Background and purpose Revascularization of acute ischemic stroke from a large vessel occlusion continues to be a challenge with current thrombectomy devices. The purpose of the SPEED study was to report the safety and effectiveness of the Penumbra 054 Reperfusion Catheter System in revascularizing large vessel occlusions.
Methods In this retrospective multicenter study, data were collected from patients with angiographic evidence of large vessel occlusion treated with the Penumbra 054 device as the intended primary therapy. Clinical outcome data were collected with 90-day follow-up and the results were compared with those from the Penumbra Pivotal trial.
Results Eighty-seven target vessels in 86 consecutive patients treated with the Penumbra 054 device were included. The Thrombolysis In Myocardial Infarction (TIMI) 2 or 3 revascularization rate was 91% compared with a reported 82% in the Penumbra Pivotal trial. This was accomplished in a median time of 20 min compared with 45 min in the Penumbra Pivotal trial (p<0.0001). Eighteen (21%) patients experienced an intracranial hemorrhage of which 12 (14%) were symptomatic. Good neurologic outcome (modified Rankin scores ≤ 2) at 90-day follow-up was achieved in 34.9% of patients compared with 25% reported in the Penumbra Pivotal trial. All-cause mortality was 25.6%.
Conclusions These results suggest that the Penumbra 054 is a fast, safe and effective revascularization tool for patients experiencing ischemic stroke secondary to large vessel occlusive disease. Improvements in speed and effectiveness of revascularization probably contributed to improved outcomes.
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In the USA approximately 795 000 patients experience a new or recurrent stroke each year.1 Of these, 87% are ischemic in nature, many involving thromboembolic occlusion of a major cerebral artery. Substantial evidence in the published literature suggests that mortality and morbidity associated with ischemic stroke can be prevented with early and safe revascularization of the primary occlusion.2–4 Thus, the need for revascularization techniques that are fast as well as safe and effective is paramount to combat the mortality and morbidity associated with this disease.
The Penumbra System (Penumbra, Alameda, California, USA) is a neuroembolectomy device specifically designed to remove thrombus by aspiration.5 ,6 It received 510(k) clearance from the US FDA for an acute ischemic stroke revascularization indication in 2008. The initial trial for this clearance was a prospective single-arm study in 125 patients designed to assess the safety and effectiveness of the Penumbra System. The Merci Retriever (Concentric Medical, Mountain View, California, USA) was used as the predicate device (historical control).5 While achieving high rates of recanalization (82%), the number of patients with good neurologic outcomes was lower than expected (25%). The results of the subsequent POST Study, performed after operators had greater clinical experience with the device, expanded on these results and a good functional outcome at 90 days was achieved in 41% of the 157 patients enrolled.6 However, treatment of large proximal vessel occlusions continued to be a challenge due to a number of causes, one of which could be the limited aspiration capacity with the available devices.
The Penumbra 054 Reperfusion Catheter/Separator received 510(k) clearance in September 2009. This addition to the Penumbra System family was designed to increase aspiration efficiency through a larger internal catheter diameter and to address large clot burdens in proximal vessels such as the internal carotid artery (ICA). This report details a multicenter initial experience to determine the safety and effectiveness of the 054 Reperfusion Catheter (the SPEED study).
Materials and methods
Under a universal protocol approved by each local Internal Review Board, data were collected in a retrospective fashion from consecutive patients with acute stroke who had been treated with the Penumbra 054 catheter. The SPEED study was a multicenter retrospective case review performed in Europe and the USA. Centers were selected based on the routine use of the Penumbra 054 Reperfusion Catheter in the treatment of acute ischemic stroke.
With the addition of the 054 catheter, the Penumbra System consists of four sizes of reperfusion catheters and separators identified by their distal internal diameters: 0.054 inch, 0.041 inch, 0.032 inch and 0.026 inch. Patients enrolled in the study met the main inclusion criteria of presenting with acute ischemic stroke within 8 h of symptom onset from a large vessel occlusion and treated with the Penumbra 054 Reperfusion Catheter as the primary therapy. Patients with non-contrast CT evidence of intracranial hemorrhage before treatment or who were treated off-label were not included.
