MicroNet-covered Stent System for Stroke Prevention in All Comer Carotid Revascularization (PARADIGM-EXT)

Long-term Outcomes of MicroNet-covered Stent Routine Use for Stroke Prevention in Symptomatic and Increased-risk Asymptomatic Carotid Stenosis Patients Requiring Revascularization by Neurovascular Team Decision: PARADIGM-EXTEND

All-comer study of unselected patients suitable for carotid artery revascularization to evaluate the feasibility, efficacy and safety of first line endovascular revasculariztion using MicroNet covered stent (CGuard™) in the treatment of consecutive symptomatic and increased-stroke-risk asymptomatic carotid lesions that require revascularization by Neurovascular Team decision.

Study Overview

• Status: Recruiting
• Conditions: Carotid Artery Diseases
• Intervention / Treatment: Device: Carotid Artery Stenting

Detailed Description

Independent investigator initiated, academic, single arm, open-label, non-randomized, prospective, multicenter, multispecialty trial of CGuard™ routine use in all-comer population of consecutive patients with symptomatic or increased-stroke-risk asymptomatic carotid stenosis.

Increased-stroke-risk is defined as the following patient and/or lesion characteristics:

thrombus containing, documented progressive, irregular, ulcerated lesion; evidence of ipsilateral ischemic cerebral injury in MRI or CT imaging; contralateral stroke in relation to carotid stenosis; contralateral artery occlusion.

The main objective of this observational study is to evaluate (1) the periprocedural feasibility and efficacy of CGuard™ stent system in the treatment of carotid artery stenosis (2) long-term efficacy and safety of routine CGuard™ stent system use.

The study hypothesis is that the novel CGuard™ MicroNet® covered stent is safe and effective for a majority of consecutive patients considered to require carotid revascularization.

The multicenter arm of the project has a specific cohort descriptor: PARADIGM-EXTEND MC

• Study Type: Interventional
• Enrollment (Anticipated): 550
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Piotr Musialek, MD, PhD; Phone Number: +48126142287; Email: p.musialek@szpitaljp2.krakow.pl

Study Locations

• Poland
  • Maloplska
    • Kraków, Maloplska, Poland, 31-202
      • Recruiting
      • Department of Cardiac and Vascular Diseases, The John Paul II Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

General Inclusion Criteria:

• Patient > 18 years old qualified by NeuroVascular Team for carotid revascularization according to local standards of care
• Signed informed consent
• Agreement (routin un this group of patients) to clinical and ultrasonographis follow up.

Angiographic Inclusion Criteria:

• De-novo atherosclerotic lesions or neo-atherosclerosis
• Symptomatic patients (history of transient ischemic attack, ischaemic stroke or amaurosis fugax within 6 months from index procedure) with index artery stenosis ≥50% assessed in angiography with NASCET method or
• Asymptomatic patients with index artery stenosis ≥70-80% assessed in angiography with NASCET method

General Exclusion Criteria:

• Lack of NeuroVascular Team agreement on carotid revascularization indication
• Lack of signed informed consent
• Estimated life expectancy less than 1 year
• Chronic renal failure with serum creatinine level > 3.0 mg/dL
• Myocardial Infarction within 72 hours prior to index procedure.
• Pregnant women
• Diagnosed coagulopathies
• History of contrast media allergy, not reacting to pharmacotherapy

Angiographic Exclusion Criteria:

