Last updated on July 2019

CONFIDENCE Trial - Carotid Stent Trial to Evaluate the Safety and Efficacy of the Roadsaver™ Stent Used in Conjunction with the Nanoparasol® Embolic Protection System for Patients at Increased Risk for Adverse Events from Carotid Endarterectomy

Brief description of study

CONFIDENCE Trial - Carotid Stent Trial to Evaluate the Safety and Efficacy of the Roadsaver™ Stent Used in Conjunction with the Nanoparasol® Embolic Protection System for Patients at Increased Risk for Adverse Events from Carotid Endarterectomy

Detailed Study Description

Cardiovascular disease is the leading cause of morbidity and mortality in industrialized nations, and atherosclerosis has been linked as the chief underlying pathology.

Stroke as a result of the atherosclerotic carotid artery disease (CAD) is a common cause of death and a major reason for long-term disability worldwide1. Currently, it is estimated that stenosis of the internal carotid artery (ICA) may be responsible for up to 15-20% of all strokes or transient ischemic attacks (TIA)2. Additionally, patients with severe stenosis of these arteries present a greater risk for a subsequent stroke. Medical management using blood-thinning medications and control of blood pressure and cholesterol have limited benefits to reverse the stenosis and in preventing further disability. Alternatively, two treatment options for the revascularization of carotid artery stenosis have been advocated: (i) Carotid endarterectomy (CEA) surgery and (ii) an endovascular approach of carotid artery stenting (CAS).

Since the first carotid endarterectomies pioneered by DeBakey and Eastcott et al. in the 1950’s, the technique has evolved over the years and has become a standard for the treatment of atherosclerotic carotid artery disease3,4. The “Guidelines for Carotid Endarterectomy,” which appeared simultaneously in Stroke and Circulation in January 1995, have provided major contributions to the understanding of asymptomatic carotid disease derived from publication of the Asymptomatic Carotid Atherosclerosis Study (ACAS)5. In order to prevent stroke, carotid endarterectomy has been extensively used as a primary option to eliminate both hemodynamic stenosis and the source of cerebral atheroemboli improving blood flow. CEA has traditionally been the standard surgical treatment for severe carotid artery stenosis (=70%). The outcomes of surgery compared to medical therapy are well known as evidenced in findings from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST), wherein endarterectomy was shown to significantly reduce the risks of stroke in recent symptomatic patients with severe carotid stenosis6,7. However, general anesthesia employed in this surgery still carries the risk of stroke, myocardial infarction, and cranial or superficial nerve damage.

While the effectiveness of carotid endarterectomy in stenotic patients has been studied in well-designed trials8- 11, substantial limitations and risks continue to present challenges to the treating physician. There is a significant unmet need to increase procedural success, reduce the number of treatment steps, and prevent plaque prolapse and late event reduction.

Consequently, carotid artery stenting was first introduced as an endovascular therapy for carotid stenosis in the early 1990s with the development of first generation stents suitable for use in the carotid artery such as the Wallstent (Schneider, USA), Strecker (Medi-Tech, USA), and Palmaz Schatz (Johnson and Johnson, USA). The first generation stents evolved to provide a therapeutic option for high surgical risk patients for whom CEA was contraindicated, but with some unpleasant issues. These issues related to first generation stent systems in terms of stent compression and embolization of plaque debris to the brain were addressed with the advent of selfexpanding nickel-titanium (Nitinol) stents and embolic protection devices.

Carotid stenting, like CEA, carries a risk of stroke and therefore various trials were initiated to compare the risks and benefits of CAS with CEA. One of the earliest trials to compare endovascular and surgical treatments was the randomized Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS, 1992-1997). The study was conducted prior to the advent of embolic protection devices or self-expanding stents and found that endovascular treatment (balloon angioplasty or stenting) had similar major risks and effectiveness at preventing stroke over 3 years as compared with CEA and had less minor complications. In more recent randomized trials such as the International Carotid Stenting Study (ICSS, 2001-2008)10 and the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST, 2000-2008)12, currently available stents and embolic protection devices were utilized. In the ICSS study, the incidence of stroke, death or myocardial infarction was higher with CAS than CEA. This study concluded that most patients had no complications from either procedure and CAS outcomes were similar to those of CEA in previous trials. CAS was therefore regarded as a suitable treatment for patients unwilling or unable to have surgery because of anatomical or medical contraindications. However, the ICSS investigators stated that CEA should remain the treatment of choice for revascularization for patients suitable for surgery until the completion of the 3 year long-term follow-up. In the CREST study, there was a higher risk of stroke with stenting and higher risk of myocardial infarction with endarterectomy during the periprocedural period, but the effect on the quality of life was less than the effect of stroke. This study concluded that the risk of the composite primary outcome of stroke, myocardial infarction or death did not differ significantly in the group undergoing stenting or endarterectomy for patients with symptomatic and asymptomatic carotid stenosis. Hence, both treatment options are considered clinically robust, safe and effective. One important finding from the CREST trial is that the data demonstrated the need for improving embolic protection in the elderly to reduce the stroke rate.

The SAPPHIRE randomized trial (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) compared carotid stenting using distal emboli protection device (EPD) with carotid endarterectomy in patients specifically at high surgical risk13. Although the trial was stopped prematurely due to slow enrollment in patients with symptomatic stenosis, the occurrence of primary endpoint (composite of stroke, myocardial infarction (MI) or death) was similar (16.8% in CAS vs. 16.5% in CEA). In asymptomatic patients, fewer primary endpoints occurred after CAS (9.9% vs. 21.5%). In contrast to SAPPHIRE, the EVA-3S study (Endarterectomy Versus Angioplasty in Patients with Severe Symptomatic Carotid Stenosis) was terminated prematurely due to a significant difference in the 30-day complication rate favoring carotid surgery14. The EVA- 3S data demonstrated the need for low profile devices to increase the ease of use. Over time, the technique and technology involved in carotid artery stenting has advanced due to dual layer development to prevent plaque prolapse and ease of use elements along with recapture capabilities, flexibility and compatibility with commercial filters and 5.0 French systems. Animal lab experiments have also shown lack of significant re-stenosis, stent thrombosis and endothelialization.

The current clinical study is being initiated to evaluate the safety and efficacy of MicroVention Roadsaver™ Carotid Stent device used in conjunction with the Nanoparasol® embolic protection system for the treatment of carotid artery stenosis in patients with elevated risk for adverse events following carotid endarterectomy.

Clinical Study Identifier: TX143858

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