Clinical Trial: SONOlysis in Prevention of Brain Infarctions dUring Carotid Stenting and caroTid EndaRterectomy

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Risk Reduction of Symptomatic and Silent Brain Infarctions During Carotid Endarterectomy and Carotid Stenting Due to Ultrasound Activation of Endogenous Fibrinolytic Syste

Brief Summary:

The aim of the project is to demonstrate a fibrinolytic effect of sonothrombolysis (continual transcranial Doppler monitoring) using 2 MegaHertz (MHz) diagnostic probe on the reduction of risk of brain infarctions due to the activation of endogenous fibrinolytic system during carotid endarterectomy (CEA) and carotid stenting (CS). 240 patients indicated for CEA (120 patients) and CS (120 patients) will be enrolled into the study in order to demonstrate a twenty-percent risk reduction of number and volume of brain infarctions detected using MRI examination 24 hours after CEA or CS in 5% level of significance. Patients will be randomized - subgroup 1 will undergo a 60minute non-diagnostic transcranial Doppler (TCD) monitoring during CEA or CS, subgroup 2 will undergo interventions without TCD monitoring. The second aim is to compare number of brain infarctions detected using MRI between CEA and CS patients.

Confirmation of the investigators hypothesis that sonothrombolysis is able to activate endogenous fibrinolytic system during CEA or CS with consecutive reduction of the number and volume of brain infarcts, can lead to the increase of the safety of CEA and CS in patients with internal carotid artery stenosis. The investigators can presume that up to 50% of patients indicated for CEA or CS can be treated using these methods in the future.

In the Substudy "Risk of brain infarction after carotid endarterectomy and stenting" the the risk of asymptomatic and symptomatic brain infarctions, changes in cognitive functions, as well as morbidity and mortality at 30 days between patients with symptomatic and asymptomatic severe internal carotid artery (ICA) stenoses undergoing elective CEA and CAS will be compared.

The sample size of the Substudy was based on an expected 80%

Detailed Summary:

AIM OF THE PROJECT AND HYPOTHESIS The aim of the project is to demonstrate an effect of continual TCD monitoring using 2 MHz diagnostic probe with maximal diagnostic energy on the reduction of risk of brain microinfarctions due to the activation of endogenous fibrinolytic system during CEA and CS. The second aim of the study is to compare the risk of brain infarction between CEA and CS.

240 patients indicated for CEA (120 patients) and CS (120 patients) will be enrolled into the study in order to demonstrate a twenty-percent risk reduction of number and volume of brain infarctions detected using MRI examination 24 hours after CEA or CS in 5% level of statistical significance. Patients will be randomized into 2 subgroups. Subgroup 1 will undergo a 60minute non-diagnostic TCD monitoring during CEA or CS. Subgroup 2 will undergo CEA or CS without TCD monitoring. The second aim is to compare number and volume of brain infarctions detected using MRI between CEA and CS patients.

Substudy "Risk of brain infarction after carotid endarterectomy and stenting" The aim of the prospective, randomized study was to compare the risk of asymptomatic and symptomatic brain infarctions, changes in cognitive functions, as well as morbidity and mortality at 30 days between patients with symptomatic and asymptomatic severe ICA stenoses undergoing elective CEA and CS.

PATIENTS AND METHODS 240 patients with ICA stenosis indicated for CEA or CS according to the criteria of the American Heart Association will be enrolled into the study during a 4-year period. Altogether 120 patients indicated for CEA and 120 patients indicated for CS will be randomized for standard CEA / CS and TCD monitored CEA / CS.

Randomization: Randomization using compu
Sponsor: University Hospital Ostrava

Current Primary Outcome: Participants With a New Brain Infarction Detected Using Magnetic Resonance [ Time Frame: 24 hours after intervention ]

Original Primary Outcome: New brain infarction detected using MRI [ Time Frame: 24 hours after intervention ]

Current Secondary Outcome:

• Participants With a New Brain Infarctions Detected Using Magnetic Resonance in Endarterectomy and Stenting Groups [ Time Frame: 24 hours after intervention ]

  The number of participants with a new brain infarctions >0.5 cm3 detected using magnetic resonance examination 24 hours after intervention between endarterectomy and stenting using periprocedural sonolysis.

  Substudy: The number of participants with a new brain infarctions >0.5 cm3 detected using magnetic resonance examination 24 hours after intervention between carotid endarterectomy and carotid stenting groups.

• Cognitive Decline [ Time Frame: 24 hours after intervention ]

  The changes in cognitive functions after carotid endarterectomy and carotid stenting measured by Mini-Mental State Examination using periprocedural sonolysis.

  Substudy: The changes in cognitive functions after intervention measured by Mini-Mental State Examination between carotid endarterectomy and carotid stenting groups.

  Range of scores possible for the Mini-Mental State Examination: 0 - 30 points. Higher values in this range are considered to be a better outcome.

• Number of Participants With Clinical Manifested Brain Infarction [ Time Frame: 24 hours and 30 days after intervention ]

  The risk of stroke or transient ischemic attack (at 24 hours and 30 days) due to the activation of endogenous fibrinolytic system during carotid endarterectomy and carotid stenting using periprocedural sonolysis.

  Substudy: The risk of stroke or transient ischemic attack (at 24 hours and 30 days) due to the activation of endogenous fibrinolytic system between carotid endarterectomy and carotid stenting groups.

• Number of Participatns With New Ipsilateral Brain Infarctions Detected Using MRI in Endarterectomy and Stenting Groups [ Time Frame: 24 hours after intervention ]

  The number of patients with the ipsilateral brain infarctions detected using MRI examination 24 hours after intervention between endarterectomy and stenting using periprocedural sonolysis.

  Substudy: The number of patients with the ipsilateral brain infarctions detected using MRI examination 24 hours after intervention between carotid endarterectomy and carotid stenting groups.

• Number of Participants With Clinical Vascular Event or Death [ Time Frame: 30 days after intervention ]

  The risk of the occurrence of death, any stroke, or myocardial infarction within 30 days (myocardial infarction was defined as a post-interventional cardiac troponin T level increase >2-fold the upper limit of normal in addition to either chest pain or symptoms consistent with ischemia or electrocardiographic evidence of ischemia) after carotid endarterectomy and carotid stenting using periprocedural sonolysis.

  Substudy: The risk of the occurrence of death, any stroke, or myocardial infarction within 30 days (myocardial infarction was defined as a post-interventional cardiac troponin T level increase >2-fold the upper limit of normal in addition to either chest pain or symptoms consistent with ischemia or electrocardiographic evidence of ischemia) between carotid endarterectomy and carotid stenting groups.

Original Secondary Outcome:

• New brain infarctions detected using MRI in endarterectomy and stenting groups [ Time Frame: 24 hours after intervention ]
  The number and volume of brain infarctions and brain infarctions >0.5 cm3 detected using MRI examination 24 hours after intervention between endarterectomy and stenting
• Cognitive Decline [ Time Frame: 24 hours after intervention ]
  The reduction of cognitive decline after CEA and CS measured by ADAS, MMSE, Clock Drawing Test and Verbal Fluency Test using periprocedural sonolysis
• Clinical manifested brain infarction [ Time Frame: 24 hours and 30 days after intervention ]
  The reduction of risk of clinically stroke due to the activation of endogenous fibrinolytic system during CEA and CS using periprocedural sonolysis

Information By: University Hospital Ostrava

Dates:
Date Received: April 23, 2012
Date Started: October 2010
Date Completion:
Last Updated: July 24, 2016
Last Verified: July 2016