Plaque Prolapse Prevention Carotid Artery Stenting (3PCAS)
Condition: Cerebrovascular Disease
MeSH terms: Cerebrovascular Disorders; Prolapse
Study type: Interventional

Summary: 
      The aim of the present positive-control study is to analyze and compare the rate of off-table
      subclinical neurological events in two groups of patients submitted to carotid artery
      stenting (CAS) with two different kind of stents, a close-cell stent, and the new
      mesh-covered stent, so to verify if the new model of stent is effective in preventing
      postprocedural carotid plaque embolism.
    

Detailed description: 
      Scientific background and explanation of rationale: CAS in selected asymptomatic patients has
      proven to be effective in reducing the risk of carotid-related neurological ischemic events
      in selected patients. It also carries a not-negligible risk of intraprocedural and
      postprocedural (so-called "off-table") embolic events causing clinical (TIA, stroke, death)
      and subclinical (Magnetic Resonance Imaging - MRI-detectable microembolic brain lesions,
      cognitive impairment, increase in markers of brain injury) morbidity. CAS technique has
      progressively refined in order to minimize the risk of intraprocedural embolism, but despite
      the increasing use of close-cell design stents the risk of plaque prolapse through the stent
      struts and of postprocedural embolism still exists. In order to prevent plaque prolapse a new
      stent design has been conceived and realized. It combines the traditional open-cell design to
      an exterior PET mesh that is able to capture and keep in place plaque debris as small as
      150-180µm.

      The aim of the present positive-control study is to analyze and compare the rate of off-table
      subclinical neurological events in two groups of patients submitted to CAS with two different
      kind of stents, a close-cell stent, and the new mesh-covered stent, so to verify if the new
      model of stent is effective in preventing postprocedural carotid plaque embolism.

      Methods

      Trial Design: single-center, superiority, randomized controlled trial comparing results
      between two different carotid stents in patients affected by asymptomatic ≥70% carotid artery
      stenosis.

      Participants:

      CAS inclusion criteria are: age more than 55 years, presence of a carotid stenosis ≥70%
      (NASCET evaluation criteria), with no previous neurologic symptoms referred in the medical
      history, absence of a previous brain ischemic lesion detected at Diffusion Weighted (DW)-MRI.
      Patients with symptomatic carotid lesions, previous ischemic lesions detected at DW-MRI, or
      inability to give consent will be excluded from the study.

      Exclusion criteria for CAS are: significant contraindications to angiography, history of
      bleeding disorder, or intracranial aneurysm or vascular malformation or hemorrhage, presence
      of intraluminal thrombus, poor entry points at the femoral artery, type 2-3 arch, bovine
      arch, severe aortic arch or ipsilateral ostial common carotid or brachiocephalic
      atherosclerosis, severe proximal common or distal internal carotid artery tortuosity, sharply
      angulated internal carotid artery, carotid string sign, circumferential calcification of
      carotid plaque, length of the target lesion requiring more than one stent.

      Eligibility criteria for randomization are: obtained informed consent, compliance to the
      study protocol. Patients will be randomized to receive either carotid Wallstent (Boston
      Scientific, Marlborough, MA, USA) or C-Guard carotid stent (Inspire-MD, Tel-Aviv, Israel) a
      new mesh-covered open-cell stent.

      Written informed consent will be obtained before enrollment. Setting: data will be collected
      and analyzed at our Vascular Unit Academic Centre.

      Interventions: CAS interventions will be performed with distal embolic protection device in
      all cases (Filterwire, Boston Scientific, Marlborough, MA, USA) . Wallstent or C-Guard stent
      will be alternatively used to cover the whole plaque surface.

      DW-MRI performance: all patients will be submitted to preoperative, immediate postoperative,
      and 72 hours postoperatively DW-MRI. The comparison between immediate postoperative and
      72-hour examinations will detect any off-table events. Presence of recent ischemic lesions at
      preoperative examination will be considered an exclusion criterion for entering the study.

      MiniMentalStateExamination (MMSE) Test and MontrealCognitive Assessment (MOCA) Test
      administration and interpretation: all patients will be submitted to preoperative and 72-hour
      postoperative MMSE and MOCA tests in order to prove the effect of CAS-related microemboli on
      cognitive performance. The research assistant responsible for performing the tests
      preoperatively and postoperatively in all patients is trained to administer and score the
      tests. Downgrading in the postoperative examination, such as from normal to some cognitive
      impairment (1 step) or a difference ≥4 in the postoperative score compared with the
      preoperative value will be considered significant. No psychotropic or sedative medications
      will be administered to the patients before performing tests.

      NeuroSpecificEnolase (NSE) and S100β serum levels detection and analysis: The S100 test
      measures the β-subunit of protein S100 as defined by three monoclonal antibodies with a
      detection limit of 0.02 µg/L. NSE measurement is based on monoclonal antibodies that bind to
      the γ-subunit of the enzyme with a minimal measurable concentration of 0.3 µg/L. S100β and
      NSE proteins will be analyzed by the use of automated immunoluminometric assays (S100 Elecsys
      test, Roche Diagnostics GmbH, Mannheim, Germany; ELSA-NSE, CIS Bio International,
      Gif-sur-Yvette Cedex, France). Venous blood samples will be obtained for each patient
      preoperatively (basal sample), at 5 minutes after embolic protection device retrieval, and at
      2, 12, 24, and 48 hours after the end of the procedure. Samples will be allowed to clot.
      After centrifugation (1800g for 6 minutes) ≤20 minutes from collection, serum will be stored
      at -80°C for later analysis.

      Objective: to demonstrate a decrease in off-table microembolic event rate in patients
      submitted to CAS with C-Guard stent implantation compared to patients with Wallstent
      implantation, detected by DW-MRI, markers of brain injury, and neuropsychometric tests.

      Sample size estimation: assuming a type I error α=0.05, a type II error β=0.20, so a power
      (1-β)=0.80, an event rate in the control (Wallstent) group of 0.40 (40%), an event rate in
      the treatment (C-Guard) group of 0.10 (10%), so assuming a 30% event rate reduction in the
      treatment group, the estimation of sample size for each treatment group is 29.

      Randomisation: a computer-generated random allocation sequence would be used. A blocked
      randomization will be performed with an allocation ratio 1:1. Allocation concealment will be
      used. Blind postprocedural DW-MRI assessment/interpretation, neurobiomarkers levels
      evaluation, and MMSE and MOCA administration will be done by those assessing outcomes.
    

Intervention name(s): Carotid stenting procedure by carotid stent implantation
Intervention type(s): Procedure
Intervention description(s): Carotid stenting procedure by carotid stent implantation
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: carotid disease; stroke; stent; carotid stenting