Carotid Artery DiseasesCADASNCT03721523
Carotid Artery Disease After Stroke (CADAS).
An observational study of Carotid Artery Diseases and Stroke, run by University of Manchester at 3 sites in United Kingdom.
Trial summary
Stroke is a significant medical problem with 150,000 events occurring per year in the UK and incurring healthcare costs of £4 billion per year. Fifty percent of strokes will leave a lasting disability on first manifestation and 10-15% (roughly 16,500 per year) are unheralded ischaemic events in previously asymptomatic… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Carotid Artery Diseases, Stroke, Transient Ischemic Attack
- What is being tested?
- 3 Dimensional tomographic Ultrasound and Platelet Aggregometry
- How many people
- 0 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Nov 2018to 9 Sep 2021
- Phase
- Observational
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with recent stroke, with carotid artery disease not being considered for surgery.
Who may be able to join
- Patients with capacity to give informed consent. All patients who have suffered a Partial Anterior Circulatory Stroke (PACS) or Transient Ischaemic Attack (TIA).
- Carotid Stenosis >50%.
Who cannot join
- Lacking capacity. Carotid Artery occlusion. Allergy to contrast agent. Significant disability or immobility such that participation would cause stress.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Manchester University hospitals NHS Foundation Trust
Manchester, Greater Manchester, M23 9LT
Northern Care Alliance, Salford Royal NHS Foundation Trust
Manchester, Greater Manchester
Manchester Foundation Trust, Wythenshawe site.
Manchester
About this study
Official title: Observational Cohort Study of Changes in Carotid Plaque Volume After Stroke.
Stroke is a significant medical problem with 150,000 events occurring per year in the UK and incurring healthcare costs of £4 billion per year. Fifty percent of strokes will leave a lasting disability on first manifestation and 10-15% (roughly 16,500 per year) are unheralded ischaemic events in previously asymptomatic Carotid artery disease.
Carotid Artery Disease is caused by the formation of an atherosclerotic plaque in the vessel. Stroke or TIA occurs when plaque or adherent thrombus breaks off and embolises to the brain, blocking off its blood supply. Hence, a carotid plaque is said to be symptomatic if it has caused a Stroke or TIA in the territory of the brain supplied by that vessel in the previous six months.
Read more
Currently, the degree of stenosis (narrowing) of the artery by doppler ultrasound is the main assessment performed. Doppler ultrasound measures stenosis and elevation of blood flow velocity in the artery prior to surgical intervention. However, it has been shown that the degree of stenosis is a poor predictor of stroke as many asymptomatic patients have severe stenosis and many symptomatic patients have moderate stenosis. Stenosis is a two dimensional assessment of a 3-D structure.
Other features of the plaque should be considered including the volume of the carotid plaque and its constituents. Carotid Plaque Volume has been measured in 339 individuals, with plaque volume being higher in symptomatic than asymptomatic individuals. In this study, plaque volume did not correlate with stenosis degree. No studies have been conducted measuring the change in carotid plaque volume and morphology following a stroke. This pilot study will perform serial duplex scans on recently symptomatic individuals over a 12 week period and observe the changes in Plaque Volume and morphology. This will attempt to prove that carotid plaque volume is a better predictor of stroke than stenosis. The investigators will also aim to identify other plaque features that may have an important role in predicting stroke risk. Documenting the timescale of change in plaque volume will aid us in defining appropriate timescales for treating the symptomatic population and when those having medical management's risk has returned to baseline. Observing the change in plaque immediately after stroke will improve our knowledge of the changes in plaques that lead to symptoms and may in the future help us predict which patients with asymptomatic carotid stenosis need operation.
Read the detailed description
Carotid Stenosis and stroke risk
Although carotid stenosis is the primary factor used to determine stroke risk and clinical priority in carotid artery disease, stenosis is in fact a poor predictor of stroke risk. Specifically, in asymptomatic patients with >70% carotid stenosis, the risk of ipsilateral stroke is under 2% a year. Therefore in these patients the benefit of intervention with carotid endarterectomy is minimal, in simple terms around 32 CEA's would need to be undertaken to prevent just one stroke in carotid artery disease patients over a five year follow up period. This clearly indicates that carotid stenosis itself is a poor indictor of stroke risk.
Several other factors have been proposed as potentially relevant to stroke risk determination in carotid artery disease.
Carotid plaque volume
Carotid plaque volume (CPV) is the actual volume of atherosclerotic plaque present within the carotid artery. CPV may impact on stroke risk in Carotid artery disease as an increased atherosclerotic burden may disrupt carotid flow leading to thrombus formation and subsequent embolisation leading to CVA.