The effectiveness of the Penumbra System with the 054 device was measured in accordance with Thrombolysis In Myocardial Infarction (TIMI) flow classification adopted for cerebral vasculature using digital subtraction angiography.2 ,7 ,8 TIMI flow was selected in order to allow a fair comparison with the revascularization rate reported in the Penumbra Pivotal trial, which was Core Lab adjudicated. Prior to treatment with the Penumbra 054 catheter, all patients were required to have angiographic documentation of TIMI 0 or TIMI I flow in the target large vessel. Revascularization was assessed after treatment with the Penumbra 054 catheter but before the initiation of any adjunctive therapies. The time of revascularization for both studies was defined as the time from aspiration initiation to final aspiration use.
Data collected at hospital admission also included patient's medical history as well as neurological status using the National Institutes of Health Stroke Scale (NIHSS). NIHSS scores and modified Rankin scores (mRS) were collected 7 days after the procedure, at discharge and 90 days after the procedure. All serious adverse events (SAEs) that occurred between the time of the procedure and 90 days after were reported.
Primary endpoints included the rates of successful recanalization immediately after the procedure (TIMI score 2 or 3), all procedural SAEs inclusive of intracerebral hemorrhage (ICH) at 24 h after the procedure as reported by the site investigator and the median time of revascularization. For the purposes of analysis, symptomatic ICH was defined as evidence of hemorrhage from imaging within 24 h after the procedure with an increase in the NIHSS score to ≥4. A secondary study objective was also to determine if there is a correlation between time to revascularization and functional independence at 90 days post-procedure as defined by mRS scores of 0–2.9
For numeric measures, standard descriptive statistics were employed for each endpoint. The size (n), mean, median (where appropriate) and standard deviations were reported. The non-parametric Wilcoxon rank-sum test was used to test for a two-sided difference in the median values between each trial. The α level for significance was set at 0.05.
For categorical outcomes the number and percentage were reported for each endpoint using the total study cohort as the denominator. The Fisher exact test was used for a two-sided comparison of association of categorical outcomes at each endpoint. The α level for significance was set at 0.05.
From 2010 to 2011, 86 eligible patients at 11 international sites were treated with the Penumbra 054 device. The baseline characteristics of the patients in the SPEED study were comparable to those in the Pivotal trial (table 1). Patients in the Penumbra 054 cohort appeared to have a larger percentage of women (NS) and a significantly greater median time from symptom onset to arterial puncture (p=0.021). The 054 catheter achieved TIMI 2 or 3 revascularization in 90.8% of patients (60.9% TIMI 2 and 29.9% TIMI 3) compared with 81.6% of the patients in the Pivotal trial (table 2). This was independent of target vessel location and revascularization, with the Penumbra 054 catheter being successful in 96.2% of ICA occlusions and 87.5% of middle cerebral artery (MCA) occlusions (table 3).
Eighteen patients (21%) experienced an ICH of which 12 (14%) were symptomatic (table 2). Four procedural SAEs were reported in three patients (3.5%). These included catheter perforation, microwire perforation, vasospasm or distal embolus. The one catheter perforation was attributed to a 032 catheter used in the distal vasculature during thrombectomy. There was one report of a kinked 054 catheter.
Good clinical outcome, defined as 90-day mRS ≤ 2, was achieved by 22 (34.9%) of the 63 treated patients (table 2). All-cause mortality was 25.6% (22/86). These patient outcomes are in contrast to a good patient outcome rate of 25% and 33% mortality in the Pivotal trial. The Penumbra System was comparable between target vessel revascularization and good patient outcome, but the total mortality in patients presenting with ICA primary occlusion was higher than in those with MCA occlusion (table 3). Patients who were successfully revascularized had a significantly lower likelihood of death than those who were not revascularized (table 4).
