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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

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Year of Publication: 2017

Authors: Raul G. Nogueira, MD; Donald Frei, MD; Jawad F. Kirmani, ..., MD; Adnan Siddiqui

Journal: JAMA Neurology

Citation: JAMA Neurol. 2018:75(3):304-311. doi:10.1001/jamaneurol.2017.3967

Link: https://doi.org/10.1001/jamaneurol.2017.3967

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

Content summarized and formatted by NeuroTrials.ai.

Penumbra Separator 3D

(2017)

Objective

To evaluate whether the use of the Penumbra 3D Revascularization Device in conjunction with aspiration thrombectomy improves angiographic and clinical outcomes compared to aspiration thrombectomy alone in patients with acute ischemic stroke.

Study Summary

• The addition of the Penumbra Separator 3D device to aspiration thrombectomy improved first-pass revascularization rates and reduced the number of passes needed, without increasing adverse events.

Intervention

Randomized controlled trial comparing aspiration thrombectomy alone vs. aspiration thrombectomy plus the Penumbra Separator 3D device in patients with anterior circulation large-vessel occlusion stroke within 8 hours of symptom onset.

Inclusion Criteria

Patients with acute ischemic stroke due to anterior circulation large-vessel occlusion (ICA or M1), NIHSS ≥ 8, ASPECTS ≥ 6, and within 8 hours of symptom onset.

Study Design

Arms: Aspiration thrombectomy alone vs. aspiration thrombectomy + Penumbra Separator 3D device.

Patients per Arm: 3D Device: 81, Aspiration alone: 83

Outcome

• Primary angiographic endpoint (TICI 2–3 revascularization after first pass): 3D group 61% vs. control 42% (P = .02); • Final TICI 2b–3 revascularization: 88% in 3D vs. 79% in control (P = .17); • 90-day mRS 0–2: 63% in 3D group vs. 56% in control (P = .36); • Median number of passes: fewer in 3D group (P = .001); • Embolization to new territory: lower in 3D group (0%) vs. control (6%); • Symptomatic ICH: similar between groups (3% vs. 2%).

Bottom Line

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.

Study Design

Study Type: Prospective, randomized, single-blinded, active controlled, noninferiority, multicenter trial.
Randomization: Yes
Blinding: Adjudicators of the primary end points and imaging core laboratory were masked to treatment allocation; treating investigators were not masked.
Sample Size: 198
Follow-up: 90 days.
Centers: 25
Countries: United States

Primary Outcome

Definition: 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.

Control	Intervention	HR/OR	P-value
82.3% (79/96)	87.2% (82/94)	- (-3.6% to 13.5% (90% CI for Risk Difference))	Non-inferiority met (lower bound of 90% CI > -15%)

Limitations & 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.

Citation

JAMA Neurol. 2018:75(3):304-311. doi:10.1001/jamaneurol.2017.3967

View Original Publication →

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

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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