OBJECTIVE: To evaluate the effectiveness and safety of sonolysis using a low intensity 2 MHz pulsed wave ultrasound beam during carotid endarterectomy. DESIGN: Multicentre, phase 3, double blind, randomised controlled trial. SETTING: 16 European centres. PARTICIPANTS: 1004 patients (mean age 68 years; 312 (31%) female) were enrolled in the study between 20 August 2015 and 14 October 2020 until the interim analysis was performed. INTERVENTIONS: Sonolysis (n=507) versus sham procedure (n=497). MAIN OUTCOME MEASURES: The primary endpoint was the composite incidence of ischaemic stroke, transient ischaemic attack, and death within 30 days. The incidence of new ischaemic lesions on follow-up brain magnetic resonance imaging was the main substudy endpoint, and incidence of intracranial bleeding was the main safety endpoint. RESULTS: The results favoured the sonolysis group for the primary endpoint (11 (2.2%) v 38 (7.6%); risk difference -5.5%, 95% confidence interval (CI) -8.3% to -2.8%; P<0.001), as well as in the substudy for magnetic resonance imaging detected new ischaemic lesions (20/236 (8.5%) v 39/224 (17.4%); risk difference -8.9%, -15% to -2.8%; P=0.004). Sensitivity analysis resulted in a risk ratio for sonolysis of 0.25 (95% CI 0.11 to 0.56) for ischaemic stroke and 0.23 (0.07 to 0.73) for transient ischaemic attack within 30 days. Sonolysis was found to be safe, and 94.4% of patients in the sonolysis group were free from serious adverse events 30 days after the procedure. CONCLUSION: Sonolysis was safe for patients undergoing carotid endarterectomy and resulted in a significant reduction in the composite incidence of ischaemic stroke, transient ischaemic attack, and death within 30 days. TRIAL REGISTRATION: Clinicaltrials.gov NCT02398734.

• MeSH
• Double-Blind Method MeSH
• Ischemic Stroke epidemiology   prevention & control   etiology   MeSH
• Endarterectomy, Carotid * methods   adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Aged MeSH
• Carotid Stenosis * surgery   therapy   MeSH
• Ischemic Attack, Transient epidemiology   etiology   prevention & control   MeSH
• Ultrasonic Therapy * methods   adverse effects   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Geographicals
• Europe epidemiology   MeSH