This study has shown that the new Penumbra 054 Reperfusion Catheter is safe and effective in removing thrombus from large cerebral vessels. The larger 054 Aspiration catheter was able to revascularize large proximal occluded cerebral vessels with similar rates of TIMI 2 or 3 and safety (complication, mortality and ICH rates) as previous reports using other Penumbra Aspiration devices. However, the significant finding was the speed at which recanalization was achieved, in less than half the time reported for smaller aspiration catheters. The ability to achieve recanalization on average in 20 min was also superior to that reported with the stent retriever Solitaire, for which recanalization was achieved in an average of 50 min.10
The primary observation of more rapid revascularization emphasizes the importance of using the largest aspiration catheter that will fit within the occluded target vessel. This allows maximal local aspiration capabilities and probably also results in fewer and smaller downstream emboli. Although similar rates of overall recanalization were observed, notably the recanalization rate of 91% in the current study was primarily with the use of the 054 aspiration catheter. While it is difficult to compare directly the SPEED study with Core Lab adjudicated trials, the Pivotal trial often required the full spectrum of the Penumbra family to achieve lower (82%) revascularization rates.
The rate of good functional outcomes (mRS ≤ 2) was 35% with the Penumbra 054 catheter, which compares favorably with the rate of 25% reported in the Pivotal trial. This occurred despite a 1 h difference in time to treatment. Good clinical outcomes were also similar to other reported device trials (36% in SWIFT, 40% in TREVO).10 ,11 When the effect of revascularization on good neurologic outcome was correlated there was a significant improvement in good outcome, with 36% of those revascularized doing well compared with 25% of those not revascularized. The likelihood of death is markedly greater (63%) in patients in whom revascularization is not achieved compared with those successfully revascularized (23%). This effect was similar to that reported in the Multi-Merci Trial which performed a similar analysis.12 This finding, which also corroborates the natural history of proximal large vessel occlusions, highlights the nearly universal poor outcome in these patients if left untreated.
Intracranial hemorrhage rates were found to be identical to those observed in the Pivotal trial (21%); however, more symptomatic hemorrhages were noted with the Penumbra 054 device than in the Pivotal trial (14% vs 11%). This rate is also similar, albeit slightly higher, than those reported in the PROACT II (10.9%) and Multi-Merci trials (9.8%).12 ,13 The procedural rate of SAEs was 3.5%, which is also similar to that reported in the Pivotal trial. Despite the slightly higher rate of symptomatic hemorrhage, the high degree of good clinical outcomes and low SAE rate found with the Penumbra 054 catheter validates the safety and effectiveness of the device.
The strength of this study is the international multicenter nature of the collaboration using numerous operators at multiple institutions around the world. The successful results achieved included the initial cases treated by the operators, suggesting that there is a learning curve for this device in operators with experience with the Penumbra System. Challenges and limitations of this study include the retrospective single-arm design with lack of Core Lab adjudication of recanalization rates and the fact that follow-up data were only available for 73% of the enrolled patients. This attrition rate in the SPEED trial may have an impact on the overall good functional outcome. The use of historic control data from the Pivotal Trial, while limited, uses data that the FDA deemed acceptable for 510(k) clearance of the Penumbra System in the USA. However, comparing outcomes from the use of the device in ‘real world’ everyday practice rather than those from highly selective patients enrolled in a regulatory prospective clinical trial may be problematic.
In summary, the Penumbra 054 Aspiration Catheter is a safe and highly effective device that is ideally suited for rapid revascularization of large proximal vessel occlusions. The outcomes found in this study are comparable to those reported in trials using currently using mechanical thrombectomy devices with a significant reduction in revascularization time. Larger prospective studies will be required to determine if this improvement in revascularization rates directly translates into improved clinical outcomes.
Contributors All authors made a material contribution to this article, revision of the article and the final approval of the article for submission to this journal.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.