Innovative Application of Pressure Gradient Measurement in Internal Carotid Stenosis in Patients Undergoing CAS

Study Overview
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Brief Summary
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About 20% of stroke causes are atherosclerotic strokes caused by carotid artery stenosis. In 2005, 92% of carotid artery interventions in the USA were performed in asymptomatic patients. It should be noted that screening in the general population for carotid artery disease is unwarranted, due to uncertain eligibility criteria for interventional treatment of asymptomatic patients. On the other hand, 10-15% of all patients with a first-ever stroke will experience an ischemic stroke as a result of previously untreated, asymptomatic, significant carotid artery stenosis. Carotid artery angioplasty with stent placement (CAS) has become the second method of revascularization. ed, however, there is a great deal of ambiguity in the application of these criteria, which stems from the ratio of the risk to the possible benefit to the patient of performing the procedure, as well as the cost-effectiveness for health care systems. OBJECTIVES The overall goal is (following the model of measuring fractional flow reserve - FFR) to try to establish a new parameter that could prove helpful in qualifying patients for percutaneous internal carotid artery angioplasty with stent implantation (CAS). Determining whether measuring the pressure gradient across the stenosis will determine which patients will benefit from the CAS procedure. In the absence of convincing evidence on the effects of CAS, especially for so-called asymptomatic patients, it is advisable to establish a parameter that would complement the eligibility criteria that, on the one hand, could prevent strokes in the population of patients with silent internal carotid artery stenosis and, on the other hand, avoid performing the procedure in the absence of benefit. PRIMARY ENDPOINTS: Assessment of cerebral perfusion by computed tomography before and after CAS Assessment of cognitive symptoms using before and after CAS Assessment of neurological symptoms before and after CAS Evaluation of otolaryngological symptoms before and after CAS SECONDARY ENDPOINTS: Creation of a non-invasive computed tomography protocol with pressure gradient assessment in patients with carotid artery stenosis. A final version of the algorithm based on a new diagnostic measurement (concentration gradient) ready to be used in the diagnosis of CAS-eligible patients with an implemented function for automatic classification of measurement results that will indicate the group of patients who will benefit from the CAS procedure.

Detailed Description
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After qualification for the study (by a neurologist and vascular surgeon), patients meeting properly the inclusion and exclusion criteria will be referred for imaging studies with Doppler ultrasound and angio-CT scan of the arteries of the neck and head (concomitantly with assessment of cerebral perfusion). In addition, blood will be drawn and stored for subsequent testing. Afterwards, patients qualified for internal carotid artery angioplasty procedures will receive standard saturation treatment with two antiplatelet drugs (acetylsalicylic acid, clopidogrel) before the procedure, strictly according to the guidelines. The procedures are carried out with approved medical equipment (carotid stent, angioplasty balloon, peripheral neuroprotection). The selection of the appropriate equipment used for the procedure depends on the clinical situation, the experience of the operator and the anatomical conditions of the carotid arteries. Measurements (invasive pressure in carotid artery) taken during the procedure before angioplasty (after insertion of the neuroprotection into the internal carotid artery) and after stent implantation: COURSE OF THE STUDY Baseline examination: Doppler ultrasound of the extracranial cephalic arteries initial qualification for CAS /neurologist, vascular surgeon/ informed consent to participate in the study cardiological consultation (modification of risk factors) angio-CT of the neck and head with assessment of brain perfusion additional neurological (with questionnaires), psychological (with questionnaires) and otolaryngological examination surgery (CAS) - Department of Vascular Surgery, Department of Cardiology Measurements (invasive pressure) taken during the procedure before angioplasty (after insertion of the neuroprotection into the internal carotid artery) and after stent implantation: placement of a micro catheter to measure invasive pressure taking a measurement in the internal carotid artery above the stenosis (in the normal section of this artery) performing a measurement before the stenosis (in the normal segment of the common carotid artery at the level of the exit of the external carotid artery) reading the pressure gradient after obtaining a stable value (a minimum of 5 cardiac cycles) The study of intravascular pressure measurements will be performed using a special micro catheter of about 1mm in size (i.e., more than 2 times smaller than the delivery system for distal protection, which is the standard procedure, so the risk of complications is minimal). In the study protocol, the insertion of the catheter and measurement of pressures will be followed by the placement of a neuroprotection device in the distal carotid artery (standard of practice) to avoid possible complications. Evaluation during treatment: angio-CT of the neck and head with assessment of brain perfusion, 3 month after CAS Doppler ultrasound of the extracranial cephalic arteries, 3 and 12 month after CAS Neurological (with questionnaires), psychological (with questionnaires) and otolaryngological examination betwenn 10-16 week after CAS Cardiological evaluation at 3, 6, 12 month after CAS (modification of risk factors)

