Partial aortic occlusion for cerebral perfusion augmentation: safety and efficacy of NeuroFlo in Acute Ischemic Stroke trial

BACKGROUND AND PURPOSE: Fewer than 5% of patients with acute ischemic stroke are currently treated, and there is need for additional treatment options. A novel catheter treatment (NeuroFlo) that increases cerebral blood flow was tested to 14 hours. METHODS: The Safety and Efficacy of NeuroFlo in Acute Ischemic Stroke trial is a randomized trial of the safety and efficacy of NeuroFlo treatment in improving neurological outcome versus standard medical management. The primary safety end point was the incidence of serious adverse events through 90 days. The primary efficacy end point on a modified intent-to-treat population was a global disability end point at 90 days. Secondary end points included mortality, intracranial hemorrhage, modified Rankin scale score outcome of 0 to 2, and modified Rankin scale shift analysis. RESULTS: Between October 2005 and January 2010, 515 patients were enrolled at 68 centers in 9 countries. The primary efficacy end point did not reach statistical significance (OR, 1.17; CI, 0.81-1.67; P=0.407). The primary safety end point did not show a difference in serious adverse events (P=0.923). Ninety-day mortality was 11.3% (26/230) in treatment and 16.3% (42/257) in control (P=0.087). Post hoc analyses showed that patients presenting within 5 hours (OR, 3.33; CI, 1.31-8.48), with NIHSS score 8 to 14 (OR, 1.80; CI, 0.99-3.30), or older than age 70 years (OR, 2.02; CI, 1.02-4.03) had better modified Rankin scale score outcomes of 0 to 2; additionally, there were fewer stroke-related deaths in treatment compared to control groups (7.4% = 17/230; 14.4% = 37/257). CONCLUSIONS: The trial met its primary safety end point but not its primary efficacy end point. Signals of treatment effect were suggested on all-cause mortality, in patients presenting early, older than age 70 years, or with moderate strokes, but these require confirmation. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://clinicaltrials.gov. Unique identifier: NCT00119717

The WOVEN trial: Wingspan One-year Vascular Events and Neurologic Outcomes.

BackgroundPrior studies evaluating the Wingspan stent for treatment of symptomatic intracranial atherosclerotic disease have included patients with a spectrum of both on-label and off-label indications for the stent. The WEAVE trial assessed 152 patients stented with the Wingspan stent strictly by its current on-label indication and found a 2.6% periprocedural stroke and death rate.ObjectiveThis WOVEN study assesses the 1-year follow-up from this cohort.MethodsTwelve of the original 24 sites enrolling patients in the WEAVE trial performed follow-up chart review and imaging analysis up to 1 year after stenting. Assessment of delayed stroke and death was made in 129 patients, as well as vascular imaging follow-up to assess for in-stent re-stenosis.ResultsIn the 1-year follow-up period, seven patients had a stroke (six minor, one major). Subsequent to the periprocedural period, no deaths were recorded in the cohort. Including the four patients who had periprocedural events in the WEAVE study, there were 11 strokes or deaths of the 129 patients (8.5%) at the 1-year follow-up.ConclusionsThe WOVEN study provides the 1-year follow-up on a cohort of 129 patients who were stented according to the current on-label use. It provides a more homogeneous patient group for analysis than prior studies, and demonstrates a relatively low 8.5% 1-year stroke and death rate in stented patients

The WOVEN trial: Wingspan One-year Vascular Events and Neurologic Outcomes.

BACKGROUND: Prior studies evaluating the Wingspan stent for treatment of symptomatic intracranial atherosclerotic disease have included patients with a spectrum of both on-label and off-label indications for the stent. The WEAVE trial assessed 152 patients stented with the Wingspan stent strictly by its current on-label indication and found a 2.6% periprocedural stroke and death rate. OBJECTIVE: This WOVEN study assesses the 1-year follow-up from this cohort. METHODS: Twelve of the original 24 sites enrolling patients in the WEAVE trial performed follow-up chart review and imaging analysis up to 1 year after stenting. Assessment of delayed stroke and death was made in 129 patients, as well as vascular imaging follow-up to assess for in-stent re-stenosis. RESULTS: In the 1-year follow-up period, seven patients had a stroke (six minor, one major). Subsequent to the periprocedural period, no deaths were recorded in the cohort. Including the four patients who had periprocedural events in the WEAVE study, there were 11 strokes or deaths of the 129 patients (8.5%) at the 1-year follow-up. CONCLUSIONS: The WOVEN study provides the 1-year follow-up on a cohort of 129 patients who were stented according to the current on-label use. It provides a more homogeneous patient group for analysis than prior studies, and demonstrates a relatively low 8.5% 1-year stroke and death rate in stented patients

The WOVEN trial: Wingspan One-year Vascular Events and Neurologic Outcomes.

