← Back

Penumbra

The Penumbra Pivotal Stroke Trial: Safety and Effectiveness of a New Generation of Mechanical Devices for Clot Removal in Intracranial Large Vessel Occlusive Disease

Share Share Copied! Compare

Year of Publication: 2009

Authors: The Penumbra Pivotal Stroke Trial Investigators

Journal: Stroke

Citation: Stroke. 2009;40:2761-2768.

Link: https://tinyurl.com/4pr4av9z

PDF: https://tinyurl.com/4pr4av9z

Clinical Question

To assess the safety and effectiveness of the Penumbra System in the revascularization of patients presenting with acute ischemic stroke secondary to intracranial large vessel occlusive disease within 8 hours of symptom onset.

Bottom Line

The Penumbra System demonstrated a high rate of successful revascularization (81.6%) in acute ischemic stroke patients with large vessel occlusions. While the procedure appeared safe, with rates of complications and hemorrhage comparable to historical controls, the high revascularization rate did not translate into a correspondingly high rate of good functional outcome at 90 days.

        Major Points
        This was a prospective, multicenter, single-arm study that enrolled 125 patients with acute ischemic stroke due to large vessel occlusion who were treated within 8 hours of symptom onset.
The primary effectiveness endpoint was successful revascularization (TIMI grade 2 or 3), which was achieved in 81.6% of treated vessels.
The rate of symptomatic intracranial hemorrhage (sICH) at 24 hours was 11.2%.
At 90 days, 25% of patients achieved a good functional outcome (modified Rankin Scale score ≤2), and the all-cause mortality rate was 32.8%.
Successful revascularization was associated with better neurological outcomes and a trend toward lower mortality, but the overall rate of good functional outcome was lower than might be expected given the high revascularization rate.
The trial was designed to demonstrate substantial equivalence to the MERCI device for FDA 510(k) clearance, not superiority over medical management.

      

Design

Study Type: Prospective, multicenter, single-arm trial

Randomization:

Blinding: This was an open-label study. Angiographic and CT scan data were adjudicated by a blinded, independent core laboratory. Safety events were adjudicated by a Clinical Events Committee.

Enrollment Period: June 2006 to June 2007

Follow-up Duration: 90 days

Centers: 24

Countries: United States, Europe

Sample Size: 125

Analysis: Descriptive statistics were used. Outcomes were compared between patients with successful versus unsuccessful revascularization using a 2-tailed Fisher exact test. The primary effectiveness endpoint was compared to historical controls.

Inclusion Criteria

Presentation within 8 hours of symptom onset
National Institutes of Health Stroke Scale (NIHSS) score ≥8
Angiographically verified occlusion (Thrombolysis In Myocardial Infarction [TIMI] Grade 0 or 1) of a large intracranial vessel
Patients presenting within 3 hours must have been ineligible for or refractory to intravenous recombinant tissue plasminogen activator (tPA) therapy

Exclusion Criteria

Extensive infarction greater than one third of the middle cerebral artery (MCA) territory
Severe edema or intracranial hemorrhage (ICH) on baseline imaging
Pregnancy

Baseline Characteristics

Characteristic	Control	Active
Group		Overall Population (n=125)
Age, years (mean±SD)		63.5±13.5
Female, %		49
NIHSS (mean±SD)		17.6±5.2
Target vessel - MCA, %		70
Target vessel - ICA, %		18
Time to arterial puncture, hours (mean±SD)		4.3±1.5

Arms

Field	Mechanical Thrombectomy with Penumbra System
Intervention	Revascularization procedure using the Penumbra System, which combines thrombus debulking via aspiration with an option for direct thrombus extraction.
Duration	Single procedure

Outcomes

Outcome	Type	Control	Intervention	P-value
Rate of successful revascularization, defined as achieving TIMI grade 2 or 3 flow in the target vessel after the procedure.	Primary		81.6% (102/125)
Good clinical outcome (mRS ≤2) at 90 days	Secondary	9% (Not Revascularized)	29% (Revascularized)	0.0596
Death at 90 days	Secondary	48% (Not Revascularized)	29% (Revascularized)	0.1384
Symptomatic intracranial hemorrhage (at 24h)	Adverse		11.2% (14/125)
Any intracranial hemorrhage (at 24h)	Adverse		28% (35/125)
Serious procedural events	Adverse		2.4% (3/125)
All-cause mortality at 90 days	Adverse		32.8%

Subgroup Analysis

Multivariate analysis identified lower baseline NIHSS score as a predictor of good functional outcome, while higher baseline NIHSS, history of CVA, and site of occlusion were predictors of mortality.

Criticisms

The study was a single-arm trial that lacked a concurrent control group, making it impossible to definitively conclude that the intervention improved functional outcomes compared to medical management alone.
There was a notable disparity between the very high revascularization rate (81.6%) and the modest rate of good functional outcome at 90 days (25%), the cause of which remains unclear from this study.
Patient selection was not guided by advanced imaging (eg, perfusion scans) to confirm the presence of salvageable ischemic penumbra, which may have contributed to the modest clinical outcomes despite successful revascularization.

Funding

Penumbra Inc.

Based on: Penumbra (Stroke, 2009)