Endovascular Thrombectomy for Stroke

(OUTER LIMITS Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must not be taking: tPA, TNK

Disqualifiers: Pregnant, Advanced illness, Severe hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 hours from stroke onset

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial investigators for guidance.

What data supports the effectiveness of the treatment Endovascular Thrombectomy for Stroke?

Research shows that endovascular thrombectomy is effective for treating certain types of strokes, improving outcomes like disability-free survival and quality of life. It has proven benefits when performed within 24 hours of stroke symptoms, and some cases suggest it may work even beyond this timeframe. ^{1 2 3 4 5}

Is endovascular thrombectomy generally safe for humans?

There is limited information on the safety of endovascular thrombectomy, especially regarding complications during the procedure and its use in different populations, such as children and those on certain blood thinners. ^{6 7 8 9 10}

How is endovascular thrombectomy different from other stroke treatments?

Endovascular thrombectomy is unique because it involves physically removing a blood clot from a blocked artery in the brain using specialized devices, which is different from traditional treatments that typically use medication to dissolve clots. This method has been shown to be effective even in large-volume ischemic strokes, expanding its use beyond smaller strokes. ^{8 11 12 13 14}

What is the purpose of this trial?

The purpose of this study is to assess the safety and efficacy of endovascular thrombectomy in both an early and extended time window in patients with large strokes due to large artery occlusion.

Research Team

Gregory Albers, MD

Principal Investigator

Stanford University

Jeremy Heit, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for patients who have had a large stroke caused by a blockage in a big artery. It's looking at how well they respond to clot removal procedures done within different time frames after their stroke.

Inclusion Criteria

Patient/ Legally Authorized Representative has signed the Informed Consent form.

I show signs of a recent stroke affecting the front part of my brain.

My stroke severity score is 10 or higher.

Exclusion Criteria

Pregnant

Unable to undergo a contrast brain perfusion scan with either MRI or CT

Baseline blood glucose of <50mg/dL (2.78 mmol) or >400mg/dL (22.20 mmol)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either endovascular therapy plus medical therapy or medical therapy alone based on randomization

Up to 24 hours from stroke onset

In-hospital treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Regular follow-up visits

Treatment Details

Interventions

• Endovascular Thrombectomy

Trial Overview The study tests the safety and effectiveness of endovascular thrombectomy, which is a procedure to remove blood clots from arteries using FDA-approved devices, performed at varying times post-stroke.

Participant Groups

Group I: Endovascular Thrombectomy Experimental Treatment 2 Interventions

Treatment with one or more thrombectomy devices (only the devices listed in the study protocol are approved for use) plus standard medical therapy for patients with acute ischemic anterior circulation strokes due to large artery occlusion who present with an eligible large ischemic core lesion, and who can be treated within 24 hours of stroke onset.

Group II: Medical Management Active Control 1 Intervention

Standard medical therapy, based on current AHA guidelines

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Findings from Research

In a 5-year study of 66 patients undergoing endovascular thrombectomy for acute ischemic stroke, 53% achieved a favorable outcome (mRS 0-2) at 90 days, indicating the procedure's effectiveness in real-world settings.

Successful recanalization was achieved in 68% of cases, and higher scores on the Alberta Stroke Program Early CT Score (ASPECTS) and the thrombolysis in cerebral infarction (TICI) grading system were independently associated with better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome Evaluation of Acute Ischemic Stroke Patients Treated with Endovascular Thrombectomy: A Single-Institution Experience in the Era of Randomized Controlled Trials. Sarzetto, F., Gupta, S., Alotaibi, NM., et al.[2017]

Endovascular thrombectomy is an effective treatment for patients with symptomatic intracranial large-vessel occlusion, showing benefits even up to 24 hours after symptom onset for those who were functionally independent before the stroke.

This case report suggests that thrombectomy may also be beneficial beyond the 24-hour window, as demonstrated in a young woman who received the intervention after this timeframe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endovascular thrombectomy: 31 hours from symptom onset. Beharry, J., Duncan, R., Krauss, M., et al.[2020]

In a study of 21 pediatric patients undergoing endovascular thrombectomy for acute ischemic stroke, 83% achieved successful recanalization, indicating the procedure's efficacy in treating large-vessel occlusions in children.

Significant clinical improvements were observed, with a mean reduction in the Pediatric National Institutes of Health Stroke Scale score from 13 at presentation to 2 at discharge, and 86% of patients had favorable outcomes (mRS score of 0 to 2) by 90 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endovascular Thrombectomy for Pediatric Acute Ischemic Stroke: A Multi-Institutional Experience of Technical and Clinical Outcomes. Ravindra, VM., Alexander, M., Taussky, P., et al.[2021]

In a study of 1917 patients who underwent thrombectomy, only 11% were treated within 6-24 hours, and those who were trial-ineligible had similar rates of good outcomes (27%) compared to trial-eligible patients (20%), indicating that eligibility criteria may not significantly impact clinical outcomes in real-world settings.

Patients with large CT perfusion imaging lesions who were trial-ineligible experienced more hemorrhagic complications (33%) and worse outcomes, suggesting that careful patient selection is crucial to minimize risks during late thrombectomy procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late Thrombectomy in Clinical Practice : Retrospective Application of DAWN/DEFUSE3 Criteria within the German Stroke Registry. Herzberg, M., Scherling, K., Stahl, R., et al.[2023]

In a study of 70 patients with large vessel occlusion ischemic stroke, those who underwent endovascular thrombectomy after alteplase treatment showed significantly better disability-weighted utility scores and longer life expectancy compared to those who received alteplase only.

