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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Withdrawn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
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

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

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

    First Posted
    August 10, 2018
    Last Updated
    October 15, 2021
    Sponsor
    Assistance Publique - Hôpitaux de Paris
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    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

    Learn more about this trial

    99m Tc-ANNexin-V-128 Scintigraphy for the Identification of Complicated Carotid Atherosclerotic Plaques

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