Best medical therapy (includes iv t-pa in eligible patients)

Transcription

1 UDATE ON REVASCAT: (Randomized Trial Of Revascularization With Solitaire FR Device Versus Best Medical Therapy In The Treatment Of Acute Stroke Due To Anterior Circulation Large Vessel Occlusion Presenting Within 8 Hours Of Symptom Onset) Tudor G. Jovin, M.D. Associate Professor of Neurology and Neurosurgery Director, UPMC Stroke Institute Director, UPMC Center for Neuroendovascular Therapy University of Pittsburgh Medical Center

2 DISCLOSURES Consultant/Advisory Board: Ownership Interest: Silk Road Medical modest Consultant (DSMB): Johnson& Johnson, modest Consultant (Steering Committee): Neuravi, modest Consultant/Advisory Board: Covidien/Medtronic, unpaid Consultant: Stryker Neurovascular, unpaid PI: REVASCAT (Fundacio Ictus Malaltia Vascular), unpaid PI: DAWN (Stryker Neurovascular), unpaid

3 Title Sponsor Funding Study device Control intervention (IV-tPA yes/no?) Study population Objective Design Sample size Randomized Trial Of Revascularization With Solitaire FR Device Versus Best Medical Therapy In The Treatment Of Acute Stroke Due To Anterior Circulation Large Vessel Occlusion Presenting Within 8 Hours Of Symptom Onset Fundacio Ictus Malaltia Vascular, Barcelona, Spain Fundacia Ictus Malaltia Vascular ( by means of unrestricted grant from Covidien) Solitaire FR device Best medical therapy (includes iv t-pa in eligible patients) Subjects presenting with acute ischemic stroke within 8 hours from symptom onset with absence of large core (ASPECTS based), NIHSS >5 and whose strokes are attributable to an occlusion of the internal carotid or proximal MCA (M1) arteries. Subjects age 18-80* are either ineligible for IV alteplase or have received IV alteplase therapy without recanalization. To evaluate the hypothesis that mechanical embolectomy with the Solitaire FR device is superior to medical management alone in achieving favourable outcome in the distribution of the modified Rankin Scale scores at 90 days in subjects presenting with acute large vessel ischemic stroke < 8 hours from symptom onset. Multicenter, prospective, randomized 1:1, open-label study with blinded evaluation. Sequential design with three pre- planned interim analyses. Sample size was projected to be a maximum of 690 patients for a difference in treatment effect of 10%. Study terminated after first interim analysis (n=174) due to loss of equipoise. * After 160 pts amendment to include age with ASPECTS > 8

4 Primary efficacy endpoint Distribution of the modified Rankin Scale scores at 90 days as evaluated by two separate certified assessors masked to treatment: STAIR, 2015 Washington, DC Molina C et al. Int J Stroke 2014

5 METHODS Evaluation of mrs scores at 90 days Local evaluation Central blinded evaluation - Face-to-face interview - Certified local neurologist - Blinded to treatment assignment - Structured interview First trial half: one certified nurse by structured phone interview to the patient/relative. Second trial half (after protocol amendment): one expert neurologist looking at video recording of the local face-to-face interview Video recordings were transferred via FTP to the external assessor in a blinded fashion STAIR, 2015 Washington, DC 7

6 Consort flow diagram Randomized (n=207) Removed due to withdraw informed consent (n=1) Intervention Control Received tpa (n=70) Did not receive tpa (n=33) Received tpa (n=80) Did not receive tpa (n=23) Allocated to intervention arm (n=103) -Did not undergo thrombectomy (n=5)* Allocated to control arm (n=103) Cross over from control to endovascular (n=0) Received endovascular treatment (n=98)* Lost to follow-up (n=0) Lost to follow-up (n=0) 103 Evaluable subjects 103 Evaluable subjects * TICI 3 or TICI 2b on conventional angiography; 1 an 4 patients evaluated by phone interview due to poor conditions (Rankin 4 or 5) Jovin TG et al. NEJM 2015 STAIR, 2015 Washington, DC