A recent pilot study recruiting over 200 patients demonstrated that CPV in patients undergoing CEA within four weeks of symptoms was almost double of that seen in asymptomatic patients, with mean CPV in the symptomatic group being 1.1cm3 compared with 0.68cm3 in the asymptomatic group (p<0.001). Interestingly, carotid plaque volume was also shown to fall rapidly following symptoms of cerebral ischemia from 1.1cm3 within four weeks of cerebral symptoms to 0.91cm3 at six weeks and a mean of only 0.62 cm3 more than eight weeks following symptoms. This data demonstrated that there may be a crucial link between CPV and cerebrovascular symptoms in carotid artery disease and therefore between CPV and stroke risk in the disease.
Carotid Plaque Morphology
Various studies have detailed carotid plaque histology to identify features that are related to cerebrovascular symptoms. The main features being; intra-plaque haemorrhage, plaque ulceration, fibrous cap thickness and lipid rich necrotic core. Fisher et al showed plaque ulceration was significantly more common in plaques in symptomatic patients. Xu et al also reported that disruption of the luminal surface, by fibrous cap rupture, intraplaque haemorrhage or ulceration is indicative of a high risk lesion. The project aims to identify these features on 3D duplex.
3D Duplex
3D duplex has been used to measure plaque volume and is proven to be reliable. The inter and intra observer variability have been shown to be low but increase with reducing amounts of total plaque volume. The study hypothesises that Carotid Plaque volume will correlate more with risk of stroke than the degree of stenosis.
Antiplatelet Resistance
All carotid patients are treated with antiplatelet agents, commonly aspirin or clopidogrel, to reduce the incidence of thrombus formation around plaques. This intervention is thought to reduce stroke risk by around 9% annually and is therefore a key therapy in the management of carotid artery disease. Research has suggested that up to 37% of the population may be resistant to the actions of antiplatelet agents; if this is true in carotid artery disease patients it would represent a severe shortfall in current treatment and the prevalence and impact of this resistance may also impact on the risk of stroke in CAD patients. Patients will be tested for antiplatelet resistance at two timepoints to establish if they have resistance to the agents but also to see the effect of the acute embolic event on the efficacy of antiplatelet agents.
A recent pilot study involving 35 patients demonstrated a significant prevalence of antiplatelet resistance in CAD patients and showed an association between cerebrovascular symptoms and residual platelet aggregation. This further strengthens the hypothesis that antiplatelet resistance may be associated with stroke risk in CAD. Data from this project demonstrates that antiplatelet resistance may be prevalent in the CAD patient population and that the impact of this resistance, although potentially significant, is as yet not fully understood.
Schedule of events
The procedures will be performed at the following time intervals;
- < 7 days 3D Duplex + Platelet aggregometry
- Day 14 (+/- 2 days) 3D Duplex
- Day 28 (+/- 2 days) 3D Duplex
- Day 56 (+/- 2 days) 3D Duplex
- Day 84 (+/- 2 days) 3D Duplex + Platelet aggregometry
- Conditions
- Carotid Artery Diseases, Stroke, Transient Ischemic Attack
- Being tested
- 3 Dimensional tomographic Ultrasound, Platelet Aggregometry
- Medical subject headings
- Carotid Artery Diseases, Stroke, Ischemic Attack, Transient
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3 Dimensional tomographic UltrasoundDiagnostic test
3-D tUS at five timepoints following acute ipsilateral stroke or Transient Ischaemic attack (TIA) to document carotid plaque volume and presence or absence of adverse plaque features.
Platelet AggregometryDiagnostic test
Blood test to test for platelet resistance to aspirin or clopidogrel and to measure effect of acute inflammatory response post event.
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Carotid Plaque Volume using 3-D tomographic Ultrasound over time following acute cerebral event.
Measured by 3-D tUS with contrast administration
Measured: Measured at 5 separate timepoints up to 12 weeks following acute cerebral event.
Secondary outcomes (2)
Identify adverse morphological features within the carotid plaque by 3-D tomographic Ultrasound.
Duplex ultrasound to identify intraplaque haemorrhage, fibrous cap thickness, ulceration, juxtaluminal black area.
Measured: At five timepoints over 12 weeks.
Assess the acute inflammatory response to stroke on platelet aggregation and resistance to antiplatelet agents.
Platelet aggregometry blood test.
Measured: Twice during study period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2018
- Study startNov 2018 (estimated)
- Primary completion9 Sep 2021
- Study completion9 Sep 2021
Why it stopped: Unable to achieve recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carotid Artery DiseasesStudies of the same condition, open and under way.
