Selective intra-arterial cooling infusion with endovascular thrombectomy for acute ischemic stroke: a multicenter, randomized, controlled trial protocol and statistical analysis plan

INTRODUCTION: The cerebroprotective effects of hypothermia via selective intra-arterial cooling infusion (SI-AC) as an adjunct to endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO) are uncertain. This trial aims to determine the efficacy and safety of SI-AC in patients with anterior circulation LVO-AIS undergoing EVT. METHODS AND DESIGN: A multicenter, national, investigator-initiated and -conducted, randomized, controlled, and subject- and assessor-blinded superiority clinical trial conducted at 12 hospitals in China. Patients with anterior circulation LVO-AIS presenting within 24 hours of symptom onset are randomized 1:1 to receive SI-AC plus EVT (intervention) or EVT (control) in addition to standard care and be followed up for 90 days. Sample size estimates: Using a two-sided significance level of 0.05 and assuming a 5% loss of patients at follow-up, we estimate 258 patients provides 80% power to detect a common odds ratio of 1.9 for improved functional recovery, evaluated using the modified Rankin Scale (mRS) at 90 days. OUTCOMES: The primary outcome is mRS score distribution at 90 days. Secondary outcomes include different cut-points on the mRS (0-2 and 0-1) at 90 days, Barthel index scores at 90 days, infarct volume at 7 days, and early neurologic improvement at 24 hours. Safety outcomes include the incidence of symptomatic intracranial hemorrhage and any intracranial hemorrhage at 24 hours, procedure-related complications, and all-cause mortality at 90 days. CONCLUSION: This trial is designed to evaluate the efficacy and safety of SI-AC as a novel cerebroprotective strategy for patients with anterior circulation LVO-AIS undergoing EVT. TRIAL REGISTRATION: ClinicalTrials.gov (NCT06485427).