Trial and Cost Effectiveness Evaluation of Intra arterial Thrombectomy in Acute Ischemic Stroke

Transcription

1 Trial and Cost Effectiveness Evaluation of Intra arterial Thrombectomy in Acute Ischemic Stroke S. Bracard, F. Guillemin, X. Ducrocq for the THRACE investigators

2 Disclosure Personal: No disclosure Study funded by the French Ministry of Health (STIC 2009)

3 THRACE Randomized, multicentre, controlled trial Primary objective: to determine whether a combined IV/IAMT is superior to standard IV rt-pa alone in patients with moderate-to-severe strokes (NIHSS:10-25) due to large artery occlusion when IV tpa is initiated within 4h of acute ischemic stroke onset

4 THRACE secondary objective: to determine the cost effectiveness of combined IV/IAMT compared with IV rt-pa alone as measured by differences in utilization of resources and quality of life over 12 months after the stroke between the two treatments arms Economic hypothesis: IV/IA therapy is cost-effective at 3 months compared with IV rt-pa alone and provides cost-savings or is cost neutral at 12 months

5 THRACE All the patients received standard-dose (0.9 mg/kg) IV rtpa. Perfusion-time allowed to complete the determination of trial eligibility, obtain consent/ authorization from the patient or legal representative and to randomize (1:1) IV alone vs IV+IAMT IAMT arm: if there was no or a minor neurological improvement (<5 points NIHSS) immediate angiography. If an appropriate thrombus was identified, the neurointerventionalist could select the device in a regularly updated list: Merci, Catch, Solitaire, Revive, Trevo, Penumbra 3d Separator and ACE, Mindframe Capture and Flow, preset (Phenox), ERIC IAM treatment should have begun within 5 hours and must be completed within 6 hours of stroke onset.

6 arrival Inclusion criteria IV THROMBOLYSIS Inform et consent Inclusion Randomization IVT arm IVT + MT arm NIHSS Improvement 4 No improvement Angiography TICI 2 TICI < 2 stop THROMBECTOMY Same medical treatments and follow up

7 follow-up 24h Day 7 or discharge 3 Month 12 month clinical evaluation NIHSS Barthel mrs Quality of life evaluation CT/MRI

8 Inclusion - exclusion criteria Main inclusion criteria: age years; baseline NIHSS score: 10 to 25 Intracranial ICA occlusion, M1 and upper part of the BA initiation of IV rtpa within 4h from stroke onset. Exclusion criteria: those of the routine use of IV rtpa in France CT exclusion criteria include hemorrhage of any degree and evidence of intraparenchymal tumor,. NIHSS > 25 Time to treatment > 4h Ipsilateral cervical ICA occlusion or sub occlusive stenosis Life expectancy < 3 months any imaging based exclusion criteria either ASPECT score nor perfusion parameters

9 planned sample size was 480 patients Inclusions 12,9% 26 active centers in France 414 patients randomized.

10 Inclusions 414 patients 2 consent withdrawal 412 patients 10 with incomplete data 402 patients with monitored and validated complete data 4 lost in follow up 6 patients alive with unknown mrs at 3 month 51 deaths before 3 months 351 with 3 month clinical FU 10

11 clinical data total n=412 IVT n=208 IVT+MT n=204 Age 62.8 (13.7) 62.9 (14.5) 62.6 (13.3) Male sex 53,4 % 104 (50.0%) 116 (56.9%) NIHSS mean (std) 17.4 (4.2) 17.1 (4.3) 17.6 (4.0) median (IQR) 18 (14-21) 17 (13-20) 18 (15-21)

12 clinical data Comorbidities and risk factors total n=412 IV n=208 IVT+MT n=204 Chi-2 p= Hypertension 52.8% 57.3% 48.0% : 0.06* Hypercholesterolemia 51.4% 57.7% 44.7% : 0.01* Current smoker 26.5% 23.5% 30.9% : 0.11 Former smoker 18.5% 19.3% 18.1% : 0.77 Coronary disease 15.8% 15.2% 16.4% : 0.73 Diabete 12.8% 17.1% 8.5% : 0.01* previous stroke 6.2% 6.8% 7.2% : 0.89 * No statistically significant interactions were observed in the treatment group for these risk factors

13 localisations total n=409 IVT n=208 IVT+MT n=204 C1 63 (15,4%) 39 (18.8%) 24 (11.9%) M1 340 (83.1%) 164 (79.2%) 176 (87.1%) M2* 2 (0.5%) 2 (0.5%) (0.0%) BA 4 (1%) 2 (1.0%) 2 (1.0%) Cervical ICA 0 * M1-M2 junction, core lab attribution