Official Title
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Evaluation of Diagnostic and Predictive Capabilities of Novel Application of Carotid Carotid Stenosis Pressure Gradient Measurement in Patients Undergoing Percutaneous Carotid Angioplasty and Stenting (CAS).

Conditions
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Carotid Artery Stenosis, Carotid Artery Stenting, Stroke

Intervention / Treatment
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* Procedure: CAS + Intravascular measuring the pressure gradient
* Procedure: CAS (standard)
* Diagnostic Test: Doppler ultrasonound of cephalic arteries
* Radiation: Angio-CT of the neck and head with assessment of brain perfusion
* Other: Otolaryngological examination
* Other: Psychological examination
* Other: Neurological examination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stenosis of the internal carotid artery in symptomatic patients: > 50%, (confirmed by non-invasive imaging studies: USG, angio-CT), qualified for angioplasty with stent implantation Stenosis of the internal carotid artery in asymptomatic patients: >60%, (confirmed by non-invasive imaging studies: USG, angio-CT), qualified for angioplasty with stent implantation Age of patients: > 18 years of age Provided informed consent to participate in the study. Exclusion Criteria: Inability to obtain informed consent to participate in the study. Difficult anatomy of the aortic arch and the descending cephalic arteries (increased atherosclerotic lesions, acute angle of departure of the common carotid arteries, kinking of the internal carotid arteries).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAS + Intravascular measuring the pressure gradient<br>Patients with internal carotid stenosis qualified for angioplasty with stent implantation. Standard CAS procedure with additional intravascular pressure measurements | Procedure: CAS + Intravascular measuring the pressure gradient<br>* Measurements taken during the procedure during CAS placement of a FFR- micro catheter on the neuroprotection wire and taking a measurement before the stenosis and in the internal carotid artery above the stenosis reading the pressure gradient after obtaining a stable value (a minimum of 5 cardiac cycles) the study of intravascular pressure measurements will be performed using a special micro catheter<br>Procedure: CAS (standard)<br>* Animation of blood pressure measurements on the FFR console without actual measurement in carotid artery (blinding of the study to the patient) during CAS procedure.<br>Diagnostic Test: Doppler ultrasonound of cephalic arteries<br>* non-invasive assessment of carotid stenosis before surgery and assessment of results after CAS (3 and 12 months after CAS)<br>Radiation: Angio-CT of the neck and head with assessment of brain perfusion<br>* Non-invasive pre-operative assessment and post-CAS result (3 months after) Brain perfusion: assesses the areas of the brain supplied with blood and provides information regarding blood flow to the brain<br>Other: Otolaryngological examination<br>* Hearing and balance tests (before and after CAS) - prospective follow-up<br>Other: Psychological examination<br>* psychological examination with questionnaires (before and after CAS) - prospective follow-up<br>Other: Neurological examination<br>* neurological examination with questionnaires (before and after CAS) - prospective follow-up<br>|
| Active Comparator: CAS (standard)<br>Patients with internal carotid stenosis qualified for angioplasty with stent implantation. Standard CAS procedure. | Procedure: CAS (standard)<br>* Animation of blood pressure measurements on the FFR console without actual measurement in carotid artery (blinding of the study to the patient) during CAS procedure.<br>Diagnostic Test: Doppler ultrasonound of cephalic arteries<br>* non-invasive assessment of carotid stenosis before surgery and assessment of results after CAS (3 and 12 months after CAS)<br>Radiation: Angio-CT of the neck and head with assessment of brain perfusion<br>* Non-invasive pre-operative assessment and post-CAS result (3 months after) Brain perfusion: assesses the areas of the brain supplied with blood and provides information regarding blood flow to the brain<br>Other: Otolaryngological examination<br>* Hearing and balance tests (before and after CAS) - prospective follow-up<br>Other: Psychological examination<br>* psychological examination with questionnaires (before and after CAS) - prospective follow-up<br>Other: Neurological examination<br>* neurological examination with questionnaires (before and after CAS) - prospective follow-up<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Predictive capabilities of the obtained invasive pressure gradient in carotid artery stenosis on changes in cerebral perfusion after surgery | Composite endpoint including: Assessment of the predictive capabilities of the obtained pressure gradient values on changes in cerebral perfusion after surgery (In the quantitative assessment of CT perfusion - blood flow and blood volume are determined and the mean transit time) | 12 months | 
