Clinical trial NCT03630835: 99m Tc-ANNexin-V-128 Scintigraphy for the Identification of Complicated Carotid Atherosclerotic Plaques
Official title: 99m Tc-ANNexin-V-128 Scintigraphy for the Identification of Complicated Carotid Atherosclerotic Plaques
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: Carotid Atherosclerosis
Atherosclerotic Plaque
Keywords: Complicated carotid atherosclerotic plaques
Endarterectomy
99mTc-ANNexin-V-128
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2018-08-15
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

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.

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

Primary outcomes:
measure: 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
timeFrame: no later than one month after baseline.
Secondary outcomes:
measure: 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
timeFrame: no later than one month after baseline.
measure: to evaluate the relationship between the intensity of 99mTc-Annexin-V-128 uptake detected on SPECT and the morphological aspects of plaques on histology
timeFrame: no later than one month after baseline.
measure: 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.
timeFrame: no later than one month after baseline.
measure: to compare the intensity of the 99mTc-Annexin-V-128 uptake in ipsilateral (symptomatic) and contralateral (asymptomatic) carotid artery.
timeFrame: no later than one month after baseline.
measure: to test the intra- and inter-operator reproducibility of the analysis of 99mTc-Annexin-V-128 uptake in carotid bulb
timeFrame: no later than one month after baseline.
Other outcomes:
Locations:
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Pierre AMARENCO, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: