99m Tc-ANNexin-V-128 Scintigraphy for the Identification of Complicated Carotid Atherosclerotic Plaques (ANNICA)
Primary Purpose
Carotid Atherosclerosis, Atherosclerotic Plaque
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
99mTc-Annexin-V-128 uptake on scintigraphy
Sponsored by
About this trial
This is an interventional screening trial for Carotid Atherosclerosis focused on measuring Complicated carotid atherosclerotic plaques, Endarterectomy, 99mTc-ANNexin-V-128
Eligibility Criteria
Inclusion Criteria:
- 18 years ≤ Age ≤ 90 years
- Patients with clinical indications to carotid endarterectomy
- Signed the consent form.
- Affiliation of a social security regime
Exclusion Criteria:
- Non-menopausal women
- Chronic kidney disease (eGFR < 45 ml/min/1.73 m2)
- Waldenstrom disease
- Multiple myeloma
- Previous severe adverse reaction to iodinated contrast agent
- Impossibility to stay immobile and maintain the supine position during 20 minutes.
- Altered consciousness or inability to understand the consent form.
- Urinary incontinence without implantation of urinary catheter (risk of urinary contamination).
- Non-atherosclerotic carotid stenosis (history of cervical radiation).
- Patient deprived of liberty or under legal protection measure
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
99mTc-Annexin-V-128 uptake on scintigraphy
Arm Description
Outcomes
Primary Outcome Measures
assess the concordance between the detection of 99mTc-Annexin-V-128 uptake on scintigraphy in carotid plaques with SPECT and the presence of complicated plaques on histology obtained after carotid endarterectomy
Concordance will be assessed by Cohen's kappa coefficient between:
- detection of 99mTc-Annexin-V-128 uptake on scintigraphy in the carotid bulb localized using the CTA 90 minutes after injection of the radiotracer ipsi-lateral to the carotid endarterectomy.
And
- presence of complicated atherosclerotic plaques after carotid endarterectomy validated by an Endpoint Adjudication Committee composed of vascular surgeons and pathologists that will review macroscopical aspects of carotid specimen and histology of all explanted carotid plaques.
Secondary Outcome Measures
to evaluate the correlation between the intensity of 99mTc-Annexin-V-128 uptake detected on SPECT and the expression of Annexin-V on immuno-histology of carotid plaques
Correlation: maximal Annexin-V-positive area will be quantified on serial sections of carotid plaques on immunohistochemistry.
to evaluate the relationship between the intensity of 99mTc-Annexin-V-128 uptake detected on SPECT and the morphological aspects of plaques on histology
morphological features of complicated atherosclerotic plaques (thrombus, lipid core, intra-plaque hemorrhage, plaque rupture) detected on histology.
to assess diagnostic performance of 99mTc-Annexin-V-128 scintigraphy for the detection of complicated carotid plaques detected on histology in patients referred for carotid endarterectomy.
Sensitivity and specificity estimation Complicated plaques will be defined as the presence of luminal or intra-plaque thrombus or the presence of plaque rupture detected on the carotid endarterectomy specimen with histology.
to compare the intensity of the 99mTc-Annexin-V-128 uptake in ipsilateral (symptomatic) and contralateral (asymptomatic) carotid artery.
maximal intensity of 99mTc-Annexin-V-128 uptake on scintigraphy in the carotid bulb localized using the CTA 90 minutes after injection of the radiotracer contralateral to carotid endarterectomy.
to test the intra- and inter-operator reproducibility of the analysis of 99mTc-Annexin-V-128 uptake in carotid bulb
Intra class correlation coefficients between operator measurement as Research methodology
Full Information
NCT ID
NCT03630835
First Posted
August 10, 2018
Last Updated
October 15, 2021
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT03630835
Brief Title
99m Tc-ANNexin-V-128 Scintigraphy for the Identification of Complicated Carotid Atherosclerotic Plaques
Acronym
ANNICA
Official Title
99m Tc-ANNexin-V-128 Scintigraphy for the Identification of Complicated Carotid Atherosclerotic Plaques
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Problem of supply of the experimental product (radio tracer).
Study Start Date
September 2018 (Anticipated)
Primary Completion Date
April 2020 (Anticipated)
Study Completion Date
April 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The aim of this trial will be to test and validate the value of scintigraphy with injection of 99mTc-Annexin-V-128 for the detection of complicated carotid plaques
Detailed Description
Introduction Stroke represents the third cause of death, the first cause of handicap and the second cause of dementia in Europe. Carotid atherosclerotic plaques are the cause of ischemic stroke in about 15 to 20 % of the patients. In presence of carotid stenosis > 50 %, the risk of ischemic stroke is estimated at about 10% per year when the patient has presented symptoms of cerebral ischemia but only at 2% per year in asymptomatic patients. Clinical benefits of surgical carotid endarterectomy have been demonstrated in symptomatic patients with high degree of carotid stenosis, but remain debatable in asymptomatic patients and should be balanced with the risks associated with the revascularization procedure. There is an urgent need to develop imaging tools that improve the identification of patients at highest risk of developing an ischemic stroke Cellular apoptosis is a key feature of ruptured plaques. Apoptotic macrophages release large amounts of tissue factor within the plaque thereby fostering thrombus formation when plaques rupture. Annexin-V is a 36-kDa protein that binds with high affinity and high specificity to phosphatidylserine (PS) head groups expressed on the cell surface at early stages of the apoptotic process. In addition, activated platelets express large amounts of PS at their surface. In a proof-of-concept study, 99mTc-Annexin-V uptake was detected by scintigraphy in carotid atherosclerotic plaques of 4 patients who presented an acute ischemic stroke and was associated with the presence of apoptotic cells on corresponding carotid plaques obtained after carotid endarterectomy procedure.
