Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT02360137 |
| Other study ID # |
15-29410A |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 1, 2015 |
| Est. completion date |
June 1, 2026 |
Study information
| Verified date |
July 2023 |
| Source |
University Hospital Ostrava |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Atherosclerosis is the most common cause of stroke. The aims of the project are to compare
the visual and digital analysis of sonographic images of atherosclerotic plaque in carotids
in vivo, in vitro and with a histological composition of the plaque obtained from patients
indicated to carotid endarterectomy, to compare the characteristics of symptomatic and
asymptomatic atherosclerotic plaques and, subsequently to verify a hypothesis that ultrasound
can identify the sonographic plaque characteristics associated with an increased risk of
plaque progression and of ischemic stroke (unstable plaque) in patients with carotid
atherosclerosis. Identifying of the sonographic characteristics of unstable plaque will allow
to improve indication criteria for carotid endarterectomy or stenting and also potential
changing of a drug therapy in patients with unstable plaque in the future. Cost efficiency
and availability of duplex ultrasound equipment may enable to improve diagnosis of unstable
plaque using this new plaque characteristics evaluation in the majority of patients with
carotid plaques.
Description:
Objectives and aims The objective of the project is to identify measurable features of
atherosclerotic plaque in carotids associated with plaque progression and increased
stroke/TIA risk using duplex sonography and digital B-mode image analysis.
The project aims
1. to identify characteristics of carotic atherosclerotic plaque in ultrasound B-mode
associated with a risk of progression or stroke/TIA onset - the "vulnerable"
atherosclerotic plaque using
1. visual assessment
2. digital image analysis using a computer program
2. to determine the correlation of the ultrasound finding of carotic atherosclerotic plaque
in a B-mode in vivo (before endarterectomy) and subsequently in vitro (after
endarterectomy) in patients indicated to carotid endarterectomy using
1. visual assessment
2. digital image analysis using a computer program
3. to assess a correlation between histological evaluation of composition of
atherosclerotic plaque obtained during carotid endarterectomy and ultrasound image of
atherosclerotic plaque in a B-mode in vitro using
1. visual assessment
2. digital image analysis using a computer program
4. to compare histological and ultrasound findings in vitro and in vivo between
asymptomatic and symptomatic atherosclerotic plaques in the carotid bifurcation using
1. visual assessment
2. digital image analysis using a computer program
5. to compare the features of asymptomatic and symptomatic atherosclerotic plaque in the
carotid bifurcation using
1. sonographic perfusion examination of plaque in vivo (after application of
echocontrast agent)
2. elastography
The grant project is in concordance with the scope, expected benefits, key objective of the
Programme "Ensuring internationally comparable levels of healthcare research and use the
results to improve the health of Czech population and to secure the current needs of the
health sector in the Czech Republic" and the sub-objective 1.2.2. "The development of early
diagnosis of cardiovascular and cerebrovascular disease and finding treatment modalities and
procedures in the treatment of cardiovascular and cerebrovascular disease with greater
therapeutic efficiency and greater parsimony for the patient."
Project design
1. Patients The project period will take 132 months. Total of 1863 patients with
atherosclerotic plaques in the carotid bifurcation and internal carotid artery causing
arterial stenosis ≥ 30% detected by duplex sonography will be included to the study.
Patients indicated for carotid intervention according to the currently valid guidelines
(American Heart Association/American Stroke Association [AHA], European Stroke
Organisation [ESO]) will undergo carotid endarterectomy or carotid stenting. Patients
will be screened and enrolled in sonographic laboratories of the Military University
Hospital in Prague, Na Homolce Hospital Prague, University Hospital Ostrava, Olomouc and
Hradec Kralove.
Inclusion criteria: 1/ age 30 - 90 years, 2/ sufficient image quality of atherosclerotic
plaque in the carotid bifurcation and ICA using ultrasound, 3/ independency of the
patient (0 - 2 points in the modified Rankin scale), 4/ signed informed consent.
Exclusion criteria: 1/ serious disease with a low probability of survival of at least 3
years, 2/ other objective obstacles preventing regular 6-month ultrasound scan.
Clinical examination: Physical and neurological examinations and examinations of carotid
arteries by duplex sonography will be performed in all patients at baseline and every 6
months for 3 years.
2. Sample size calculation The sample size for prospective follow-up of atherosclerotic
plaques was based on an expected 5% difference in stroke risk between plaque
characteristics. Pre-study calculations showed that a minimum of 1863 patients were
needed to reach a significant difference with an alpha value of 0.05 (two-tailed) and a
beta value of 0.8 assuming that 20 % of subjects will lost to follow-up.
