Carotid AtherosclerosisPhase 2/3ANNICANCT03630835
99m Tc-ANNexin-V-128 Scintigraphy for the Identification of Complicated Carotid Atherosclerotic Plaques
A Phase 2/3 study testing 99mTc-Annexin-V-128 uptake on scintigraphy in people with Carotid Atherosclerosis and Atherosclerotic Plaque, run by Assistance Publique - Hôpitaux de Paris.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Carotid Atherosclerosis, Atherosclerotic Plaque
- What is being tested?
- 99mTc-Annexin-V-128 uptake on scintigraphy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Sep 2018to Apr 2020
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years ≤ Age ≤ 90 years
- Patients with clinical indications to carotid endarterectomy
- Signed the consent form.
- Affiliation of a social security regime
Who cannot join
- 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.
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- 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
About this study
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
Read the 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.
- Conditions
- Carotid Atherosclerosis, Atherosclerotic Plaque
- Being tested
- 99mTc-Annexin-V-128 uptake on scintigraphy
- Keywords
- Complicated carotid atherosclerotic plaques, Endarterectomy, 99mTc-ANNexin-V-128
- Medical subject headings
- Carotid Artery Diseases, Plaque, Atherosclerotic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
99mTc-Annexin-V-128 uptake on scintigraphyOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 99mTc-Annexin-V-128 uptake on scintigraphy | Experimental | Not described Receives: Other: 99mTc-Annexin-V-128 uptake on scintigraphy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: no later than one month after baseline.
Secondary outcomes (5)
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.
Measured: no later than one month after baseline.
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.
Measured: no later than one month after baseline.
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.
Measured: no later than one month after baseline.
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.
Measured: no later than one month after baseline.
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
Measured: no later than one month after baseline.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2018
- Study startSep 2018 (estimated)
- Primary completionApr 2020 (estimated)
- Study completionApr 2020 (estimated)
Why it stopped: Problem of supply of the experimental product (radio tracer).
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carotid AtherosclerosisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pierre AMARENCO, MD PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03630835
- Sponsor's protocol ID
- P170602
- Other IDs
- 2017-002952-99, 2017
- Acronym
- ANNICA
- Status last verified
- Oct 2021
- First submitted
- 10 Aug 2018
- Last updated
- 20 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 99m Tc-ANNexin-V-128 Scintigraphy for the Identification of Complicated Carotid Atherosclerotic Plaques
- ClinicalTrials.gov ID
- NCT03630835
- Acronym / sponsor ID
- ANNICA / P170602
- Conditions
- Carotid Atherosclerosis, Atherosclerotic Plaque
- Keywords
- Complicated carotid atherosclerotic plaques, Endarterectomy, 99mTc-ANNexin-V-128
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Problem of supply of the experimental product (radio tracer).
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Sep 2018 (estimated)
- Primary completion
- Apr 2020 (estimated)
- Study completion
- Apr 2020 (estimated)
- First posted
- 15 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 99mTc-Annexin-V-128 uptake on scintigraphy | Experimental | Other: 99mTc-Annexin-V-128 uptake on scintigraphy |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 18 years ≤ Age ≤ 90 years
- Patients with clinical indications to carotid endarterectomy
- Signed the consent form.
- Affiliation of a social security regime
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 99mTc-Annexin-V-128 uptake on scintigraphyAn 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. | Other | 99mTc-Annexin-V-128 uptake on scintigraphy |
Primary outcome
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
Time frame: no later than one month after baseline.
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.
5 secondary outcomes
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
Time frame: no later than one month after baseline.
to evaluate the relationship between the intensity of 99mTc-Annexin-V-128 uptake detected on SPECT and the morphological aspects of plaques on histology
Time frame: no later than one month after baseline.
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.
Time frame: no later than one month after baseline.
to compare the intensity of the 99mTc-Annexin-V-128 uptake in ipsilateral (symptomatic) and contralateral (asymptomatic) carotid artery.
Time frame: no later than one month after baseline.
to test the intra- and inter-operator reproducibility of the analysis of 99mTc-Annexin-V-128 uptake in carotid bulb
Time frame: no later than one month after baseline.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pierre AMARENCO, MD PhD principal investigator
Assistance Publique - Hôpitaux de Paris
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing 99mTc-Annexin-V-128 uptake on scintigraphy in people with Carotid Atherosclerosis and Atherosclerotic Plaque, run by Assistance Publique - Hôpitaux de Paris.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 20 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: no later than one month after baseline.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2021.