1. Click to edit Footer title style Randomized Trial of Bead Block TM vs Embosphere TM for UAE for Fibroids Robert L Worthington-Kirsch, MD, FSIR, FCIRSE, RVT, RPVI

2. Click to edit Footer title style Disclosures This study is supported by an unrestricted grant from Biocompatibles and Terumo Dr Worthington-Kirsch is an active consultant to Biocompatibles, Terumo, Biosphere Medical, and Vascular Solutions

3. Click to edit Footer title style Background UAE has been established as mainstream therapy for fibroid disease Embolic choice evolving Calibrated hydrogel spheres preferred Tris-acryl/gelatin most commonly used PVA hydrogel is an emerging alternative

4. Click to edit Footer title style PVA Hydrogel Spheres Very similar to soft contact lenses PVA has been used as implanted biomaterial since the 1940s Very different properties than non-hydrogel PVA preparations

5. Click to edit Footer title style Study Rationale Clinical experience suggests that BB as effective as ES for UAE Requires proper technique Randomized trial needed to confirm or disprove anecdotal experience

6. Click to edit Footer title style Study Design Non-inferiority 22 patients per arm gives desired power PRCT (Level I data) Patients not informed about embolic used MRI grader blinded for embolic used Reviewed/approved by FDA

7. Click to edit Footer title style Admission Criteria Similar to other UAE studies Women ages 30-50 Symptomatic fibroids without other uterine disease Uterus >250cc, <24 weeks

8. Click to edit Footer title style Study Design MRIs on designated magnet Pre-UAE, 3-7 days post-UAE, 3 months, 6 months Best protocol for each embolic BB – start with 700-900 ES – start with 500-700, unless Ovarian A seen Terumo Progreat microcatheter Consistent defined embolization endpoints

9. Click to edit Footer title style Embolization Endpoints New filling of Ovarian A or cross-uterine collaterals Retrograde flow around catheter tip “Plumping” of artery with injection No further filling of ascending branch

10. Click to edit Footer title style Outcome Measures MRI fibroid perfusion “immediate”, 3 months, 6 months Uterine/dominant fibroid size UFS-QOL 3 months, 6 months, 1 year

11. Click to edit Footer title style Study to Date 2 cohorts Site 1 – 22 patients Complete follow-up data set 1 technical failure (anatomic basis) Site 2 – 22 + 2 patients 1 withdrawal from initial 22 Follow-up complete except for 12 month QOLs 22 analyzable patients in each arm

12. Click to edit Footer title style Study to Date No serious complications All UAEs clinically successful per patients Including technical failure 3 “failures” to discuss in more detail

13. Click to edit Footer title style Study to Date – Follow Up 1 Week post-UAE (MRI only) – 43/44 (97%, 1 ES) 3 Mo post-UAE MRI – 36/44 (82%, 5 ES, 3 BB) QOL – 39/44 (88%, 3 ES, 2 BB) 6 Mo post-UAE MRI – 37/44 (84%, 4 ES, 3 BB) QOL – 43/44 (97%, 1 BB) 12 Mo post UAE (QOL only) – 21/21

14. Click to edit Footer title style MRI Grading Pre-UAE perfusion scored at 10 Global fibroid burden, not just dominant fibroid Follow-up perfusion scored 1-10 1 – Complete infarction all visible fibroids 1-2 - “Success” (10% or less residual perfusion) 3-4 – “Partial Success” (11-30% residual perfusion) 5 or higher - “Failure” (>30% residual perfusion)

15. Click to edit Footer title style Fibroid Perfusion

16. Click to edit Footer title style Volume

17. Click to edit Footer title style UFS-QOL Grading Symptom Score, QOL Score. QOL Subscales Change of 10 points or greater significant

18. Click to edit Footer title style UFS-QOL

19. Click to edit Footer title style UFS-QOL

20. Click to edit Footer title style QOL Subscales Bead Block Embosphere

21. Click to edit Footer title style QOL Subscales

22. Click to edit Footer title style QOL Subscales

23. Click to edit Footer title style QOL Subscales

24. Click to edit Footer title style QOL Subscales

25. Click to edit Footer title style Treatment Failures? Patient # 2-003 Embosphere Complete infarction at 1 week and 3 months Significant reperfusion (4) at 6 months SS94>44>0 QOL 86>89>96 Will symptoms recur?

