Stratification of Patient With Carotid Disease
Stratification of Patient With Carotid Disease
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.
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.
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