Clinical trial NCT03495830: Stratification of Patient With Carotid Disease
Official title: Observational Multicentre Clinical Trial for Validation of Taxinomisis, New Stratification Tool for Stroke Risk in Patients With Carotid Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Carotid Artery Stenosis
Lead sponsor: University of Belgrade
Sponsor class: OTHER
Collaborators: name: Ludwig-Maximilians - University of Munich
name: University of Barcelona
name: University of Athens
name: University of Genova
name: Utrecht University
First posted: 2018-04-12
Enrollment: 270
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with extracranial carotid stenosis greater than 50% stenosis (NASCET) in the carotid bifurcation or internal carotid artery assessed by means of ultrasound

Brief summary: Introduction: Taxinomisis trial is part of the Taxinomisis project. The concept of the Taxinomisis project is to stratify carotid artery disease relying on new modern data corresponding to contemporary patients based on information from longitudinal studies. Taxinomisis trial will validate this tool and adjust such stratification. Initial step of the project is characterization of symptomatic and asymptomatic carotid atherosclerotic plaque lesions, identification of risk and susceptibility factors through the exploitation of longitudinal cohort data and multiomics and disintegration of carotid artery disease phenotypes into endotypes through joint modeling of multipleomics data sets and systems medicine approaches. Finally such stratification model will be validated and adjusted in the Taxinomisis clinical trial.

Detailed description: Aim of the trial is to validate TAXINOMISIS system for risk stratification of carotid artery stenotic disease. Primary endpoints are stroke, transitory ischemic attack or retinal symptom while secondary endpoints are MRI silent brain lesions and carotid plaque progression.

Patient with moderate to severe extra-cranial, both asymptomatic and symptomatic, carotid artery stenosis will be enrolled in the prospective observational multi-center trial in five European (Athens, Barcelona, Belgrade, Genoa, Munich and Utrecht) vascular centers. Inclusion will last from 31.3.2018 - 01.06.2019. Patients with short life expectancy, high potential of stroke from other cause or patients with complex and tandem carotid lesions will be excluded from the trial.

Included patients will be examined clinically, basic laboratory exam will be performed and part of blood specimen will be stored and assessed later. Carotid plaque will be analysed by means of duplex and MRI image while brain lesions will be detected on brain MRI.

Treatment strategy will be dependent on guidelines of good clinical practice and let independently to institutional multidisciplinary panelist board. In patients treated with carotid endarterectomy (CEA) carotid plaque will be stored and assessed for future analysis. In respect to allocated therapy patients will follow different follow up protocols.

Intervention group: Patients undergoing intervention CEA or carotid artery stenting (CAS), will be followed by clinical examination and carotid duplex on 12, 24 and 36 month. If there is coexisting contralateral carotid stenosis greater than 50% and not requiring interventional treatment (CEA or CAS), patient should cross in optimal medical therapy group.

Optimal medical therapy group: Patients not subjected to intervention (or in whom one carotid has been treated with CAS or CEA and contra-lateral stenosis is greater than 50%) will be followed with carotid duplex (at 12, 24 and 36 months) and MRI imaging of carotid tree from aortic arch up to the circle of Willis after 12 and 36 months.

Trial plans to recruit 270 patients distributed in participating centers based on individual capabilities of each center. The diagnostic performance of the new risk model, and its accuracy to discriminate high versus low risk cases for cerebrovascular complications from carotid artery disease will be evaluated using Receiver Operating Characteristic (ROC) curve analysis. The accuracy (discriminated ability) of the model will be assessed by measuring the Area under the ROC curve (AUC). An AUC 0.80 and 90% CI, for the sensitivity of prediction model of 80% with marginal error of 10%, will be targeted.

Trial will terminate after finalizing 36 months of follow up for included patients at June 2022.

Eligibility criteria: Inclusion Criteria:

* Extracranial carotid stenosis greater than 50% stenosis (NASCET) in the carotid bifurcation or internal carotid artery assessed by means of ultrasound;
* Ability of the patient for follow-up examinations;
* Personally signed informed consent

Exclusion Criteria:

* Previous haemorrhagic stroke,
* Non-atherosclerotic carotid stenosis (e.g. dissection, floating thrombus, fibromuscular dysplasia, postirradiation lesion)
* Presence of stenotic lesions in the proximal common carotid artery,
* Recurrent carotid stenosis after CEA or CAS,
* Carotid aneurysm
* Bilateral carotid occlusion,
* Severe aortic arch calcifications and shaggy aorta
* Intracranial angioma or aneurysms,
* Severe pre-existing disability (modified Rankin scale ≥ 3);
* Contraindications for heparin, ASA and clopidogrel therapy
* Contraindication for MRI examination (metal implants, claustrophobia);
* Increased risk of thrombotic or embolic events (congenital or acquired thrombotic conditions, active untreated cancer, atrial fibrillation, severe cardiomyopathy with ejection fraction lower than 30%);
* Planned major surgery and/or life expectancy less than 3 years

Primary outcomes:
measure: Combined stroke, transitory ischemic attach and retinal transitory ischemic attach
timeFrame: 3 years
Secondary outcomes:
measure: Silent brain lesions
timeFrame: 3 years
Other outcomes:
Locations:
city: Munich
country: Germany
facility: University of Munich
city: Utrecht
country: Netherlands
facility: University of Utrecht
city: Belgrade
country: Serbia
facility: Clinic for Vascular and Endovascular Surgery, Serbian Clinical Centre
city: Barcelona
country: Spain
facility: University of Barcelona
Study officials:
affiliation: University of Ionania
name: Dimitris Fotiadis, PhD
role: STUDY_DIRECTOR
References: