The APOLLO PMS Study evaluated the safety of the Apollo™ Onyx™ Delivery Microcatheter used for delivery of the Onyx™ Liquid Embolic System during brain AVM embolization procedures.

Premature (unintentional) catheter tip detachment with clinical sequelae, catheter rupture/break/fracture with clinical sequelae, or retained catheter body in the vasculature were not observed in any of the subjects (0%), meaning the primary endpoint was met.

Premature (unintentional) catheter tip detachment was observed in 0.9% of subjects and intentional catheter tip detachment was observed in 60.7% of subjects. Catheter/tip leakage from detachment zone was not observed in any subjects (0%) through

a follow-up of 30 days. Also, migration of the retained catheter tip post embolization was not observed in any subjects (0%). Incidences of procedure-related adverse events were observed in 27.7% of subjects. However, in only 2 subjects (1.8%) the AEs observed through the 12-month follow-up were CEC-adjudicated as Apollo™ microcatheter-related.

Conclusion:
The findings from the APOLLO PMS Study provide evidence that the Apollo™ Onyx™ Delivery Microcatheter is safe to use for delivery of the Onyx™ LES during brain AVM embolization procedures.

The BARREL Study evaluated the safety and effectiveness of the Barrel® Vascular Reconstruction Device for Adjunctive Treatment to Embolic Coils for Wide-neck, Intracranial, Bifurcating/Branching Aneurysms of Middle Cerebral and Basilar Arteries.

The primary effectiveness endpoint (complete occlusion in the absence of retreatment, parent artery stenosis (>50%), or target aneurysm rupture at 12-month follow-up) and the primary safety endpoint (incidence of neurological death or major ipsilateral stroke 12-month post-procedure) were met. 

At 12-month follow-up, 93.9% of subjects met the composite mRS success of mRS 0-2 or no change from baseline. Also at 12 months, 

<25% of in-stent stenosis was reported in 98.8% and 25-50% in-stent stenosis was reported in 1.1% of subjects. None of the subjects reported >50% in-stent stenosis.

Conclusion:
The findings from the BARREL Study provide evidence that adjunctive treatment to embolic coils for wide-neck bifurcation/branching MCA and BA aneurysms with the Barrel™ VRD is safe and effective in that it results in good procedural success and complete aneurysm occlusion, with low complications, recurrence, and retreatment rates. The benefits of treatment are significant and outweigh the risk associated with its use.

The cAVM study is conducted at 22 French centers. Patients may be treated by embolization(s) only, embolization(s) + neurosurgery, or embolization(s) + radiosurgery. 

The primary objectives are to evaluate the safety (procedure- or device-related AEs up to 1 month post any embolization session) and performance (recovery rate at 12 months in the embolization 

alone and neurosurgery groups, and at 36 months in the radiosurgery group) of the Onyx® Liquid Embolic System. 

Enrollment was closed in Dec 2016; subject follow-up in the study is ongoing. Final study results are expected in 2021. 

The dAVF study was conducted at 25 French centers to evaluate the safety at 1 month and the performance at 1 month and 3 to 6 months post-embolization with the Onyx® Liquid Embolic System.

Good clinical outcome, indicated by mRS 0-2 changed from 86.8% at baseline to 92.3% at 1-month follow-up after last procedure. Notably, mRS 0 changed from 22% at baseline to 65.9% at 1-month follow-up after last procedure.

At a follow-up of 3-6 months of procedure 1 and 2, 84.7% and 71.4% of patients achieved healing/complete occlusion, 8.2% and 28.6% of patients achieved residual shunt type ≤ IIa; and 6.1% and 0% of patients had residual shunt type > IIa, respectively. Treatment failure was observed in one fistula (1.0%).

Within 1-month post-procedure, 31 CEC-adjudicated procedure- or Onyx™- related AEs were reported in 17.2% of patients. Of these, 30 procedure-related AEs were reported in 17.2% of patients, and 21 Onyx™-related AEs were reported in 11.2% of patients. (Except for one AE in one patient (0.9%), all AEs that were CEC-adjudicated as Onyx™-related were also adjudicated as procedure-related.)

Conclusion:
The results from the dAVF study provide evidence of the safe and efficient treatment of dural arteriovenous fistulae (dAVFs) with Onyx™ embolization. The benefits of treatment are significant and outweigh the risk associated with its use.

To purpose of the EMBOLISE study is to evaluate the safety and effectiveness of Onyx™ Liquid Embolic System (LES) embolization of the middle meningeal artery (MMA) as adjunct to conventional treatment (surgery or observation) for symptomatic subacute or chronic subdural hematoma.

The primary objective is to assess hematoma recurrence/progression requiring surgical drainage within 60 days post-treatment, comparing the experimental and control groups.