- More trials run by University of ManchesterThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Manchester
- Sponsor type
- University, hospital or other
- Collaborators
- Manchester University NHS Foundation Trust
- Responsible party
- Principal investigator, Alison Phair, University of Manchester
- Investigators
- Charles McCollum, Prof., Principal investigator, University of Manchester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03721523
- Sponsor's protocol ID
- UHSMCADAS
- Acronym
- CADAS
- Status last verified
- Sep 2021
- First submitted
- 25 Oct 2018
- Last updated
- 27 Sep 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 27 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observational Cohort Study of Changes in Carotid Plaque Volume After Stroke.
- ClinicalTrials.gov ID
- NCT03721523
- Acronym / sponsor ID
- CADAS / UHSMCADAS
- Conditions
- Carotid Artery Diseases, Stroke, Transient Ischemic Attack
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Unable to achieve recruitment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of ManchesterUniversity, hospital or other
- Collaborators
- Manchester University NHS Foundation Trust
- Study start
- Nov 2018 (estimated)
- Primary completion
- 9 Sep 2021 (actual)
- Study completion
- 9 Sep 2021 (actual)
- First posted
- 26 Oct 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.
Stroke is a significant medical problem with 150,000 events occurring per year in the UK and incurring healthcare costs of £4 billion per year. Fifty percent of strokes will leave a lasting disability on first manifestation and 10-15% (roughly 16,500 per year) are unheralded ischaemic events in previously asymptomatic Carotid artery disease.
Carotid Artery Disease is caused by the formation of an atherosclerotic plaque in the vessel. Stroke or TIA occurs when plaque or adherent thrombus breaks off and embolises to the brain, blocking off its blood supply. Hence, a carotid plaque is said to be symptomatic if it has caused a Stroke or TIA in the territory of the brain supplied by that vessel in the previous six months.
Currently, the degree of stenosis (narrowing) of the artery by doppler ultrasound is the main assessment performed. Doppler ultrasound measures stenosis and elevation of blood flow velocity in the artery prior to surgical intervention. However, it has been shown that the degree of stenosis is a poor predictor of stroke as many asymptomatic patients have severe stenosis and many symptomatic patients have moderate stenosis. Stenosis is a two dimensional assessment of a 3-D structure.
Other features of the plaque should be considered including the volume of the carotid plaque and its constituents. Carotid Plaque Volume has been measured in 339 individuals, with plaque volume being higher in symptomatic than asymptomatic individuals. In this study, plaque volume did not correlate with stenosis degree. No studies have been conducted measuring the change in carotid plaque volume and morphology following a stroke. This pilot study will perform serial duplex scans on recently symptomatic individuals over a 12 week period and observe the changes in Plaque Volume and morphology. This will attempt to prove that carotid plaque volume is a better predictor of stroke than stenosis. The investigators will also aim to identify other plaque features that may have an important role in predicting stroke risk. Documenting the timescale of change in plaque volume will aid us in defining appropriate timescales for treating the symptomatic population and when those having medical management's risk has returned to baseline. Observing the change in plaque immediately after stroke will improve our knowledge of the changes in plaques that lead to symptoms and may in the future help us predict which patients with asymptomatic carotid stenosis need operation.
Detailed description
Carotid Stenosis and stroke risk
Although carotid stenosis is the primary factor used to determine stroke risk and clinical priority in carotid artery disease, stenosis is in fact a poor predictor of stroke risk. Specifically, in asymptomatic patients with >70% carotid stenosis, the risk of ipsilateral stroke is under 2% a year. Therefore in these patients the benefit of intervention with carotid endarterectomy is minimal, in simple terms around 32 CEA's would need to be undertaken to prevent just one stroke in carotid artery disease patients over a five year follow up period. This clearly indicates that carotid stenosis itself is a poor indictor of stroke risk.
Several other factors have been proposed as potentially relevant to stroke risk determination in carotid artery disease.
Carotid plaque volume
Carotid plaque volume (CPV) is the actual volume of atherosclerotic plaque present within the carotid artery. CPV may impact on stroke risk in Carotid artery disease as an increased atherosclerotic burden may disrupt carotid flow leading to thrombus formation and subsequent embolisation leading to CVA.
A recent pilot study recruiting over 200 patients demonstrated that CPV in patients undergoing CEA within four weeks of symptoms was almost double of that seen in asymptomatic patients, with mean CPV in the symptomatic group being 1.1cm3 compared with 0.68cm3 in the asymptomatic group (p<0.001). Interestingly, carotid plaque volume was also shown to fall rapidly following symptoms of cerebral ischemia from 1.1cm3 within four weeks of cerebral symptoms to 0.91cm3 at six weeks and a mean of only 0.62 cm3 more than eight weeks following symptoms. This data demonstrated that there may be a crucial link between CPV and cerebrovascular symptoms in carotid artery disease and therefore between CPV and stroke risk in the disease.