The sample size for patients undergoing carotid endarterectomy with subsequent in vitro
sonographic and histological evaluation of atherosclerotic plaques was based on an
expected Spearman's correlation coefficient ≥ 0.3 between histological and sonographic
evaluation of atherosclerotic plaque (visual and digital image analysis). Pre-study
calculations showed that a minimum of 152 patients were needed to reach a significant
difference with an alpha value of 0.01 (after Bonferroni correction for 5 evaluated
factors) and a beta value of 0.8 assuming that 20 % of plaques will not be suitable for
evaluation.
3. Duplex sonographic examination of carotid arteries Standard duplex sonography of
cervical vessels focusing on the carotid bifurcation and proximal part of the ICA with
measurement of the maximum width of atherosclerotic plaque and transcranial duplex
color-coded sonography will be performed in all all patients at baseline and thereafter
in 6-month period for 3 years (totally 7 examinations). Examinations will be performed
using high-end duplex ultrasound system ESAOTE MyLab Twice (ESAOTE, Genova, Italy) with
linear probe LA435 (10 - 18 MHz), vascular preset, scanning depth 4.0 cm, 2 focuses in
2.0 and 3.0 cm; for transcranial duplex sonography, a phase array PA 240 (2 - 4 MHz)
will be used. Free hand sonographic scanning will be performed in B-mode in longitudinal
and transversal planes (continuous hand moving without changes of probe angle). Video
sequences from both longitudinal and transversal scanning and images of cross-section of
the plaque in subsequent distance of 0.5 mm will be saved and encoded. Visual
characteristics of the plaque (echogenicity, homogeneity, surface, etc.) and digital
image analysis using B-mode Assist System will be performed from each video sequence and
each cross-section of the plaque. Sonographic examination of plaque perfusion in vivo
after application of echocontrast agent (SonoVue, Bracco, Italy) and elastography will
be performed in at least 25 patients.
4. Carotid endarterectomy Surgery will be undertaken according to standard protocols using
general anesthesia in all patients at both centers (with > 400 carotid endarterectomies
carried out during the last 5 years). All patients will be on uninterrupted long-term
acetylsalicylic acid therapy (100 mg/day) or dual antiplatelat therapy during the
perioperative period. A dose of 100 IU per 1 kg of body weight of unfractionated heparin
(Heparin Léčiva, Zentiva, k.s., Prague, Czech Republic) will be administered routinely
at least 3 - 5 min before flow arrest in carotid artery. The plaque in carotid
bifurcation and proximal part of the ICA will be removed as a 1 block from the artery.
Protamin (Protamin Meda-Ampullen, Legacy Pharmaceuticals Switzerland GmbH, Birsfelden,
Switzerland) in a dose of 1 mL per 2,000 IU of unfractionated heparin will be
administered 5 min after flow restoration in the ICA when needed. Clopidogrel (Trombex
75 mg, Zentiva, k.s., Prague, Czech Republic) will be administered 5 days after surgery
(75 mg/day) when indicated.
5. Sonographic examination of atherosclerotic plaque in vitro All atherosclerotic plaques
obtained during endarterectomy as a 1 block will be examined sonographically in vitro.
Examination will be performed using the high-end duplex ultrasound system ESAOTE MyLab
Twice (ESAOTE, Genova, Italy) with linear probe LA435 (10-18 MHz), vascular preset,
scanning depth 2.0 cm, 2 focuses in 1.0 and 2.0 cm. Atherosclerotic plaques extracted
from carotid arteries will be transported in a box with formaldehyde. Each plaque will
be inserted to the open plastic box filled by HAES 130/04 Voluven solution (colloid
plasma expander). Free hand sonographic scanning will be performed in B-mode in
longitudinal and transversal planes (continuous hand moving without changes of probe
angle). Video sequences from both longitudinal and transversal scanning and images of
cross-section of the plaque in subsequent distance of 0.5 mm will be saved and encoded.
Visual characteristics of the plaque (echogenicity, homogeneity, surface, etc.) and
digital image analysis using B-mode Assist System will be performed from each video
sequence and each cross-section of the plaque.
6. Histological processing and analysis of atherosclerotic plaque All atherosclerotic
plaques obtained during endarterectomy as a 1 block will be processed and analysed
histologically after sonographic examination. Visual characteristics of the plaque and
digital image analysis using B-mode Assist System will be performed from each
cross-section of the plaque.
