Clinical Trial: SONOlysis in Prevention of Brain InfaRctions During Internal Carotid Endarterectomy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Risk Reduction of Symptomatic and Silent Brain Infarctions During Carotid Endarterectomy by the Ultrasound Activation of Endogenous Fibrinolytic System Using Sonolysis (Tr

Brief Summary:

SONOBIRDIE Trial is a randomized, single-blind, sham-controlled study designed for a demonstration of the safety and effectiveness of sonolysis (continual transcranial Doppler monitoring) in reduction of risk of stroke or transient ischemic attack (TIA), brain infarctions and cognitive decline using a 2-MHz diagnostic probe with a maximal diagnostic energy on the reduction of risk of brain infarctions by the activation of endogenous fibrinolytic system during carotid endarterectomy (CEA) in patients with ≥ 70% symptomatic or asymptomatic internal carotid artery stenosis.

The sample size is based on an expected 2.5% reduction of stroke or TIA during the 30-day postoperative period in the sonolysis group (estimated prevalence, 1.5 %) compared to the control group (estimated prevalence, 4 %). Pre-study calculations showed that a minimum of 704 patients in each group is needed to reach a significant difference with an alpha value of 0.05 (two-tailed) and a beta value of 0.8 assuming that 10 % would be lost to follow-up or refuse to participate in the study.

Consecutive patients will be assigned to the sonolysis or control group by a computer-generated 1:1 randomization. In patients randomized into sonolysis group, middle cerebral artery segment in a depth of 55 mm will be continuously monitored during intervention using a diagnostic 2-MHz transcranial Doppler probe with a maximal diagnostic energy.

In patients randomized into control group, the transcranial Doppler probe will be fixed in a required position using a special helmet as in sonolysis group patients, but middle cerebral artery segment in a depth of 55 mm will be only localized using a diagnostic 2-MHz transcranial Doppler probe with a maximal diagnostic energy and the TCD monitoring will be stopped afterwards.<

Detailed Summary:

Stroke has been the third most common cause of death in the majority of the developed countries for many years. Internal carotid (ICA) stenosis is one of the most common etiological factors of ischemic stroke (IS), causing 10 - 35 % of strokes. Stroke risk increases with the increased severity of ICA stenosis and this risk is higher in symptomatic stenoses than in asymptomatic ones. Results of the NASCET, ECST and ACAS studies showed that carotid endarterectomy (CEA) was a beneficial therapy for patients with a symptomatic ICA stenosis > 50 % and > 70 %, resp., and for patients with an asymptomatic ICA stenosis > 60 % and > 85 %, resp. Surgical risk of CEA varied between 2 and 15 %. However, even clinically silent microembolism can cause microinfarctions presenting with postoperative cognitive deficit.

Since the 1970s, in vitro and in animal models studies demonstrated acceleration of thrombus dissolution using ultrasound beam. Alexandrov et al. referred a higher number of early recanalizations in acute stroke patients with middle cerebral artery (MCA) occlusion treated using systemic thrombolysis in combination with transcranial Doppler (TCD) monitoring. Between 2002 and 2005, three other studies demonstrated potential effect of diagnostic ultrasound on the acceleration of spontaneous or induced recanalization of intracranial arteries. There are 2 possible effects of ultrasound on thrombus - [1] mechanical destruction due to vibration of thrombus with acceleration of penetration of fibrinolytics into thrombus and [2] elevation of temperature and stimulation of endothelium with local activation of fibrinolytic system. The results of the grant project NR/9487-3/2007 showed that TCD monitoring had a significant effect on activation of fibrinolytic system in healthy volunteers.

Transcranial Doppler monitoring duri
Sponsor: University Hospital Ostrava

Current Primary Outcome: Occurence of stroke or transient ischemic attack [ Time Frame: 30 days after intervention ]

The incidence of stroke or transient ischemic attack during 30 days after the carotid endarterectomy in sonolysis and control groups


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Occurrence of death, any stroke, or myocardial infarction [ Time Frame: 30 days after intervention ]
    Occurrence of death, any stroke, or myocardial infarction within 30 days (myocardial infarction is defined as post-interventional cardiac troponin T level increase > 2 times the normal upper limit in addition to either chest pain, symptoms consistent with heart ischemia, or electrocardiographic evidence of ischemia)
  • Cognitive decline [ Time Frame: 1 year after intervention ]
    Changes in cognitive functions as evidenced by Addenbrooke's Cognitive Examination Revised, Mini Mental State Examination, Clock Drawing Test, or Verbal Fluency Test scores 1 year post-procedure relative to pre-treatment scores
  • Occurence of new ischemic lesions ≥ 0.5 mL on brain DWI-MRI (Substudy) [ Time Frame: 24 hours after intervention ]
    Number of new lesions and occurrence of new lesions ≥ 0.5 mL on post-procedural brain DWI-MRI
  • Occurence of ipsilateral new ischemic lesions on brain DWI-MRI (Substudy) [ Time Frame: 24 hours after intervention ]
    Incidence of ipsilateral new ischemic lesions on post-procedural brain DWI-MRI
  • Adverse events [ Time Frame: 30 days after intervention ]
    Summary of any adverse events


Original Secondary Outcome:

  • Occurrence of death, any stroke, or myocardial infarction [ Time Frame: 30 days after intervention ]
    Occurrence of death, any stroke, or myocardial infarction within 30 days (myocardial infarction is defined as post-interventional cardiac troponin T level increase > 2 times the normal upper limit in addition to either chest pain, symptoms consistent with heart ischemia, or electrocardiographic evidence of ischemia)
  • Cognitive decline [ Time Frame: 1 year after intervention ]
    ] Changes in cognitive functions as evidenced by Mini Mental State Examination, Clock Drawing Test, or Verbal Fluency Test scores 1 year post-procedure relative to pre-treatment scores
  • Occurence of new ischemic lesions ≥ 0.5 mL on brain DWI-MRI (Substudy) [ Time Frame: 24 hours after intervention ]
    Number of new lesions and occurrence of new lesions ≥ 0.5 mL on post-procedural brain DWI-MRI
  • Occurence of ipsilateral new ischemic lesions on brain DWI-MRI (Substudy) [ Time Frame: 24 hours after intervention ]
    Incidence of ipsilateral new ischemic lesions on post-procedural brain DWI-MRI
  • Adverse events [ Time Frame: 30 days after intervention ]
    Summary of any adverse events


Information By: University Hospital Ostrava

Dates:
Date Received: March 20, 2015
Date Started: October 2015
Date Completion: January 2023
Last Updated: April 11, 2017
Last Verified: April 2017