Adjuvant Systemic Hypothermia During Mechanical Thrombectomy (ReCCLAIM II): A Multicenter, Randomized, Controlled Trial

BACKGROUND: Hypothermia reduces ischemic injury in preclinical stroke models, yet translation into the clinical setting remains challenging. We aimed to assess the feasibility of inducing adjuvant systemic hypothermia among patients with large-vessel occlusion stroke during mechanical thrombectomy. METHODS: This was a phase II randomized feasibility-controlled trial involving 10 sites in the United States, conducted between May 2019 and May 2024. All eligible patients had confirmed proximal middle cerebral artery or internal carotid artery occlusions, an Alberta Stroke Program Early Computed Tomography Score of 6 to 10, and symptom onset within 24 hours. Patients underwent mechanical thrombectomy and were randomly assigned to either treatment with adjuvant hypothermia using a novel intravascular cooling catheter or standard of care. The primary feasibility end points were the ability to achieve a target temperature of <34 °C within 1 hour of arterial puncture and overall door-to-reperfusion times. The primary safety end point was core-laboratory-adjudicated hemorrhagic conversion within 36 hours, and secondary end points included final infarct volume and serious adverse events. RESULTS: A total of 95 patients were enrolled (29 in the roll-in phase and 66 randomized). The mean age of the randomized cohort was 65±12 years, with a median National Institutes of Health Stroke Scale score of 15. Among patients in the treatment arm, 30 of 33 (91%) achieved hypothermia within 1 hour of arterial puncture during thrombectomy, and 23 of 33 (70%) patients were at target temperature (<34 °C) before reperfusion. The median time to hypothermia was 10 minutes (interquartile range [IQR], 7–22) from arterial puncture. There were no significant differences in door-to-reperfusion times (hypothermia: 95 minutes [IQR, 54–116] versus control: 94 minutes [IQR, 77–121]; P =0.70). Final infarct volumes were numerically lower in the hypothermia treatment arm (hypothermia: 11 cm 3 [IQR, 5–42] versus control: 30 cm 3 [IQR, 6–80]; P =0.13), with no significant differences in the rates of hemorrhagic conversion or pneumonia. There was a higher number of serious adverse events in the hypothermia arm (45.5% versus 24.2%; P =0.12), although the trial was not powered for differences in serious adverse events or clinical efficacy. CONCLUSIONS: This is the first clinical trial to demonstrate the feasibility of early and rapid systemic hypothermia as an adjunct therapy during mechanical thrombectomy without delaying time to reperfusion. The potential impact on infarct volumes and serious adverse events, however, warrants further investigation. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03804060.