Penumbra Separator 3D
Safety and Efficacy of a 3-Dimensional Stent Retriever With Aspiration-Based Thrombectomy vs Aspiration-Based Thrombectomy Alone in Acute Ischemic Stroke Intervention
Clinical Question
In patients with acute ischemic stroke from large-vessel occlusion, is mechanical thrombectomy using the 3-D stent retriever in conjunction with aspiration noninferior to aspiration-based thrombectomy alone?
Bottom Line
In patients with acute ischemic stroke, mechanical thrombectomy using the 3-D stent retriever with aspiration was noninferior to aspiration alone in achieving successful revascularization. Rates of device- and procedure-related serious adverse events and 90-day functional outcomes were similar between the two groups.
Major Points
- This was a randomized, noninferiority clinical trial comparing a combination of a 3-D stent retriever with aspiration versus aspiration alone for mechanical thrombectomy in large-vessel occlusion stroke.
- The primary effectiveness endpoint of successful revascularization (mTICI grade 2-3) was achieved in 87.2% of the combination therapy group versus 82.3% of the aspiration-alone group, meeting the criteria for noninferiority (difference, 4.9%; 90% CI, -3.6% to 13.5%).
- Rates of device-related serious adverse events (4.1% vs 5.0%) and procedure-related serious adverse events (10.2% vs 14.0%) were not significantly different between the combination and aspiration-alone groups, respectively.
- There was no significant difference in the rate of good functional outcome (mRS 0-2) at 90 days (45.3% vs. 45.8%).
- The trial provides Class 1 evidence for the noninferiority of the 3-D stent retriever with aspiration compared to aspiration alone.
Design
Study Type: Prospective, randomized, single-blinded, active controlled, noninferiority, multicenter trial.
Randomization: 1
Blinding: Adjudicators of the primary end points and imaging core laboratory were masked to treatment allocation; treating investigators were not masked.
Enrollment Period: May 19, 2012, through November 19, 2015.
Follow-up Duration: 90 days.
Centers: 25
Countries: United States
Sample Size: 198
Analysis: The primary analyses were conducted in the intention-to-treat population.
Inclusion Criteria
- Age 18 to 85 years.
- Symptoms consistent with an acute ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score of at least 8.
- Arterial puncture expected within 8 hours from symptom onset.
- Radiographically demonstrated large-vessel occlusion (≥2.5 mm in diameter) in the intracranial circulation.
- Refractory to or not eligible for intravenous alteplase therapy.
Exclusion Criteria
- Exclusion criteria are described in the eMethods in Supplement 2 and not detailed in the main manuscript.
Arms
| Field | Control | 3-D Stent Retriever with Aspiration |
|---|---|---|
| Intervention | Mechanical thrombectomy using an aspiration-based device alone (Penumbra System). The procedure involved using an appropriately sized reperfusion catheter to remove the clot via pump aspiration. | Mechanical thrombectomy using the Penumbra 3-D stent retriever in conjunction with an aspiration-based mechanical thrombectomy device (Penumbra System). |
| Duration | Procedure | Procedure |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| The primary effectiveness endpoint was the rate of successful angiographic revascularization of the occluded target vessel, defined as a modified Thrombolysis in Cerebral Infarction (mTICI) grade of 2 to 3. | Primary | 82.3% (79/96) | 87.2% (82/94) | 4.94% | Non-inferiority met (lower bound of 90% CI > -15%) |
| Functional independence (mRS score 0-2) at 90 days | Secondary | 45.8% (44/96) | 45.3% (39/86) | Difference, -0.5% (95% CI, -15.0% to 14.0%) | >0.99 |
| All-cause mortality at 90 days | Secondary | 26.0% (26/100) | 19.4% (19/98) | Difference, -6.6% (95% CI, -18.24% to 5.01%) | 0.31 |
| Symptomatic intracranial hemorrhage (ICH) within 24h | Secondary | 5.0% (5/100) | 3.1% (3/98) | Difference, -1.9% (95% CI, -7.40% to 3.53%) | 0.72 |
| Device-related serious adverse event at 24h | Adverse | 5.0% (5/100) | 4.1% (4/98) | Difference, -0.92% (95% CI, -6.71% to 4.88%) | |
| Procedure-related serious adverse event at 24h | Adverse | 14.0% (14/100) | 10.2% (10/98) | Difference, -3.80% (95% CI, -12.86% to 5.27%) |
Subgroup Analysis
There was no evidence of any significant heterogeneity of treatment effect in any of the prespecified subgroups (age <65 or ≥65 years, baseline NIHSS score <20.0 or ≥20.0, and site of occlusion).
Criticisms
- Investigators were not masked to the treatment arm, although the primary trial endpoints were adjudicated by masked core laboratory staff.
- The primary efficacy endpoint of mTICI 2-3 was less stringent than the current standard of mTICI 2b-3, though a post hoc analysis suggested the noninferiority requirements would have still been met with the stricter definition.
- The results are specific to the 3-D stent retriever and should not be extrapolated to other stent retriever devices.
- The noninferiority margin of 15% may have been too wide, as such a difference in reperfusion could potentially lead to different clinical outcomes.
Funding
This study was supported by Penumbra, Inc.
Based on: Penumbra Separator 3D (JAMA Neurology, 2017)
Authors: Raul G. Nogueira, MD; Donald Frei, MD; Jawad F. Kirmani, ..., MD; Adnan Siddiqui
Citation: JAMA Neurol. 2018:75(3):304-311. doi:10.1001/jamaneurol.2017.3967
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