Carotid Plaque Morphology
Various studies have detailed carotid plaque histology to identify features that are related to cerebrovascular symptoms. The main features being; intra-plaque haemorrhage, plaque ulceration, fibrous cap thickness and lipid rich necrotic core. Fisher et al showed plaque ulceration was significantly more common in plaques in symptomatic patients. Xu et al also reported that disruption of the luminal surface, by fibrous cap rupture, intraplaque haemorrhage or ulceration is indicative of a high risk lesion. The project aims to identify these features on 3D duplex.
3D Duplex
3D duplex has been used to measure plaque volume and is proven to be reliable. The inter and intra observer variability have been shown to be low but increase with reducing amounts of total plaque volume. The study hypothesises that Carotid Plaque volume will correlate more with risk of stroke than the degree of stenosis.
Antiplatelet Resistance
All carotid patients are treated with antiplatelet agents, commonly aspirin or clopidogrel, to reduce the incidence of thrombus formation around plaques. This intervention is thought to reduce stroke risk by around 9% annually and is therefore a key therapy in the management of carotid artery disease. Research has suggested that up to 37% of the population may be resistant to the actions of antiplatelet agents; if this is true in carotid artery disease patients it would represent a severe shortfall in current treatment and the prevalence and impact of this resistance may also impact on the risk of stroke in CAD patients. Patients will be tested for antiplatelet resistance at two timepoints to establish if they have resistance to the agents but also to see the effect of the acute embolic event on the efficacy of antiplatelet agents.
A recent pilot study involving 35 patients demonstrated a significant prevalence of antiplatelet resistance in CAD patients and showed an association between cerebrovascular symptoms and residual platelet aggregation. This further strengthens the hypothesis that antiplatelet resistance may be associated with stroke risk in CAD. Data from this project demonstrates that antiplatelet resistance may be prevalent in the CAD patient population and that the impact of this resistance, although potentially significant, is as yet not fully understood.
Schedule of events
The procedures will be performed at the following time intervals;
- < 7 days 3D Duplex + Platelet aggregometry
- Day 14 (+/- 2 days) 3D Duplex
- Day 28 (+/- 2 days) 3D Duplex
- Day 56 (+/- 2 days) 3D Duplex
- Day 84 (+/- 2 days) 3D Duplex + Platelet aggregometry
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with recent stroke, with carotid artery disease not being considered for surgery.
Key inclusion criteria (2 listed)
- Patients with capacity to give informed consent. All patients who have suffered a Partial Anterior Circulatory Stroke (PACS) or Transient Ischaemic Attack (TIA).
- Carotid Stenosis >50%.
Key exclusion criteria (1 listed)
- Lacking capacity. Carotid Artery occlusion. Allergy to contrast agent. Significant disability or immobility such that participation would cause stress.
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 |
|---|---|---|
| 3 Dimensional tomographic Ultrasound3-D tUS at five timepoints following acute ipsilateral stroke or Transient Ischaemic attack (TIA) to document carotid plaque volume and presence or absence of adverse plaque features. | Diagnostic test | – |
| Platelet AggregometryBlood test to test for platelet resistance to aspirin or clopidogrel and to measure effect of acute inflammatory response post event. | Diagnostic test | – |
Primary outcome
Changes in Carotid Plaque Volume using 3-D tomographic Ultrasound over time following acute cerebral event.
Time frame: Measured at 5 separate timepoints up to 12 weeks following acute cerebral event.
Measured by 3-D tUS with contrast administration
2 secondary outcomes
Identify adverse morphological features within the carotid plaque by 3-D tomographic Ultrasound.
Time frame: At five timepoints over 12 weeks.
Assess the acute inflammatory response to stroke on platelet aggregation and resistance to antiplatelet agents.
Time frame: Twice during study period
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 27 Sep 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.
Charles McCollum, Prof. principal investigator
University of Manchester
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Carotid Artery Diseases and Stroke, run by University of Manchester at 3 sites in United Kingdom.
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 2 inclusion and 1 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 27 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
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?
Changes in Carotid Plaque Volume using 3-D tomographic Ultrasound over time following acute cerebral event. (time frame: Measured at 5 separate timepoints up to 12 weeks following acute cerebral event.). 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 27 Sep 2021; AzTrials last refreshed its copy on 3 Nov 2026.