Safety and Efficacy of a 3-Dimensional Stent Retriever With Aspiration-Based Thrombectomy vs Aspiration-Based Thrombectomy Alone in Acute Ischemic Stroke Intervention: A Randomized Clinical Trial

Abstract

Importance: The treatment effects of individual mechanical thrombectomy devices in large-vessel acute ischemic stroke (AIS) remain unclear.

Objective: To determine whether the novel 3-dimensional (3-D) stent retriever used in conjunction with an aspiration-based mechanical thrombectomy device (Penumbra System; Penumbra) is noninferior to aspiration-based thrombectomy alone in AIS.

Design, setting, and participants: This randomized, noninferiority clinical trial enrolled patients at 25 North American centers from May 19, 2012, through November 19, 2015, with follow-up for 90 days. Adjudicators of the primary end points were masked to treatment allocation. Patients with large-vessel intracranial occlusion AIS presenting with a National Institutes of Health Stroke Scale (NIHSS) score of at least 8 within 8 hours of onset underwent 1:1 randomization to 3-D stent retriever with aspiration or aspiration alone. The primary analyses were conducted in the intention-to-treat population.

Interventions: Mechanical thrombectomy using intracranial aspiration with or without the 3-D stent retriever.

Main outcomes and measures: The primary effectiveness end point was the rate of a modified Thrombolysis in Cerebral Infarction (mTICI) grade of 2 to 3 with a 15% noninferiority margin. Device- and procedure-related serious adverse events at 24 hours were the primary safety end points.

Results: Of 8082 patients screened, 198 patients were enrolled (111 women [56.1%] and 87 men [43.9%]; mean [SD] age, 66.9 [13.0] years) and randomized, including 98 in the 3-D stent retriever with aspiration group and 100 in the aspiration alone group; an additional 238 patients were eligible but not enrolled. The median baseline NIHSS score was 18.0 (interquartile range, 14.0-23.0). Eighty-two of 94 patients in the 3-D stent retriever and aspiration group (87.2%) had an mTICI grade of 2 to 3 compared with 79 of 96 in the aspiration alone group (82.3%; difference, 4.9%; 90% CI, -3.6% to 13.5%). None of the other measures were significantly different between the 2 groups. Device-related serious adverse events were reported by 4 of 98 patients in the 3-D stent retriever with aspiration group (4.1%) vs 5 of 100 patients in the aspiration only group (5.0%); procedure-related serious adverse events, 10 of 98 (10.2%) vs 14 of 100 (14.0%). A 90-day modified Rankin Scale score of 0 to 2 was reported by 39 of 86 patients in the 3-D stent retriever with aspiration group (45.3%) vs 44 of 96 patients in the aspiration only group (45.8%).

Conclusions and relevance: The present study provides class 1 evidence for the noninferiority of the 3-D stent retriever with aspiration vs aspiration alone in AIS. Future trials should evaluate whether these results can be generalized to other stent retrievers.

Trial registration: clinicaltrials.gov Identifier: NCT01584609.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Frei reports a consulting relationship with Penumbra, Inc, and stock ownership. Dr Turk reports research grants and personal fees from Penumbra, Inc. Dr Heck reports receiving consultant fees from Stryker and investigator payments from Penumbra, Inc. Dr Levy reports personal fees and ownership interest from Intratech Medical, Ltd, and Blockade Medical, LLC, ownership interest and advisory board membership from NeXtGen Biologics, serving as national principal investigator from Covidien SWIFT PRIME Trials, honorarium from Covidien AKA Medtronic, consultant fees from Pulsar and Blockade Medical, LLC, training fees from Abbott, serving on the AIS clinical advisory board of Stryker, serving on the advisory board of MEDX, and serving as an expert witness from Renders Medical/Legal Opinions. Dr Dörfler reports personal fees from Penumbra, Inc. Dr Yoo reports a research grant from Penumbra, Inc, and a consulting relationship with Neuravi. Dr Derdeyn reports stock options from Pulse Therapeutics and fees from Silk Road as chairperson of the DSMB. Drs Derdeyn, Schwamm, and Langer served as members of the DSMB for this study, for which they received fees from Penumbra. No other disclosures were reported.

Figures

Figure 1.. CONSORT Flow Diagram

mRS indicates modified Rankin Scale; 3-D, 3-dimensional.

Figure 2.. Primary and Key Secondary End Point Differences Between Treatment Groups

ICH indicates intracranial hemorrhage; mRS, modified Rankin Scale; mTICI, modified Thrombolysis in Cerebral Infarction; and 3-D, 3-dimensional. aIndicates primary end point (with 90% CI). bIndicates post hoc end point (with 90% CI). cIndicates secondary end point (with 95% CI).