| Predictive capabilities of the obtained invasive pressure gradient in carotid artery stenosis on neurological status | Composite endpoint including: - changes in neurological status (assesed by the MMSE, mini-mental state examination; NIHSS, National Institutes of Health Stroke Scale), | 12 months | 
| Predictive capabilities of the obtained invasive pressure gradient in carotid artery stenosis on mental status | Composite endpoint including: - changes in cognitive functions (assesed by the MOCA, Montreal Cognitive Assessment - test) | 12 months | 
| Predictive capabilities of the obtained invasive pressure gradient in carotid artery stenosis on otolaryngological status in hearing functions | Composite endpoint including: - changes in hearing functions (assesed by the audiometry, tympanometry and ipsilateral middle ear reflex, otoemission, Skarzynski Tinnitus Scale, ABR - Auditory Brainstem Response, BERA) | 12 months | 
| Predictive capabilities of the obtained invasive pressure gradient in carotid artery stenosis on otolaryngological status in labyrinth functions | Composite endpoint including: - changes in labyrinth functions (assesed by the Skarzynski Tinnitus Scale) | 12 months | 
| Predictive capabilities of the obtained invasive pressure gradient in carotid artery stenosis on MACEs after surgery | Composite endpoint including: - occurence of stroke/TIA or death | 12 months | 
| Repeatability the diagnostic possibilities of non-invasive tests (Doppler ultrasound) in invasive pressure gradient values | Composite endpoint including: - comparison of the obtained invasive pressure gradient values with Doppler ultrasound (PSV, peak systolic velocity; EDV, end-diastolic velocity; estimated degree of stenosis) | 12 months | 
| Repeatability the diagnostic possibilities of non-invasive tests (CT angiogram) in invasive pressure gradient values | Composite endpoint including: - comparison of the obtained invasive pressure gradient values with angio-CT: degree of stenosis | 12 months | 
| Repeatability the diagnostic possibilities of non-invasive tests (CT-FFR) in invasive pressure gradient values | Composite endpoint including: - comparison of the obtained invasive pressure gradient values with CT-FFR (planned creation of an algorithm based on test results: invasive pressure gradient, Doppler ultrasound, angio-CT) | 12 months | 
| Incidence of Treatment-Related Adverse Events [safety and tolerability] associated with the invasive intravascular pressure measurement procedure (1) | Composite endpoint including: - occurrence of periprocedural neurological event: TIA, stroke, death in patients who underwent CAS with the invasive intravascular pressure measurement procedure | 12 months | 
| Incidence of Treatment-Related Adverse Events [safety and tolerability] associated with the invasive intravascular pressure measurement procedure (2) | Composite endpoint including: - occurrence of another periprocedural complication: vascular spasm, perforation, cardiac arrhythmia, hypotonia/hypertension in patients who underwent CAS with the invasive intravascular pressure measurement procedure | 12 months | 
| Incidence of Treatment-Related Adverse Events [safety and tolerability] associated with the invasive intravascular pressure measurement procedure (3) | Composite endpoint including: - occurrence of new hypodense (impact) foci in the head CT scan after the procedure in patients who underwent CAS with the invasive intravascular pressure measurement procedure | 12 months | 
| Incidence of Treatment-Related Adverse Events [safety and tolerability] associated with the invasive intravascular pressure measurement procedure (4) | Composite endpoint including: - changes (improvement or deterioration) in brain perfusion (see point 1.) in the post-operative examination in patients who underwent CAS with the invasive intravascular pressure measurement procedure | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Algorithm angio-CT/non invasive pressure measurement in carotid | Creation a multiple regression model based on the data from non-invasive pre-procedural measurements on the incidence of unfavourable outcome measures. | 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAS (carotid artery stenting), FFR (fractional flow reserve), FFR-CT (Fractional Flow Reserve - Computed Tomography), Carotid Artery Stenosis, Functional assessment of the stenosis, Decision making algorithm