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Douglas W. Losordo, M.D. on behalf of ACT34-CMI Investigators

Randomized, Double-Blind, Placebo-Controlled Study of Intramyocardial CD34+ Cell Therapy for Refractory Angina. Douglas W. Losordo, M.D. on behalf of ACT34-CMI Investigators Northwestern University, Chicago, USA. Presenter Disclosure Information. Douglas Losordo, M.D.

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Douglas W. Losordo, M.D. on behalf of ACT34-CMI Investigators

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  1. Randomized, Double-Blind, Placebo-Controlled Study of Intramyocardial CD34+ Cell Therapy for Refractory Angina Douglas W. Losordo, M.D. on behalf of ACT34-CMI Investigators Northwestern University, Chicago, USA

  2. Presenter Disclosure Information Douglas Losordo, M.D. The following relationships exist related to this presentation: • Study Sponsored by Baxter Healthcare • Dr. Losordo was previously a paid consultant for Baxter Healthcare, receiving “modest” consulting fees by ACC definition.

  3. ACT34-CMI Core Labs • Exercise Treadmill Time (ETT) Core Lab • Dr. Ernest Gervino • Cardiovascular Core Laboratories – SPECT • James Udelson, MD

  4. ACT34-CMI Core Labs • Magnetic Resonance Imaging / PERFUSE • Dr. Evan Appelbaum • Quality of Life • Dr. David Cohen

  5. Study Logistics • Data Safety Monitoring Board • Dr. Jeffrey Brinker, Chair • Dr. Kenneth Ellenbogen • Dr. Armand Keating • Dr. George Vetrovec • Dr. James Dziura • Brigham and Women’s Hospital, Clinical Endpoint Committee • Dr. Marc Pfeffer • Dr. Akshay Desai • Dr. Peter Finn

  6. Study Logistics • Duke Clinical Research Institute (statistical analysis) • Robert Harrington, MD • Karen Pieper, M.S. • Robert Clare, M.S. • Biologics Delivery Systems: NOGA Mapping Support

  7. Phase II ACT34–CMI Study Design Screening and Baseline Visits • Subject population (n=167) • 21-80 yrs • CCS class III or IV Angina • Attempted “best” medical therapy • Non-candidate for Surgical/Perc. revasc. • Ischemia on SPECT • 3-10 min. mod. Bruce protocol with angina or anginal equivalent at baseline Cell Mobilization (GCSF 5mcg/kg/d x 5d) Apheresis on Day 5 Randomization 1 x 10^5 CD34+ cells/kg (n = 55) Placebo (n = 56) 5 x 10^5 CD34+ cells/kg (n = 56) Endomyocardial Mapping and Injection with NOGA Isolex selected CD34+ cells / Placebo Rx Follow-up Safety and Efficacy Assessments: 1 - 7 days, and 1, 3, 6, and 12 months; ETT at 3, 6, 12 months MRI at 6 months, SPECT at 6 & 12 months

  8. Enrollment/Demographics • Enrollment • First subject enrolled (screened): 04 April 2006 • First subject treated: 18 May 2006 • Last subject screened: 15 Jan 2008 • Last subject treated: 13 March 2008 • Last subject 6 Mo follow up: 01 Oct 2008 • Last subject 12 Mo follow up: 05 Mar 2009 • 321 subjects signed informed consent • 167 subjects underwent injection procedure • 162 subjects completed 6 mo follow up

  9. Enrollment/Demographics

  10. Safety • Procedural Events • 2 Perforations (1.2%) • 1 Death (0.6%)

  11. Major Adverse Cardiac Events (12 Months)

  12. ACT-34 CMI: Reduction in Angina Anginal Episodes per Week Change from baseline at 6 months P=0.14 Poisson Regression with Extra Variability

  13. ACT-34 CMI: Reduction in Angina Anginal Episodes per Week Change from baseline at 6 months P=0.04 Analysis of Variance (ANOVA)

  14. ACT-34 CMI: Increase in Exercise Time Total ETT Time Change from baseline at 6 months p=0.013 Seconds

  15. ACT-34 CMI: Reduction in Time to Resolution of Angina Time to Resolution of Angina

  16. ACT-34 CMI: More Rapid Resolution of Angina Change in Time to Resolution of Angina p=0.048

  17. ACT-34 CMI: Increased RPP at Resolution of Angina Rate-Pressure Product at Resolution of Angina

  18. ACT-34 CMI: Increase in Time to Angina Time to Angina Change from baseline at 6 months p=0.247

  19. ACT-34 CMI: Angina Stability Score Change from Baseline - 6 Months p=0.042

  20. ACT-34 CMI: SPECT Total Severity Score - Stress Change from baseline at 6 months p=0.002

  21. Summary • Feasibility • Phase 2 study successfully enrolled 167 pts at 26 centers across US • Safety • No evidence of harm by injection of autologous CD34+ cells; Net trends toward decreased MACE

  22. Summary (2) • Bioactivity • Angina frequency • ETT • Total Time increased • Time to Resolution of Angina • Time to Angina • Change in RPP at resolution of Angina

  23. Conclusions • 167 “no-option” refractory angina pts enrolled in RCT of intramyocardial autologous CD34+ stem cell therapy • Safety profile appears acceptable • Significant improvement in ETT - first in this population • Reduced angina; trend vs. significant

  24. Ongoing • Awaiting 12 month data • 2nd year follow up study

  25. Limitations • Phase 2 study - not conclusive • 12 mo data pending

  26. Questions • Effects of GCSF • Non-linear dose response

  27. Thank you for your attention

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