Design : Monocentric interventional non comparative study Investigational medicinal product(s): 99mTc-Annexin-V-128 Statistical procedure : Statistical analysis will be performed at the end of the study after blinded review and data freezing.
99mTc-Annexin-V-128 uptake will be analyzed as a binary variable considering the presence or absence of detection and as a quantitative variable for the intensity of signal.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carotid Atherosclerosis, Atherosclerotic Plaque
Keywords
Complicated carotid atherosclerotic plaques, Endarterectomy, 99mTc-ANNexin-V-128
7. Study Design
Primary Purpose
Screening
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
99mTc-Annexin-V-128 uptake on scintigraphy
Arm Type
Experimental
Intervention Type
Other
Intervention Name(s)
99mTc-Annexin-V-128 uptake on scintigraphy
Intervention Description
An intravenous catheter will be placed in the forearm and a dose of 370 Mega-Becquerels of 99mTc-Annexin-V-128 (1-2 ml) over 10 seconds will be injected through the catheter. The patient will wait for 90 minutes in semi-supine position for the clearance of the radiotracer from blood. At 90 minutes p.i., the patient will be placed in a supine position on the bed of a SPECT-CT gamma-camera. A SPECT acquisition including the heart and the brain will be performed over 20 minutes. At the end of the SPECT acquisition, the bed will move to the CT of the imaging system. A CT angiography will be acquired during the intravenous injection of 30-40 ml of iodinated CT contrast agent from the heart to the brain to localize the signal on the SPECT images. The iodinated contrast agent that is currently available at Bichat Hospital for CTA is Iomeron 400 provided by Bracco Imaging.
The total duration of the imaging study will be 2 hours.
Primary Outcome Measure Information:
Title
assess the concordance between the detection of 99mTc-Annexin-V-128 uptake on scintigraphy in carotid plaques with SPECT and the presence of complicated plaques on histology obtained after carotid endarterectomy
Description
Concordance will be assessed by Cohen's kappa coefficient between:
- detection of 99mTc-Annexin-V-128 uptake on scintigraphy in the carotid bulb localized using the CTA 90 minutes after injection of the radiotracer ipsi-lateral to the carotid endarterectomy.
And
- presence of complicated atherosclerotic plaques after carotid endarterectomy validated by an Endpoint Adjudication Committee composed of vascular surgeons and pathologists that will review macroscopical aspects of carotid specimen and histology of all explanted carotid plaques.
Time Frame
no later than one month after baseline.
Secondary Outcome Measure Information:
Title
to evaluate the correlation between the intensity of 99mTc-Annexin-V-128 uptake detected on SPECT and the expression of Annexin-V on immuno-histology of carotid plaques
Description
Correlation: maximal Annexin-V-positive area will be quantified on serial sections of carotid plaques on immunohistochemistry.
Time Frame
no later than one month after baseline.
Title
to evaluate the relationship between the intensity of 99mTc-Annexin-V-128 uptake detected on SPECT and the morphological aspects of plaques on histology
Description
morphological features of complicated atherosclerotic plaques (thrombus, lipid core, intra-plaque hemorrhage, plaque rupture) detected on histology.
Time Frame
no later than one month after baseline.
Title
to assess diagnostic performance of 99mTc-Annexin-V-128 scintigraphy for the detection of complicated carotid plaques detected on histology in patients referred for carotid endarterectomy.
Description
Sensitivity and specificity estimation Complicated plaques will be defined as the presence of luminal or intra-plaque thrombus or the presence of plaque rupture detected on the carotid endarterectomy specimen with histology.
Time Frame
no later than one month after baseline.
Title
to compare the intensity of the 99mTc-Annexin-V-128 uptake in ipsilateral (symptomatic) and contralateral (asymptomatic) carotid artery.
Description
maximal intensity of 99mTc-Annexin-V-128 uptake on scintigraphy in the carotid bulb localized using the CTA 90 minutes after injection of the radiotracer contralateral to carotid endarterectomy.
Time Frame
no later than one month after baseline.
Title
to test the intra- and inter-operator reproducibility of the analysis of 99mTc-Annexin-V-128 uptake in carotid bulb
Description
Intra class correlation coefficients between operator measurement as Research methodology
Time Frame
no later than one month after baseline.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18 years ≤ Age ≤ 90 years
Patients with clinical indications to carotid endarterectomy
Signed the consent form.
Affiliation of a social security regime
Exclusion Criteria:
Non-menopausal women
Chronic kidney disease (eGFR < 45 ml/min/1.73 m2)
Waldenstrom disease
Multiple myeloma
Previous severe adverse reaction to iodinated contrast agent
Impossibility to stay immobile and maintain the supine position during 20 minutes.
Altered consciousness or inability to understand the consent form.
Urinary incontinence without implantation of urinary catheter (risk of urinary contamination).
Non-atherosclerotic carotid stenosis (history of cervical radiation).
Patient deprived of liberty or under legal protection measure
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pierre AMARENCO, MD PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
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99m Tc-ANNexin-V-128 Scintigraphy for the Identification of Complicated Carotid Atherosclerotic Plaques
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