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

Stroke Clinical Trial

— NOTICE-CAS  

Official title:

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).

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06123767
• Other study ID #: ABM/2023/01/00001
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 1, 2024
• Est. completion date: July 31, 2027

Study information

• Verified date: March 2024
• Source: 4th Military Clinical Hospital with Polyclinic, Poland
• Contact: Krzysztof Sciborski, MD, PhD
• Phone: 0048261660452
• Email: ksciborski[@]4wsk.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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:

1. Assessment of cerebral perfusion by magnetic resonanse before and after CAS

2. Assessment of cognitive symptoms using before and after CAS

3. Assessment of neurological symptoms before and after CAS

4. Assessment 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.

Description:

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, angio-CT scan of the arteries of the neck and head and cerebral perfusion in magnetic resonanse (assessment of the cerebral perfusion alterations using DSC (dynamic susceptibility contrast).

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

• assessment of the cerebral perfusion alterations using DSC (dynamic susceptibility contrast) MR 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, 3 month after CAS

• assessment of the cerebral perfusion alterations using DSC (dynamic susceptibility contrast) MR 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)

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: July 31, 2027
• Est. primary completion date: July 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Carotid Artery Stenosis
• Carotid Artery Stenting
• Carotid Stenosis
• Constriction, Pathologic
• Stroke

Intervention

Procedure:
• CAS + Intravascular measuring the pressure gradient
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
• CAS (standard)
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.

Diagnostic Test:
• Doppler ultrasonound of cephalic arteries
non-invasive assessment of carotid stenosis before surgery and assessment of results after CAS (3 and 12 months after CAS)

Radiation:
• Angio-CT of the neck and head
Non-invasive pre-operative assessment and post-CAS result (3 months after)

Other:
• Otolaryngological examination
Hearing and balance tests (before and after CAS) - prospective follow-up
• Psychological examination
psychological examination with questionnaires (before and after CAS) - prospective follow-up
• Neurological examination
neurological examination with questionnaires (before and after CAS) - prospective follow-up

Diagnostic Test:
• MR cerebral perfusion
Assessment of the cerebral perfusion alterations using DSC (dynamic susceptibility contrast) MR perfusion, before and after CAS (after 3 months): Parametric maps of cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), and mean transit time (MTT) will be generated and used for the qualitative and quantitative analyses of the following perfusion parameters: cerebral blood volume (CBV) value in ml/100ml; cerebral blood flow (CBF) value in ml/100ml/min; mean transit time (MTT) value in seconds time to peak (TTP) value in seconds

Locations

Country	Name	City	State
Poland	4th Military Hospital	Wroclaw	Dolnoslaskie

Sponsors (2)

Lead Sponsor	Collaborator
4th Military Clinical Hospital with Polyclinic, Poland	Medical Research Agency, Poland

Country where clinical trial is conducted

Poland, 

References & Publications (21)

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Min JK, Taylor CA, Achenbach S, Koo BK, Leipsic J, Norgaard BL, Pijls NJ, De Bruyne B. Noninvasive Fractional Flow Reserve Derived From Coronary CT Angiography: Clinical Data and Scientific Principles. JACC Cardiovasc Imaging. 2015 Oct;8(10):1209-1222. doi: 10.1016/j.jcmg.2015.08.006. — View Citation

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* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 (assessment of the cerebral perfusion alterations using DSC (dynamic susceptibility contrast) MR perfusion, before and after CAS	3 months
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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