Internal Carotid Artery Stenosis Clinical Trial
Official title:
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 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 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 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 CAS.
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), 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, 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. T2TSE; 3. FLAIR; 4. 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 EPI sequence.
T2TSE: TR=4000/TE=99/ETL=9, FOV 230, FOV ph. 75%, matrix 256x256. FLAIR: 8050/112/ETL=21/2
conc., FOV 230, FOV ph. 76,6%, matrix 256x151. EPI-DWI: 4200/139/EPI f.=96/6 av., FOV 230,
FOV ph. 100%, phase enc. direction A-P, matrix 128x96 with interpolation, phase partial
Fourier 6/8, Bw 1346 Hz/Px, echo spacing 0.83 ms, TA. Sequence called "trace" with three
types of MR 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 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 UM 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.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00737334 -
EEG, Cerebral Oximetry, and Arterial to Jugular Venous Lactate to Assess Cerebral Ischemia During Carotid Endarterectomy
|
N/A | |
| Completed |
NCT02398734 -
SONOlysis in Prevention of Brain InfaRctions During Internal Carotid Endarterectomy
|
N/A | |
| Completed |
NCT02794974 -
Ultrasound-guided Intermediate Cervical Plexus Block
|
N/A | |
| Completed |
NCT01877174 -
MICHI™ Neuroprotection System (NPS+f) Filter Debris Analysis Study (The F-1 Study)
|
N/A | |
| Recruiting |
NCT03121209 -
Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial - Hemodynamics (CREST-H)
|
Phase 3 | |
| Recruiting |
NCT05260229 -
The Observation About the Effects of Internal Carotid Artery Stenosis on Fundus Vessels and the Changes of Fundus Vessels After Interventional Therapy
|