Abstract 60: Outcomes Following Sonothrombolysis in Severe Acute Ischemic Stroke

Abstract

Background&Purpose: A recent meta-analysis showed that sonothrombolysis is safe and can double the rate of early recanalization in acute ischemic stroke (AIS). We sought to explore whether patients with severe strokes could clinically benefit from ultrasound amplification of tPA-induced recanalization. Subjects&Methods: We compared functional outcomes at 3 months among randomized AIS patients with pre-treatment NIHSS scores >=10 in the Combined Lysis of Thrombus in Brain Ischemia (CLOTBUST), Transcranial Ultrasound in Clinical Sonothrombolysis (TUCSON) and pilot randomized clinical safety study of sonothrombolysis with microspheres (Definity study). Patients had proximal arterial occlusions identified by baseline TCD and received intravenous (IV) tPA or IV tPA plus continuous 2-hour TCD ultrasound monitoring (=sonothrombolysis). Favorable outcome was defined as modified Rankin Scale (mRS) 0-1 at 3 months. Sustained complete recanalization was defined as Thrombolysis in Brain Ischemia (TIBI) flow grades 4-5 assessed by TCD at 2 hours after tPA bolus. Symptomatic intracranial hemorrhage (sICH) was defined using ECASS-2 definition as imaging evidence of ICH with clinical worsening (NIHSS >=4) within 72 hours from stroke onset. Results: A total of 139 AIS patients with severe stroke due to proximal arterial occlusions (mean age 69±13years, 56% men, median NIHSS 17, interquartile range 14-21, range 10-34) were randomized in CLOTBUST (n=105), TUCSON (n=21) and Definity (n=13). A total of 60 (43%) and 79 (57%) patients were randomized to IV tPA and sonothrombolysis, respectively. Patients treated with IV tPA and sonothrombolysis did not differ in terms of age, baseline stroke severity, baseline TIBI grades and onset-to-treatment time. Symptomatic ICH rates were similar in patients treated with IV tPA and sonothrombolysis (5.0% vs. 5.1%; p=0.987). More patients achieved sustained complete recanalization in the sonothrombolysis than in the IV tPA group (38.0% vs. 18.3%; p=0.012). Favorable outcome (mRS 0-1) tended to be more prevalent in the sonothrombolysis than in the IV tPA group (36.6% vs. 23.2%; p=0.104). Conclusions: Our data point to a signal-of-efficacy and provide basis to determine the sample size of a phase 3 randomized trial of sonothrombolysis in patients with severe strokes ( NCT01098981 ).