PRET. Patients Prone to Recurrence after Endovascular Treatment XIX SYMPOSIUM NEURORADIOLOGICUM

Transcription

1 PRET Patients Prone to Recurrence after Endovascular Treatment XIX SYMPOSIUM NEURORADIOLOGICUM

2 Background and purpose Angiographic recurrences risk factors Size 10mm Recurrent aneurysm 50% of recurrence

3 Background and purpose These aneurysms are poorly represented in clinical trials HELPS study included some large aneurysms (~25%) and no recurrent aneurysms

4 Background and purpose New coils have been designed to preserve the safety while improving on long-term efficacy No scientific evidence Some concerns have been raised about the safety of hydrocoils in large aneurysms

5 Primary hypothesis The use of hydrogel-coated coils in patients with large aneurysms or presenting major recurrences after a previous endovascular treatment decreases the recurrence rate from 50% to 32% at 18 months as compared to bare platinum coils

6 Secondary hypothesis The number of adverse events is similar in both groups. Morbidity and mortality related to treatment remains unchanged

7 Design Multicentre, randomized, controlled trial with concealed allocation Two cohorts, 250 subjects each, independently randomized PRET 1 : One ruptured or unruptured aneurysm, never treated, 10 mm or larger PRET 2 : A major (i.e. requiring retreatment) recurrence after previous coiling It is possible for a site to recruit selectively in either cohort, depending on site participation in other competing trials

8 Inclusion Criteria PRET-1 or PRET-2 lesion Anatomy of lesion is such that treatment is possible with either type of coil Endovascular physician is indifferent to the use of either type of coil Patient is 18 or older Life expectancy is more than 2 years Exclusion criteria Design Other aneurysms requiring treatment during the same session Associated cerebral AVMs Parent vessel occlusion without simultaneous endosaccular coiling of the aneurysm is the primary intent of the procedure Contraindication to endovascular treatment, angiography or anesthesia

9 Design Schedule of evaluation following endovascular intervention Dm1 1 month FU Dm6 6 (4-8) months FU Dm12 12 (10-14) months FU Dm18 18 (16-22) months FU Clinical X X X X Angiographic X X

10 Outcomes Primary end point (recurrence rate) Angiographic recurrence (6 months or 18 months), with or without retreatment (independent core lab) SAH or mass effect Secondary end point (safety) Procedural safety Mortality rate Morbidity rate, possibly or probably related to aneurysm or its treatment (Adjudication Committee)

11 Randomization - Recruitment Stats Site and Subject Accrual Mar 07 Subjects Sites Jun 07 Sep 07 Dec 07 Mar 08 Jun 08 TOTAL Subjects : 178; TOTAL Sites : 26 Semptember Sep 08 Dec 08 Mar 09 Jun 09 Sep 09 Dec 09 Mar 10 Jun 10 Sep

12 Randomization - Recruitment Stats List of Sites Active Sites United States The Methodist Hospital Medical University of South Carolina (SUNY) Stony Brook University Medical Center Oregon Health & Science University Mayo Clinic Rochester Cleveland Clinic Columbia University Medical Center (SUNY) University of Buffalo - Kaleida Health Shands - University of Florida Hospital University of Virginia Health Borgess Medical Center Drs Klucznick & Diaz, Marilyn Bautista Dr Turk, Adrian Parker Dr Woo, Susan Fiore & Marlene Baumeister & Dawn Madigan Dr Barnwell, Sarah Ross Dr Kallmes, Leigh Gray Dr Masaryk, Doreen Andrew-Hinders & Therese Wheeler Dr Lavine, Virginia Cox & Dave Ryan Dr Levy, Anne-Marie Crumlish & Maureen Donovan Dr Mocco, Adrienne Royster&Bree Burks Dr Evans, Claire McKinley & Parchayi Dalal Dr Al-Ali, Sarah Walker West Virginia University Hospital Drs Carpenter and Rai, Jennifer Domico SUNY Upstate Medical University Dr Deshaies, Susan Hemingway & Tina Craig University of Cincinnati Medical Center Dr Ringer, Carolyn Koenig & Rebecca Reinert Washington University in St Louis Dr Moran, Angela Campbell & Robin Haverman University of Wisconsin Hospital and Clinics Dr Aagaard Kienitz, Silvia Skripkauskas TOTAL United States : 16 Active Sites Canada CHUM- Notre Dame The Ottawa Hospital Japan Kobe City Medical Center General Hospital France CHU Nancy - Hôpital Central CHU Henri Mondor - Hôpital Henri Mondor CHU de Nantes - Hôpital Guillaume et René Laennec CHU de Montpellier - Hôpital Gui de Chauliac CHU Bordeaux - Hôpital Pellegrin United Kingdom Leeds General Infirmary Chile Instituto de Neurocirugia Dr Asenjo Drs Roy & Raymond, Assia Bellblidia Dr Santos, Betty Anne Schwarz Drs Sakai & Imamura Pr Bracard Dr Gallas Dr Desal Dr Bonafé Dr Barreau Dr Goddard Drs Bravo & Sordo TOTAL non-us : 10 The site in red has withdrawn its participation

13 Randomization - Recruitment Stats Performance of Sites per Country

14 Demographics PRET-1; N = 91 PRET-2; N = 87 N = 91 Age - yr Mean (SD) 61 (11) Range Gender - % Female 75 Male 25 Number of aneurysms identified at angiography - % N = 87 Age - yr Mean (SD) 57 (11) Range Gender - % Female 67 Male 33 Number of aneurysms identified at angiography - % SAH - % Yes 23 No 77 SAH - % Yes 5 No 95

15 Target Aneurysm Parameters PRET-1; N = 91 PRET-2; N = 87 N = 91 Target aneurysm size - mm Mean (SD) 15 (5) Range N = 87 arget aneurysm size - mm Mean (SD) 12 (7) Range 2-40 Target aneurysm location - % Anterior 57 Posterior 43 arget aneurysm location - % Anterior 60 Posterior 40

16 Adverse Events AE Committee review on June 4, 2010 (145 enrolled): 48 Validated AEs Severity Attribution Minor or Moderate Severe Validated AEs 29 19

17 Adverse Events AE distribution / Severity Group V Group D Minor or Moderate Severe 0

18 Adverse Events Causality Attribution RT-S RT-P RA U Validated AEs Categories: RT-S; strictly related to treatment: any M&M associated with a procedural event or complication. RT-P; possibly related to treatment: any M&M occuring within 30 days RA; related to aneurysm U; unrelated to the aneurysm or its treatment

19 Adverse Events Severity/Causality distribution Minor or Moderate Severe RT-S 16 7 RT-P 12 6 RA 0 3 U 1 3

20 Adverse Events Severe, Treatment related AEs 4 Group V Group D RT-Strictly RT-Possibly 0

21 Randomization Problems Problem preventing recruitment: Cost of Hydrocoil Problems slowing recruitment: Not every eligible patient is recruited Competition with other trials Competition with other devices *

22 Thank you