INSPIRE-A is a unique large scale, multi-device registry that aims to continuously assess SAFETY and measure EFFECTIVENESS of market released neurovascular products for the treatment of hemorrhagic stroke. In addition, the cumulatively collected high volume of patient data drives THERAPY EVIDENCE to support treatment paradigms in the rapidly evolving neurovascular therapy field.

Study endpoints are specific to the different devices, and include CLINICAL EVENTS COMMITTEE adjudicated SAFETY endpoints and independent CORE LABORATORY measured EFFECTIVENESS endpoints. INSPIRE-A was launched in December 2016 and - up

to May 2020 - includes >700 patients with Intracranial Aneurysms treated with the Pipeline™ FLEX, or Pipeline™ SHIELD, or Pipeline™ VANTAGE flow diverting devices. Patients are enrolled from 30 neurointerventional centers across Europe, Asia, Australia, Latin America, Middle East and Russia.

Interim analysis of the first 100 patients treated with the Pipeline Shield device, has shown great consistency with previous Pipeline studies. Efficacy and safety show excellent results, which are further specified in the September 09, 10.45h presentation at ESMINT 2020 by Prof I Szikora.

INSPIRE-S is a unique large scale, multi-device registry that aims to continuously assess SAFETY and measure EFFECTIVENESS of market released neurovascular products for the treatment of Acute Ischemic Stroke. In addition, the cumulatively collected high volume of patient data drives THERAPY EVIDENCE to support treatment paradigms in the rapidly evolving neurovascular therapy field.

Primary study endpoint is mRS at 90 days. Secondary objectives include CLINICAL EVENTS COMMITTEE adjudicated SAFETY endpoints; independent CORE LABORATORY measured EFFECTIVENESS endpoints; Health Economics outcomes.

INSPIRE-S was launched in May 2020. 1260 patients are planned to be enrolled from approximately 40 neurointerventional centers across the EMEA region. The study is comprised of 3 cohorts based on the first pass mechanical thrombectomy strategy applied:

• Aspiration only first pass
  
• Stent Retriever only first pass
  
• Combined use of Stent Retriever and Aspiration Catheter
  first pass

Interim results of this large-scale platform are regularly shared at various scientific meetings and conferences.

The LUNA study evaluated the safety and efficacy of the LUNA™ Aneurysm Embolization System. 63 subjects with bifurcation and sidewall aneurysms were enrolled. Most aneurysms were unruptured (60/63). 

Though immediate postoperative adequate occlusion was low (18%), adequate occlusion was achieved in 78.0% and 79.2% of the aneurysms at 12 months and 36 months, respectively. Four patients were retreated by the 12-month follow-up (6.3%) and three patients were retreated by the 36-month follow-up (4.8%). 

There were two major strokes (3.2%), one minor stroke (1.6%) and three incidents of intracranial hemorrhage in two subjects (3.2%) prior to the 12-month follow-up. There was one instance of mortality (1.6%).

Conclusion:
The results of the LUNA study demonstrate that the LUNA™ Aneurysm Embolization System is safe and effective for the treatment of bifurcation and sidewall aneurysms.

The (PFLEX) study was a prospective, single-arm, multicenter study for the treatment of unruptured IAs using the Pipeline™ Shield.
The primary endpoint was a major stroke in the territory supplied by the treated artery or neurologic death at 1-year post-procedure. Also, angiographic outcomes were assessed by an independent radiology laboratory at 6 months and 1 year.

Fifty patients with 50 unruptured IAs were treated. At 1-year post-procedure, no major strokes or neurologic deaths were reported, and complete occlusion was achieved in 81.8% of subjects.

There were no instances of aneurysm recurrence or retreatment. There were 6 cases of in-stent stenosis; all were asymptomatic
and non-serious.

Conclusion:
The angiographic and safety outcomes corroborate previous evidence that the Pipeline™ Shield is a safe and effective treatment for Intracranial Aneurysms.

PREMIER was the first prospective, multicenter trial to evaluate the use of the Pipeline™ device for the treatment of small and medium, unruptured aneurysms of the intracranial carotid and proximal vertebral artery. The study was conducted in 1 Canadian and 22 US centers. A total of 141 subjects with 141 target aneurysms were treated in the study.

Subject follow-up rates were high, with 98.6% (139/141) of subjects completing the 1-year clinical follow. Complete aneurysm occlusion without significant parent artery stenosis (≤ 50%) or retreatment of the target aneurysm 1-year post-procedure (primary effectiveness endpoint) occurred in 76.71% of subjects.

A total of 81.9% (113/138) aneurysms had complete occlusion, none (0%; 0/138) had aneurysm recurrence and 2.9% (4/139) had aneurysm retreatment at the 1-year follow-up.

