SONOlysis in Prevention of Brain Infarctions dUring Carotid Stenting and caroTid EndaRterectomy (SONOBUSTER)
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|ClinicalTrials.gov Identifier: NCT01591005|
Recruitment Status : Completed
First Posted : May 3, 2012
Results First Posted : September 8, 2016
Last Update Posted : September 8, 2016
|First Submitted Date ICMJE||April 23, 2012|
|First Posted Date ICMJE||May 3, 2012|
|Results First Submitted Date||December 22, 2015|
|Results First Posted Date||September 8, 2016|
|Last Update Posted Date||September 8, 2016|
|Study Start Date ICMJE||October 2010|
|Actual Primary Completion Date||July 2014 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Participants With a New Brain Infarction Detected Using Magnetic Resonance [ Time Frame: 24 hours after intervention ]
The number of participants with a new brain infarctions in sonolysis group detected using magnetic resonance examination 24 hours after carotid endarterectomy or carotid stenting.
Substudy: The number of participants with a new brain infarctions on brain diffusion-weighted magnetic resonance imaging performed 24 hours after intervention in carotid endarterectomy and carotid stenting groups.
|Original Primary Outcome Measures ICMJE
||New brain infarction detected using MRI [ Time Frame: 24 hours after intervention ]
The twenty-percent risk reduction of number and volume of brain infarctions and brain infarctions > 0.5 cm3 in sonolysis group detected using MRI examination 24 hours after CEA or CS in 5% level of statistical significance
|Change History||Complete list of historical versions of study NCT01591005 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Outcome Measures ICMJE
||Number of Participants With Complications [ Time Frame: 24 hours and 30 days after intervention ]
Any complication during carotid endarterectomy and carotid stenting, sonolysis or 30 days after intervention in all subgroups.
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||SONOlysis in Prevention of Brain Infarctions dUring Carotid Stenting and caroTid EndaRterectomy|
|Official Title ICMJE||Risk Reduction of Symptomatic and Silent Brain Infarctions During Carotid Endarterectomy and Carotid Stenting Due to Ultrasound Activation of Endogenous Fibrinolytic System Using Transcranial Doppler Monitoring|
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% difference of new ischemic lesions on DWI-MRI between CEA (estimated prevalence, 30%) and CAS (54%). Pre-study calculations showed that a minimum of 73 patients in each group was needed to reach a significant difference with an alpha value of 0.05 (two-tailed) and a beta value of 0.8 assuming that 15% of subjects would be lost to follow-up or refuse to participate in the study.
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 computer generated random allocation will be used, separately for CEA and CS patients.
Substudy "Risk of brain infarction after carotid endarterectomy and stenting" Minimally146 patients with ICA stenosis >70% (symptomatic or asymptomatic) detected by duplex sonography and confirmed using computed tomography angiography (CTA); indication for carotid intervention (CEA or CAS) according to criteria set by the American Heart Association5; age 40-80 years; (iv) functionally independent (modified Rankin score 0-2 points); no contraindication to magnetic resonance imaging (MRI), computer tomography angiography (CTA) or digital angiography (DSA) will be enrolled to the Substudy.
Randomization: Randomization using computer generated random allocation to CEA or CS will be used.
Sonothrombolysis: In patients randomized into sonothrombolysis subgroup, middle cerebral artery (MCA) segment in depth 55 mm will be monitored for 40 minutes using a diagnostic 2 MHz probe with maximal diagnostic energy. Non-diagnostic TCD monitoring will be performed without detection of microembolic signals or detection of changes in blood flow. The second (control) subgroup will undergo a standard CEA or CS without sonothrombolysis.
MRI protocol will consists of 4 sequences: 1. Localizer; 2. T2-weighted images (T2TSE); 3. fluid-attenuated inversion recovery (FLAIR); 4. diffusion-weighted imaging (DWI). Sequences 1-3 will be applied in the same level, they will have the same slice thickness and the same cut number. The slice thickness comprises its own cut thickness (5 mm) + distant factor (30%). Standard number of slices is 19. Standard slice level is considered to be a modified level of skull base due to the minimalization of distant artifacts echo planar imaging (EPI) sequence. Sequence called "trace" with three types of magnetic resonance pictures in every slice: (a) T2*EPI b=0; (b) DWI b=500; (c) DWI b=1000. The fourth type of images automatically created an apparent diffusion coefficient (ADC) map (in-line postprocessing). DWI show a middle (average) diffusivity of every point of examined brain tissue when b value is 500 and 1000. This sequence is applied in order to assess hemorrhage (T2*EPI) and monitor sites of reduced diffusion (DWI, b=500 and 1000). New infarctions will be evaluated only in the territory of treated ICA.
Adverse effects: All adverse effects during 1 month after ultrasound monitoring will be registered, especially all causes for new admissions to the hospital, worsening of neurological symptoms (>4 points in NIH stroke scale), brain edema, symptomatic and asymptomatic intracranial bleeding detected in control brain MRI.
Statistic evaluation: All statistical tests will be performed at the Department of Biophysics, Informatics and Biometry, Palacký University Medical School, Olomouc. Statistical evaluation in 5% level of significance of differences in the number and volume of brain infarctions detected using MRI between patients with TCD monitoring and without TCD monitoring during CEA or CS will be performed using Student T-test, χ2-test, Mann-Whitney U-test, ANOVA and multivariate analysis. Differences in the number and volume of brain infarctions between patients after CEA and CS will be evaluated as secondary end-points. Influence of other factors, e.g. age, gender, symptoms in the territory of treated artery, number of infarctions before CEA or CS, results of cognitive tests will be evaluated.
Statistic evaluation for Substudy: The normality of distribution of all data will be checked using the Shapiro-Wilk test. Categorical variables in the two arms will be compared by Fisher's exact test. Continuous variables will be compared by the Student's t-test for normally distributed values and by Mann-Whitney U test for other values. Multiple logistic regression analyses were used to determine the possible predictors of a new brain infarction. All tests were carried out at an alpha level of significance of 0.05.
Study protocol has been approved by the Ethics Committees in accordance with the principles and guidelines of the Declaration of Helsinki, 1975.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
|Condition ICMJE||Internal Carotid Artery Stenosis|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Actual Study Completion Date||June 2015|
|Actual Primary Completion Date||July 2014 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||40 Years to 80 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Czech Republic|
|Removed Location Countries|
|NCT Number ICMJE||NCT01591005|
|Other Study ID Numbers ICMJE||NT11386-5/2010|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||
|Responsible Party||Vaclav Prochazka, MD, PhD. MSc, University Hospital Ostrava|
|Study Sponsor ICMJE||University Hospital Ostrava|
|Collaborators ICMJE||Palacky University|
|PRS Account||University Hospital Ostrava|
|Verification Date||July 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP