Mild Hypothermia After Endovascular Treatment for Acute Ischemic Stroke: A Pilot Randomized Controlled Trial

BACKGROUND: Therapeutic hypothermia is a potent neuroprotective therapy that mitigates ischemic brain injury. This study aimed to investigate the safety and feasibility of mild therapeutic hypothermia after successful endovascular recanalization in patients with acute ischemic stroke due to major vessel occlusion. METHODS: We conducted a prospective, multicenter, open-label pilot randomized clinical trial at 5 stroke centers in South Korea between December 2016 and November 2019. Patients with acute ischemic stroke who achieved successful recanalization within 8 hours of symptom onset were included. The participants were randomly assigned in a 1:1 ratio to receive either mild therapeutic hypothermia, targeted at 35 °C for 48 hours, or standard care. The primary objective was to assess feasibility and safety outcomes, including protocol adherence, achievement and maintenance of the target temperature, and adverse events related to the intervention. Exploratory efficacy outcomes included a modified Rankin Scale score of 0 to 2 at 3 months and neurological improvement (≥4-point reduction on the National Institutes of Health Stroke Scale score at discharge). Exploratory safety outcomes included mortality, hemorrhagic transformation, and any bleeding. RESULTS: Forty patients were enrolled in this study, with 20 patients in each group. The target temperature was successfully achieved and maintained in all patients of the mild hypothermia group in accordance with the intervention protocol. At 3 months, the mortality rates were 5% in the mild hypothermia group and 0% in the control group ( P =1). A modified Rankin Scale score of 0 to 2 was achieved in 70% and 65% of the mild hypothermia and control groups, respectively ( P =0.736). Few adverse events (bradycardia and rhabdomyolysis) were more frequent in the mild hypothermia group but were manageable. CONCLUSIONS: Mild hypothermia at 35 °C after successful recanalization via endovascular treatment in acute ischemic stroke is safe and feasible, despite some adverse events. This pilot study demonstrated that mild hypothermia is well tolerated in this patient population, and further study is needed to confirm its effectiveness. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02985060.