Occurrence of major stroke in the territory supplied by the treated artery or neurological death at 1-year post-procedure (primary safety endpoint) occurred in 2.17% of subjects.

There were no major strokes in the territory supplied by the treated artery or neurological death at 30 days post-procedure due to procedural complications. Delayed intracerebral hemorrhage >30 days through 1-year post-procedure occurred in 0.73% of subjects. The overall mortality rate was 0.7% (1/141).

Conclusion:
Overall, a high rate of complete aneurysm occlusion was achieved with the use of the Pipeline™ device in the treatment of small/medium-sized wide-necked aneurysms. The incidence of major stroke, neurological death, and delayed intracerebral hemorrhage in the PREMIER study were low.

Therefore, results from the PREMIER Study demonstrated that the Pipeline™ device is effective and safe for the endovascular treatment of unruptured, small and medium, wide-necked intracranial aneurysms in the intracranial carotid and proximal vertebral artery.

The PUFs study evaluated the safety and effectiveness of the Pipeline™ device in large and giant, wide-necked intracranial aneurysms in the ICA.

107of the 108 enrolled subjects were treated with the Pipeline™ device. A total of 104 subjects with 106 aneurysms were included in the primary effectiveness cohort.

At 6-months, 73.6% of aneurysms achieved complete occlusion without major stenosis.

At 1-year, 86.8% were completely occluded, which increased through 3-years to 93.4% and 5-years to 95.2%.

There were no cases of aneurysm recurrence throughout the
five-year follow-up period.

The primary safety endpoint was the occurrence of ipsilateral major stroke or neurologic death at 6-months post-procedure, which occurred in 5.6% of subjects. No additional events of ipsilateral major stroke or neurological death were reported between 6-month and 5-year follow-up; therefore, the overall rate of ipsilateral major stroke or neurologic death remained 5.6%.

Conclusion:
Pipeline™ offers a safe and effective treatment of large or giant intracranial internal carotid artery aneurysms, demonstrated by high rates of complete aneurysm occlusion and low rates of
adverse neurologic events; even in aneurysms failing previous alternative treatments.

The SHIELD study assessed the performance of the Pipeline™ Flex Embolization Device with Shield Technology™ in subjects undergoing treatment for intracranial aneurysms in a large
real-world, post-market setting.

The primary effectiveness endpoint (complete occlusion without significant parent artery stenosis (≤ 50% stenosis) or retreatment of the target aneurysm through 1 year post-procedure) and the primary safety endpoint (occurrence of major stroke in the territory supplied by the treated artery or neurological death through 1 year post-procedure) were met in all populations. In addition there was no aneurysm recurrence through the 1-year follow-up and no target aneurysm rupture at peri-procedure.

Conclusion:
The results of the SHIELD study demonstrate that the benefits of aneurysm treatment with the Pipeline™ Shield device outweigh the risk associated with the procedure in all studied populations.

The STRATIS Registry evaluated the use of Medtronic market-released neurothrombectomy devices in patients diagnosed
with an acute ischemic stroke due to Large Vessel Occlusion.

Core laboratory–assessed substantial reperfusion was achieved
in 87.9% of cases with evaluable postprocedure angiograms.
Emboli to new vascular territory were observed in 0.8% of patients.
At 24-hour follow-up, the incidence of sICH was 1.4%.

At 90-day follow-up, good functional outcome (mRS score 0–2)
was achieved in 56.5% of patients and excellent functional outcome (mRS score 0–1) in 43.2% of patients.

Conclusion:
Real-world data shows that the use of Solitaire™ and MindFrame Capture™ LP Revascularization devices is safe, and achieves good reperfusion rates and functional outcome in patients with acute ischemic stroke due to Large Vessel Occlusion.

This large registry documents that the results of the randomized trials can be reproduced in real world practice.

The SWIFT PRIME study compared the functional outcomes
in acute ischemic stroke (AIS) subjects treated with either IV
t-PA alone or IV t-PA in combination with the Solitaire™
revascularization device.

The study was stopped early because of efficacy. 196 patients underwent randomization (98 patients in each group) in 39 sites in the United States and 6 European countries.

In the intervention group, the rate of substantial reperfusion at the end of the procedure was 88%. Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale (P<0.001).

The rate of functional independence (mRS 0 to 2) was higher in the intervention group than in the control group (60% vs. 35%, P<0.001). There were no significant between-group differences in 90-day mortality (9% vs. 12%, P=0.50) or symptomatic intracranial hemorrhage (0% vs. 3%, P=0.12)

Conclusion:
In patients receiving intravenous t-PA for acute ischemic stroke with confirmed large-vessel occlusions of the anterior circulation, treatment with the Solitaire™ stent thrombectomy device within 6 hours after symptom onset improved functional outcomes at 90 days.