7 Variable Thrombectomy (n=103) Control (n=103) Difference (95%CI) Ratio (95%CI) Adjusted Ratio (95%CI) Safety variables Death at 90 days no.(%) 19 (18.4%) 16 (15.5%) -2.9 (-13.2, 7.3) 1.2 (0.6, 2.2) 1.1 (0.8, 1.4) Symptomatic intracranial hemorrhage (SITS-MOST) no. (%)* Symptomatic intracranial hemorrhage (ECASS II) no. (%) 2 (1.9%) 2 (1.9%) 0.0 (-3.8, 3.8) 1.0 (0.1, 7.0) 5 (4.9%) 2 (1.9%) -2.9 (-7.8, 2.0) 2.5 ( ) * Symptomatic (neurologic worsening 4 point in the National Institutes of Health Stroke Scale) ICH adjudicated by the Critical Events Committee plus PH2 or rph2 classified according to the neuroimaging Corelab STAIR, 2015 Washington, DC Jovin TG et al., NEJM 2015

8 Primary Outcome variable: modified Rankin Scale Common Odds Ratio, 1.71; 95%CI, * (N=103) (N=103) Patients (%) * Adjusted for minimization factors and IV tpa therapy Jovin TG et al., NEJM 2015 STAIR, 2015 Washington DC

9 Outcome Modified Rankin scale score 0-2 at 90 days - no (%) Dramatic neurologic improvement at 24h Thrombectomy (n=103) Secondary outcomes Control (n=103) Effect variable 45 (43.7) 29 (28.2) Odds ratio 59 (57.8) 20 (20.0) Odds ratio Unadjusted Value (95% CI) Adjusted value (95% CI) 2.0 (1.1, 3.5) 2.12 (1.1, 4.0) 5.5 (2.9, 10.3) 5.8 (3.0, 11.1) no. (%)* NIHSS score at 90 days Median [IQR] 2.0 (0.0, 8.0) 6.0 (2.0, 11.0) Beta -2.7 (-4.4,-0.9) -2.4 (-4.1,-0.8) Barthel index of at 90 days no. (%) 47 (57.3) 23 (26.4) Odds ratio 3.7 (2.0, 7.1) 4.2 (2.1, 8.4) EQ-5D score at 90 days Median [IQR] 0.65 [0.21, 0.79] 0.32 [0.13, 0.70] Beta 0.13 (0.03, 0.23) 0.11 (0.02, 0.21) Modified TICI no. (%) 2b-3 Pre 3 (3.0) Post 67 (65.7) * Dramatic neurological improvement as determined by a NIHSS drop of 8 or NIHSS 0-2 at 24 hours Adjudicated by the independent agio Corelab Jovin TG et al., NEJM 2015 STAIR, 2015 Washington, DC

10 SENSITIVITY ANALYSES OR (95%CI) Final analysis (video/local) 1.71 (95%CI, ) Sensitivity analysis I (central: phone/video) 1.83 (95%CI, ) Sensitivity analysis II (local investigators) 1.93 (95%CI, ) Favors endovascular treatment STAIR, 2015 Washington, DC Lopez Cancio E et al., ESOC 2015

11 AGREEMENT OF DIFFERENT EVALUATIONS LOCAL-EXTERNAL % OF TOTAL AGREEMENTS WEIGHTED KAPPA n/n % CI 95% wk CI 95% Phone-based 75/ % % Central lower in 22.5% and higher in 15% Video-based 92/ % % Central lower in 6.6% and higher in 6.6% Lopez Cancio et al., ESOC 2015

12 REVASCAT A clinical trial embeded within, SONIIA a population based reperfusion registry ESOC 2015 Glasgow Abilleira S. et al., Stroke /12

13 STAIR, 2015 Washington, DC Urra X et al,stroke 2015, in press 5/12 Near-consecutive enrolment 88%

14 ESOC STAIR, Washington, Glasgow DC Urra X et al,stroke 2015, in press 10/12 SONIIA REGISTRY DURING REVASCAT Functional outcomes

15 STAIR, 2015 Washington, DC LIKELIHOOD OF GOOD OUTCOME ACCORDING TO TIME INTERVALS FROM SX S ONSET TO REPERFUSION AND ASPECTS Ribo et. al., ESOC % for each 30-28% for each 30-44% for each 30-50% for each 30 Only OR values with 95% CI < 1 are shown

16 Investigators STAIR, 2015 Washington DC SONIIA Registry Miquel Gallofré Sonia Abilleira Other Comprehensive Stroke Center Hospital del Mar Hospital Parc Taulí 24 12/12