Safety and efficacy results of the Flow Redirection Endoluminal Device (FRED) stent system in the treatment of intracranial aneurysms: US pivotal trial

Abstract

ObjectiveTo evaluate the safety and effectiveness of the Flow Redirection Endoluminal Device (FRED) flow diverter in support of an application for Food and Drug Administration approval in the USA.Methods145 patients were enrolled in a prospective, single-arm multicenter trial. Patients with aneurysms of unfavorable morphology for traditional endovascular therapies (large, wide-necked, fusiform, etc) were included. The trial was designed to demonstrate non-inferiority in both safety and effectiveness, comparing trial results with performance goals (PGs) established from peer-reviewed published literature. The primary safety endpoint was death or major stroke (National Institutes of Health Stroke Scale score ≥4 points) within 30 days of the procedure, or any major ipsilateral stroke or neurological death within the first year. The primary effectiveness endpoint was complete occlusion of the target aneurysm with ≤50% stenosis of the parent artery at 12 months after treatment, and in which an alternative treatment of the target intracranial aneurysm had not been performed.Results145 patients underwent attempted placement of a FRED device, and one or more devices were placed in all 145 patients. 135/145 (93%) had a single device placed. Core laboratory adjudication deemed 106 (73.1%) of the aneurysms large or giant. A safety endpoint was experienced by 9/145 (6.2%) patients, successfully achieving the safety PG of <15%. The effectiveness PG of >46% aneurysm occlusion was also achieved, with the effectiveness endpoint being met in 80/139 (57.6%)ConclusionAs compared with historically derived performance benchmarks, the FRED flow diverter is both safe and effective for the treatment of appropriately selected intracranial aneurysms.Clinical registration numberNCT01801007

The Pennsylvania Postmarket Multicenter Experience With Flow Redirection Endoluminal Device

“…Because aneurysmal size has been reported as a negative predictor of aneurysmal occlusion after flow diversion, [13][14][15] the lower rates of occlusion in the US Pivotal Trial might be, at least partially, attributed to the larger size of the aneurysms in the study (73% ≥10 mm vs 32% ≥10 mm in our data). Moreover, the lack of independent core laboratory adjudication and availability of DSA follow-up imaging in just more than 2/3 of the patients (69.4%; vs 100% in the US Pivotal study 6 ) might have exaggerated our occlusion rates and represents an inherent limitation to this work. The safety of the FRED system is reinforced in our experience, evidently by the low rate of permanent disabling stroke encountered in 1 patient (1.4%) without procedural mortality, comparable with the other major device studies, 3,4,6 and data from other literature series with average ischemic complications of 3.8%.…”

“…9 Our results further reiterate the device's safety and efficacy, in line with the overall aggregate literature documenting the favorable results of the FRED system, [3][4][5] albeit comparing slightly favorably with the recently published US Pivotal Trial that granted the FDA approval for the FRED device. 6 The multicenter investigational device exemption study evaluated a total of 145 patients from 23 US centers harboring intracranial aneurysms deemed of unfavorable morphology for traditional endovascular techniques. Primary end points included complete aneurysmal occlusion in 57.6% of cases and composite safety end point of major stroke or death up to the first year observed in 6.2% of the patients.…”

“…Primary end points included complete aneurysmal occlusion in 57.6% of cases and composite safety end point of major stroke or death up to the first year observed in 6.2% of the patients. 6 These results are on the lower side compared with the pipeline for uncoilable or failed aneurysms trial results. However, the FRED system's long-term efficacy remains unclear, given the known time-dependent aneurysmal obliteration with flow diversion.…”

Delayed aneurysm rupture in a patient treated with flow redirection endoluminal device: A case report and literature review

“…According to our literature review, six cases of delayed rupture of aneurysms caused by the placement of a FRED have been reported. [ 11 , 14 , 15 , 17 ] Based on these previous reports, the incidence of delayed rupture of intracranial aneurysm after placement of a FRED is believed to be 0.3–1.3%. Including our case, seven cases of delayed rupture of aneurysm after placement of a FRED have been reported to date [ Table 1 ].…”

Time to recognize three classes of non-inferiority trial margins

“…Non-inferiority trials are a staple of neuroendovascular research 1. Many of the tools neurointerventionalists employ daily received regulatory approval and guideline support through performance of non-inferiority trials, including stent retriever and aspiration mechanical thrombectomy devices for acute ischemic stroke,2–4 coils and flow diverter stents for intracranial aneurysms,5 6 and liquid embolic agents for cerebral arteriovenous malformations 7…”