• Index lesion occlusion
• Common carotid artery stent protruding to aortic arch
• Anatomical conditions restricting stent implantation
• Significant common carotid artery stenosis proximal to index lesion (unless treated)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carotid Artery Stenting; Consecutive male and female patients older than 18 year with symptomatic and increased-stroke-risk asymptomatic carotid lesions that require revascularization by Neurovascular Team decision.	Device: Carotid Artery Stenting; Carotid artery stenting according to local clinical experience and ESC/ESVS guidelines using exclusively CGuard™, MicroNet covered stent under proximal or distal intraprocedural cerebral protection according to "tailored CAS" algorithm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MACNE (Major Adverse Cardiac and Neurological Events)	Death, Stroke, Myocardial Infarction.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procedural success	Successful stent delivery and deployment without complication	Within 48 hours from index procedure
In-hospital MACNE (Major Adverse Cardiac and Neurological Events)	Death, Stroke, Myocardial Infarction within index hospitalization	Within 48 hours from index procedure
30-day MACNE (Major Adverse Cardiac and Neurological Events)	Death, Stroke, Myocardial Infarction within 30 days	30 days
Incidence of any periprocedural complications	Any periprocedural complications	Within 48 hours
Functional MRI efficacy assessment.	In case of fMRI evaluation, pre and postprocedural imaging.	Within 48 hours
Diffusion Weighted MRI efficacy assessment.	In case of DW-MRI evaluation, new ischemic lesions according to protocol criteria in postprocedural imaging.	Within 48 hours
Intravascular Ultrasound Stent Evaluation	In case of IVUS examination, postprocedural stent expansion, apposition and carotid plaque sequestration evaluation.	Periprocedural
Ipsilateral Stroke incidence	Ischemic stoke at the site of index procedure.	From one month until one year after the procedure.
Ipsilateral Stroke incidence	Ischemic stoke at the site of index procedure.	From one year until five years after the procedure.
Any stroke incidence	Any stroke during study observational period.	Within five years from the procedure.
Peak Systolic Velocity in Duplex Ultrasound evaluation in target vessel	Peak-systolic and End-diastolic Velocities assessed with DUS peri-proceduraly.	Periprocedural
Peak Systolic Velocity in Duplex Ultrasound evaluation in target vessel	Peak-systolic and End-diastolic Velocities assessed with DUS 30 day after discharge.	Within 30 days after index procedure.
Peak Systolic Velocity in Duplex Ultrasound evaluation in target vessel	Peak-systolic and End-diastolic Velocities assessed with DUS one year after discharge.	One year after index procedure.

Collaborators and Investigators

• Sponsor: John Paul II Hospital, Krakow
• Collaborators: Jagiellonian University
• Investigators: Principal Investigator: Piotr Musialek, MD, PhD, Jagiellonian University