BackgroundPrior studies evaluating the Wingspan stent for treatment of symptomatic intracranial atherosclerotic disease have included patients with a spectrum of both on-label and off-label indications for the stent. The WEAVE trial assessed 152 patients stented with the Wingspan stent strictly by its current on-label indication and found a 2.6% periprocedural stroke and death rate.ObjectiveThis WOVEN study assesses the 1-year follow-up from this cohort.MethodsTwelve of the original 24 sites enrolling patients in the WEAVE trial performed follow-up chart review and imaging analysis up to 1 year after stenting. Assessment of delayed stroke and death was made in 129 patients, as well as vascular imaging follow-up to assess for in-stent re-stenosis.ResultsIn the 1-year follow-up period, seven patients had a stroke (six minor, one major). Subsequent to the periprocedural period, no deaths were recorded in the cohort. Including the four patients who had periprocedural events in the WEAVE study, there were 11 strokes or deaths of the 129 patients (8.5%) at the 1-year follow-up.ConclusionsThe WOVEN study provides the 1-year follow-up on a cohort of 129 patients who were stented according to the current on-label use. It provides a more homogeneous patient group for analysis than prior studies, and demonstrates a relatively low 8.5% 1-year stroke and death rate in stented patients

Impact of Thrombus Length on Outcomes After Intra-Arterial Aspiration Thrombectomy in the THERAPY Trial

Increasing thrombus length (TL) impedes recanalization after intravenous (IV) thrombolysis. We sought to determine whether the clinical benefit of aspiration thrombectomy relative to IV r-tPA (recombinant tissue-type plasminogen activator) may be greater at longer TL. THERAPY was a randomized trial of aspiration thrombectomy plus IV r-tPA versus IV r-tPA alone in large-vessel stroke patients with prospective TL measurement ≥8 mm. In this post hoc study, we evaluated the association of TL with trial end points and potential endovascular treatment effect, using univariate, multivariable, and multiplicative interaction analyses. TL data were available for all 108 patients (28% internal carotid artery, 62% M1, and 10% M2). Median TL was 14.0 mm (interquartile range, 9.7-19.5 mm). Longer TL was associated with worse outcome (90-day modified Rankin Scale score: odds ratio, 1.24 per 5-mm TL increment; 95% confidence interval, 1.04-1.52; P=0.02), even after adjusting for key outcome predictors (adjusted P=0.004). Longer TL was also associated with more serious adverse events (adjusted P=0.01), more symptomatic hemorrhages (adjusted P=0.03), and increased mortality (adjusted P=0.01). No significant relationship was observed between TL and angiographic reperfusion (modified thrombolysis in cerebral ischemia 2b-3), but greater TL was associated with longer endovascular procedural times (ρ=0.36; P=0.045). Increasing TL was associated with greater aspiration thrombectomy treatment effect (interaction term P=0.03). This might be related to a potentially stronger adverse effect of increasing TL on 90-day modified Rankin Scale for patients treated with IV r-tPA (ρ=0.39; P=0.01) compared with intra-arterial therapy (ρ=0.20; P=0.165). Ischemic stroke patients with longer symptomatic thrombi have worse 90-day clinical outcomes but may have a greater relative benefit of aspiration thrombectomy over IV r-tPA alone. URL: http://www.clinicaltrials.gov. Unique identifier: NCT0142935

Aspiration Thrombectomy After Intravenous Alteplase Versus Intravenous Alteplase Alone

BACKGROUND AND PURPOSE: Thrombectomy, primarily with stent retrievers with or without adjunctive aspiration, provided clinical benefit across multiple prospective randomized trials. Whether this benefit is exclusive to stent retrievers is unclear. METHODS: THERAPY (The Randomized, Concurrent Controlled Trial to Assess the Penumbra System\u27s Safety and Effectiveness in the Treatment of Acute Stroke; NCT01429350) was an international, multicenter, prospective, randomized (1:1), open label, blinded end point evaluation, concurrent controlled clinical trial of aspiration thrombectomy after intravenous alteplase (IAT) administration compared with intravenous-alteplase alone in patients with large vessel ischemic stroke because of a thrombus length of ≥8 mm. The primary efficacy end point was the percent of patients achieving independence at 90 days (modified Rankin Scale score, 0-2; intention-to-treat analysis). The primary safety end point was the rate of severe adverse events (SAEs) by 90 days (as treated analysis). Patients were randomized 1:1 across 36 centers in 2 countries (United States and Germany). RESULTS: Enrollment was halted after 108 (55 IAT and 53 intravenous) patients (of 692 planned) because of external evidence of the added benefit of endovascular therapy to intravenous-alteplase alone. Functional independence was achieved in 38% IAT and 30% intravenous intention-to-treat groups (P=0.52). Intention-to-treat ordinal modified Rankin Scale odds ratio was 1.76 (95% confidence interval, 0.86-3.59; P=0.12) in favor of IAT. Secondary efficacy analyses all demonstrated a consistent direction of effect toward benefit of IAT. No differences in symptomatic intracranial hemorrhage rates (9.3% IAT versus 9.7% intravenous, P=1.0) or 90-day mortality (IAT: 12% versus intravenous: 23.9%, P=0.18) were observed. CONCLUSIONS: THERAPY did not achieve its primary end point in this underpowered sample. Directions of effect for all prespecified outcomes were both internally and externally consistent toward benefit. It is possible that an alternate method of thrombectomy, primary aspiration, will benefit selected patients harboring large vessel occlusions. Further study on this topic is indicated. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01429350