14 imaging ASPECT total IVT IVT+MT score (398) (N=202) (N=196) (14 3%) 35 (17 3%) 22 (11 2%) (33 1%) 52 (25 7%) 80 (40 8%) (52 5%) 115 (56 9%) 94 (48 0%)

15 Workflow times Workflow times- min IVT (N=208) IVT+MT (N=204) From onset to IV thrombolysis Median (IQR) 153 ( ) 150 ( ) From onset to randomization Median (IQR) 170 ( ) 168 ( ) From onset to thrombectomy Median (IQR) 250 ( ) From onset to the end of thrombectomy. Median (IQR) 303 ( )

16 Clinical evolution at 3 months total n=402 IVT n=202 IVT+MT n=200 P value OR (95% CI) Rankin (47,5%) Rankin (52,5%)

17 Clinical evolution at 3 months total n=402 IVT n=202 IVT+MT n=200 P value OR (95% CI) Rankin (47,5%) 85 (42,1%) Rankin (52,5%) 117 (57,9%)

18 Clinical evolution at 3 months total n=402 IVT n=202 IVT+MT n=200 P value OR (95% CI) Rankin (47,5%) 85 (42,1%) 106 (53%) Z proportion test: ( ) Rankin (52,5%) 117 (57,9%) 94 (47%)

19 ordinal logistic regression: OR, 1 39; 95% CI, ; p=0 05

20 Clinical evolution Deaths and adverse events before 3 month evaluation total n=412 IVT n=208 IV-IAMT n=204 P value OR (95% CI) deaths 52 (12.7%) 27 (13.1%) 24 (11.9%) ( ) adverse events 111 (28,8%) 65 (31.6%) 55 (27.2%) ( )

21 Primary and secondary outcomes. Treatment effects Secondary outcomes IVT (N=202) IVTMT (N=200) P value NIHSS score at 7 days. Mean (SD) Median (IQR) 9 4 (7 7) 8 (2-16) 7 7 (8 7) 4 (1-14) NIHSS score at 3 months. Mean (SD) Median (IQR) 5 9 (6 0) 4 (0-10) 4 7 (6 0) 2 (0-8) 0 01 Barthel index at 3 months: no (%) 79 (49 1%) 92 (60 5%) 0 04 EQ-5D at 3 months Mean (SD) Median (IQR) (0 39) ( ) (0 40) ( ) 0 38 Symptomatic haemorrhages at 24 hours no (%) 3 (1 6%) 4 (2 2%) 0 71 Asymptomatic haemorrhages at 24 hours no (%) 8 (4,4%) 3 (1.7%) 0.14

22 Revascularization mtici 2b-3 no/total (%) 95/138 (68 8%) Initial mtici 0 mtici 1 mtici 2A mtici 2B N=123 N=9 N=1 N=2 Final mtici 0 19 (15.6%) 0 (0.0%) 0 (0.0%) 0 (0.0%) mtici 1 5 (4.1%) 1 (11.1%) 0 (0.0%) 0 (0.0%) mtici 2A 15 (12.3%) 1 (11.1%) 0 (0.0%) 0 (0.0%) mtici 2B 57 (46.7%) 4 (44.4%) 1 (100.0%) 2 (100.0%) mtici 3 26 (21.3%) 3 (33.3%) 0 (0.0%) 0 (0.0%) from 53% in 2011 to 80% in 2014!

23 Effect modification according to patients characteristics Odds Ratio estimates from logistic regression

24 Conclusions Bridging therapy combining IV rtpa +mechanical thrombectomy is superior to IV rtpa alone in patients with a moderate to severe stroke (NIHSS 10-25) due to an occlusion of a large artery of the anterior circulation within 6 hours after stroke onset

25 Thanks to the patients and the investigators from: Nancy, Paris- Pitié Salpétrière, Reims, Nantes, Rennes, Paris-Ste Anne, Bordeaux, Dijon, Angers, Nice, Lyon, Paris-Lariboisière, Fondation Rothschild, Poitiers, Clermont-Ferrand, Grenoble, Foch Suresnes, Colmar, Paris- Bicêtre, Limoges, Besançon, Toulon, Montpellier, Lille, Caen, Réunion and to the Clinical Research teams

26 S. Bracard, F. Guillemin, X. Ducrocq for the THRACE investigators