Publications and helpful links

General Publications

• Aboyans V, Ricco JB, Bartelink MEL, Bjorck M, Brodmann M, Cohnert T, Collet JP, Czerny M, De Carlo M, Debusa S, Espinola-Klein C, Kahan T, Kownator S, Mazzolai L, Naylora AR, Roffi M, Rotherb J, Sprynger M, Tendera M, Tepe G, Venermoa M, Vlachopoulos C, Desormais I. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS). Rev Esp Cardiol (Engl Ed). 2018 Feb;71(2):111. doi: 10.1016/j.rec.2017.12.014. No abstract available. English, Spanish.
• Brott TG, Howard G, Roubin GS, Meschia JF, Mackey A, Brooks W, Moore WS, Hill MD, Mantese VA, Clark WM, Timaran CH, Heck D, Leimgruber PP, Sheffet AJ, Howard VJ, Chaturvedi S, Lal BK, Voeks JH, Hobson RW 2nd; CREST Investigators. Long-Term Results of Stenting versus Endarterectomy for Carotid-Artery Stenosis. N Engl J Med. 2016 Mar 17;374(11):1021-31. doi: 10.1056/NEJMoa1505215. Epub 2016 Feb 18.
• Rosenfield K, Matsumura JS, Chaturvedi S, Riles T, Ansel GM, Metzger DC, Wechsler L, Jaff MR, Gray W; ACT I Investigators. Randomized Trial of Stent versus Surgery for Asymptomatic Carotid Stenosis. N Engl J Med. 2016 Mar 17;374(11):1011-20. doi: 10.1056/NEJMoa1515706. Epub 2016 Feb 17.
• Sardar P, Chatterjee S, Aronow HD, Kundu A, Ramchand P, Mukherjee D, Nairooz R, Gray WA, White CJ, Jaff MR, Rosenfield K, Giri J. Carotid Artery Stenting Versus Endarterectomy for Stroke Prevention: A Meta-Analysis of Clinical Trials. J Am Coll Cardiol. 2017 May 9;69(18):2266-2275. doi: 10.1016/j.jacc.2017.02.053.
• Janczak D, Malinowski M, Ziomek A, Kobecki J, Lesniak M, Dorobisz T, Dorobisz K, Janczak D, Chabowski M. Carotid artery stenting versus endarterectomy for the treatment of both symptomatic and asymptomatic patients with carotid artery stenosis: 2 years' experience in a high-volume center. Adv Clin Exp Med. 2018 Dec;27(12):1691-1695. doi: 10.17219/acem/75902.
• de Donato G, Setacci F, Sirignano P, Galzerano G, Cappelli A, Setacci C. Optical coherence tomography after carotid stenting: rate of stent malapposition, plaque prolapse and fibrous cap rupture according to stent design. Eur J Vasc Endovasc Surg. 2013 Jun;45(6):579-87. doi: 10.1016/j.ejvs.2013.03.005. Epub 2013 Apr 10.
• Kotsugi M, Takayama K, Myouchin K, Wada T, Nakagawa I, Nakagawa H, Taoka T, Kurokawa S, Nakase H, Kichikawa K. Carotid Artery Stenting: Investigation of Plaque Protrusion Incidence and Prognosis. JACC Cardiovasc Interv. 2017 Apr 24;10(8):824-831. doi: 10.1016/j.jcin.2017.01.029.
• Schofer J, Musialek P, Bijuklic K, Kolvenbach R, Trystula M, Siudak Z, Sievert H. A Prospective, Multicenter Study of a Novel Mesh-Covered Carotid Stent: The CGuard CARENET Trial (Carotid Embolic Protection Using MicroNet). JACC Cardiovasc Interv. 2015 Aug 17;8(9):1229-1234. doi: 10.1016/j.jcin.2015.04.016.
• Pieniazek P, Musialek P, Kablak-Ziembicka A, Tekieli L, Motyl R, Przewlocki T, Moczulski Z, Pasowicz M, Sokolowski A, Lesniak-Sobelga A, Zmudka K, Tracz W. Carotid artery stenting with patient- and lesion-tailored selection of the neuroprotection system and stent type: early and 5-year results from a prospective academic registry of 535 consecutive procedures (TARGET-CAS). J Endovasc Ther. 2008 Jun;15(3):249-62. doi: 10.1583/07-2264.1.
• Musialek P, Grunwald IQ. How asymptomatic is "asymptomatic" carotid stenosis? Resolving fundamental confusion(s) - and confusions yet to be resolved. Pol Arch Intern Med. 2017 Nov 30;127(11):718-719. doi: 10.20452/pamw.4157. Epub 2017 Nov 30. No abstract available.
• Musialek P, Hopf-Jensen S. Commentary: Carotid Artery Revascularization for Stroke Prevention: A New Era. J Endovasc Ther. 2017 Feb;24(1):138-148. doi: 10.1177/1526602816671263. Epub 2016 Oct 13. No abstract available.
• Musialek P, Hopkins LN, Siddiqui AH. One swallow does not a summer make but many swallows do: accumulating clinical evidence for nearly-eliminated peri-procedural and 30-day complications with mesh-covered stents transforms the carotid revascularisation field. Postepy Kardiol Interwencyjnej. 2017;13(2):95-106. doi: 10.5114/pwki.2017.69012. Epub 2017 Jul 19.
• Stabile E, de Donato G, Musialek P, De Loose K, Nerla R, Sirignano P, Chianese S, Mazurek A, Tesorio T, Bosiers M, Setacci C, Speziale F, Micari A, Esposito G. Use of Dual-Layered Stents in Endovascular Treatment of Extracranial Stenosis of the Internal Carotid Artery: Results of a Patient-Based Meta-Analysis of 4 Clinical Studies. JACC Cardiovasc Interv. 2018 Dec 10;11(23):2405-2411. doi: 10.1016/j.jcin.2018.06.047.
• Musialek P. TASTE-less endpoint of 30-day mortality (and some other issues with TASTE) in evaluating the effectiveness of thrombus aspiration in STEMI: not the "evidence" to change the current practice of routine consideration of manual thrombus extraction. Kardiol Pol. 2014;72(6):479-87. doi: 10.5603/KP.a2014.0022. Epub 2014 Feb 14. No abstract available.
• Musialek P, Mazurek A, Trystula M, Borratynska A, Lesniak-Sobelga A, Urbanczyk M, Banys RP, Brzychczy A, Zajdel W, Partyka L, Zmudka K, Podolec P. Novel PARADIGM in carotid revascularisation: Prospective evaluation of All-comer peRcutaneous cArotiD revascularisation in symptomatic and Increased-risk asymptomatic carotid artery stenosis using CGuard MicroNet-covered embolic prevention stent system. EuroIntervention. 2016 Aug 5;12(5):e658-70. doi: 10.4244/EIJY16M05_02.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): June 1, 2026

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: February 13, 2020
• First Posted (Actual): February 17, 2020

Study Record Updates

• Last Update Posted (Actual): March 29, 2022
• Last Update Submitted That Met QC Criteria: March 14, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Stenting
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carotid Artery Diseases
• Other Study ID Numbers: PARADIGM-EXTEND

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No