26. Click to edit Footer title style Treatment Failures? Patient # 2-016 Bead Block Almost complete infarction (2) on all f/u MRIs SS41>69>66 (worsening) QOL 66>50>52 (borderline improvement)

27. Click to edit Footer title style Treatment Failures? Patient # 2-013 Embosphere Perfusion score 3 @ 1 week, then 2 SS47>25>31 QOL 53>56>51

28. Click to edit Footer title style Treatment Failures? General consensus in literature is that UAE failure rate is ~10%. 3 Failures out of 44 patients is not unexpected.

29. Click to edit Footer title style Data Supports Noninferiority UFS - QOL Symptom SeverityStudent TSig (  =95%) Baseline.3075Y 3 Month.2406Y 6 Month.1289Y Overall QOL Baseline to Baseline.8235Y 3 Mo BB vs ES.0005N 3 Mo change.1950Y 6 Mo BB vs ES.2002Y 6 Mo change37252Y

30. Click to edit Footer title style Data Supports Noninferiority Perfusion

31. Click to edit Footer title style Data Supports Noninferiority Volume Reduction

32. Click to edit Footer title style Spies – “How to Evaluate New Embolics” Well–defined inclusion/exclusion criteria Adequate sample size/power analysis Randomization by independent third party Double-blinding Identical care and follow-up

33. Click to edit Footer title style Spies – “How to Evaluate New Embolics” Well–defined inclusion/exclusion criteria Adequate sample size/power analysis Randomization by independent third party Double-blinding Identical care and follow-up

34. Click to edit Footer title style Spies – “How to Evaluate New Embolics” Well–defined inclusion/exclusion criteria Adequate sample size/power analysis Randomization by independent third party Double-blinding Identical care and follow-up

35. Click to edit Footer title style Spies – “How to Evaluate New Embolics” Well–defined inclusion/exclusion criteria Adequate sample size/power analysis Randomization by independent third party Double-blinding Identical care and follow-up

36. Click to edit Footer title style Spies – “How to Evaluate New Embolics” Well–defined inclusion/exclusion criteria Adequate sample size/power analysis Randomization by independent third party Double-blinding Identical care and follow-up

37. Click to edit Footer title style Spies – “How to Evaluate New Embolics” Well–defined inclusion/exclusion criteria Adequate sample size/power analysis Randomization by independent third party Double-blinding Identical care and follow-up

38. Click to edit Footer title style Spies – “How to Evaluate New Embolics” Intention to treat analysis Blinded imaging assessment Clear endpoint assessment UFS-QOL, Enhanced MRI Reporting

39. Click to edit Footer title style Spies – “How to Evaluate New Embolics” Intention to treat analysis Blinded imaging assessment Clear endpoint assessment UFS-QOL, Enhanced MRI Reporting

40. Click to edit Footer title style Spies – “How to Evaluate New Embolics” Intention to treat analysis Blinded imaging assessment Clear endpoint assessment UFS-QOL, Enhanced MRI Reporting

41. Click to edit Footer title style Spies – “How to Evaluate New Embolics” Intention to treat analysis Blinded imaging assessment Clear endpoint assessment UFS-QOL, Enhanced MRI Reporting

42. Click to edit Footer title style Spies – “How to Evaluate New Embolics” Intention to treat analysis Blinded imaging assessment Clear endpoint assessment UFS-QOL, Enhanced MRI Reporting

43. Click to edit Footer title style Spies – “How to Evaluate New Embolics” Intention to treat analysis Blinded imaging assessment Clear endpoint assessment UFS-QOL, Enhanced MRI Reporting

44. Click to edit Footer title style Questions?