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 aimed to determine the efficacy and safety of SI-AC in patients with anterior circulation LVO-AIS undergoing EVT. Methods: A multicenter, national, investigator-initiated and -conducted, randomized, controlled, and subject- and assessor-blinded superiority clinical trial was conducted at 12 hospitals in China. Patients with anterior circulation LVO-AIS presenting within 24 h 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. 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. 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 h. Safety outcomes include the incidence of symptomatic intracranial hemorrhage and any intracranial hemorrhage at 24 h, 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.