PDF: Penumbra
(2009)Objective
To assess the safety and effectiveness of the Penumbra System, a new mechanical thrombectomy device, for revascularizing large vessel occlusions in acute ischemic stroke patients within 8 hours of onset.
Study Summary
• Symptomatic intracranial hemorrhage occurred in 11.2% of patients.
• Despite the high revascularization rate, only 25% of patients achieved a good functional outcome (mRS ≤2) at 90 days, a notable disparity.
Intervention
Mechanical thrombectomy using the Penumbra System (aspiration and/or extraction) within 8 hours of stroke symptom onset in patients with large vessel occlusion. Clinical follow-up was for 90 days.
Study Design
Arms: Array
Outcome
• Good functional outcome (mRS ≤2) at 90 days was seen in 25% of all patients (29% of those revascularized vs. 9% of those not).
• 90-day mortality was 32.8%.
• The rate of symptomatic intracranial hemorrhage was 11.2%.
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.
Study Design
- Study Type
- Prospective, multicenter, single-arm trial
- Randomization
- No
- 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.
- Sample Size
- 125
- Follow-up
- 90 days
- Centers
- 24
- Countries
- United States, Europe
Primary Outcome
Definition: Rate of successful revascularization, defined as achieving TIMI grade 2 or 3 flow in the target vessel after the procedure.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 81.6% (102/125) | - |
Limitations & 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.
Citation
Stroke. 2009;40:2761-2768.