Patients in the thrombectomy group experienced shorter hospital stays and lower overall acute care costs, saving an average of $4,365 per patient while also gaining more quality-adjusted life years (QALYs) and experiencing improved long-term survival and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost. Campbell, BCV., Mitchell, PJ., Churilov, L., et al.[2022]

In a study of 94 patients with mild stroke syndromes and distal vessel occlusions, endovascular thrombectomy (EVT) showed similar rates of excellent and good outcomes compared to intravenous thrombolysis (IVT), with 75% and 70% achieving excellent outcomes respectively.

However, EVT was associated with a higher risk of intracranial bleeding (13.3% vs. 1.6% for IVT) and significantly higher mortality (13.3% vs. 1.6%), suggesting that while EVT can be effective, it carries increased safety risks that must be carefully considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distal arterial occlusions in patients with mild strokes - is endovascular therapy superior to thrombolysis alone? Nagel, S., Pfaff, J., Herweh, C., et al.[2020]

In a study of 28 patients with ischemic stroke undergoing endovascular thrombectomy, the procedure appeared to be safe for those on non-vitamin K antagonist oral anticoagulants, with only 1 patient experiencing symptomatic intracranial hemorrhage despite a 46% rate of any intracranial hemorrhage.

Successful reperfusion was achieved in 59% of cases, and at 3 months, 19% of patients had a favorable functional outcome, indicating that thrombectomy can be effective in this patient population, although further research with larger cohorts is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Endovascular Thrombectomy in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulants. Purrucker, JC., Wolf, M., Haas, K., et al.[2022]

Endovascular thrombectomy significantly improved functional outcomes in patients with large ischemic strokes compared to medical care alone, with a generalized odds ratio of 1.51 indicating better recovery at 90 days.

While thrombectomy was effective, it was associated with some vascular complications, including arterial access-site issues and vessel perforations, but the rates of symptomatic intracranial hemorrhage were low in both treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial of Endovascular Thrombectomy for Large Ischemic Strokes. Sarraj, A., Hassan, AE., Abraham, MG., et al.[2023]

Endovascular thrombectomy in children with acute ischemic stroke due to large-vessel occlusion shows high efficacy, with 88.5% achieving successful recanalization and a significant reduction in stroke severity (mean NIH Stroke Scale score reduction of 7.37).

Children experienced better outcomes compared to adults, including higher rates of good neurological recovery (76.1% vs. 46.0%), fewer major complications (3.6% vs. 30.4%), and lower mortality rates (1.0% vs. 12.9%), suggesting that this treatment is both safe and effective for pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How do children fare compared with adults? Comparing relative outcomes after thrombectomy for acute ischemic stroke due to large-vessel occlusion. Findlay, MC., Grandhi, R., Nelson, JR., et al.[2023]

In a study of 4799 patients undergoing endovascular thrombectomy for large vessel occlusion strokes, the cumulative incidence of complications was found to be 201 per 1000 patients, with significant associations between ongoing antiplatelet therapy and specific occlusion sites leading to higher risks of subarachnoid hemorrhage and arterial perforation.

Complications such as symptomatic intracerebral hemorrhage and subarachnoid hemorrhage were linked to worse functional outcomes and increased mortality at three months, highlighting the importance of identifying risk factors to improve patient management and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of mechanical thrombectomy for acute ischemic stroke: Incidence, risk factors, and clinical relevance in the Italian Registry of Endovascular Treatment in acute stroke. Salsano, G., Pracucci, G., Mavilio, N., et al.[2022]

Endovascular stroke therapy has significantly improved the treatment of acute ischemic stroke over the past decade, leading to better patient outcomes.

The article discusses the scientific basis and evidence supporting endovascular revascularization, along with technical details and case examples of various thrombectomy methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endovascular treatment of acute ischemic stroke. Natarajan, SK., Eller, JL., Snyder, KV., et al.[2013]

Endovascular thrombectomy significantly improves functional outcomes in patients with large-volume ischemic strokes compared to medical management, based on a meta-analysis of three randomized trials involving 1011 participants.

While there is a trend toward a higher risk of symptomatic intracranial hemorrhage in the thrombectomy group, the overall risk of significant complications does not exceed that of medical management, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endovascular Thrombectomy for the Treatment of Large Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Control Trials. Atchley, TJ., Estevez-Ordonez, D., Laskay, NMB., et al.[2023]

A total of 196 clinical trials on endovascular thrombectomy for ischemic stroke were identified, with 82.1% initiated in the last 5 years, indicating a rapid increase in research activity in this area.

Most trials focused on the safety and efficacy of thrombectomy devices and procedural aspects, with a significant number funded by academic centers, highlighting the collaborative effort in advancing stroke treatment technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trials in thrombectomy for acute ischemic stroke: Describing the state of clinical research in the field. Martini, ML., Neifert, SN., Lara-Reyna, JJ., et al.[2021]

In a review of 5 patients who underwent endovascular thrombectomy using the MERCI and Penumbra devices, all patients achieved partial recanalization, but they also exhibited extensive cerebral infarcts and complications such as hemorrhagic transformations after the procedure.

The study highlighted that complicated atherosclerosis was a common finding in the patients' basal arteries, suggesting that pre-existing vascular conditions may have contributed to the severity of their strokes and subsequent outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autopsy findings after intracranial thrombectomy for acute ischemic stroke: a clinicopathologic study of 5 patients. Yin, NS., Benavides, S., Starkman, S., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Outcome Evaluation of Acute Ischemic Stroke Patients Treated with Endovascular Thrombectomy: A Single-Institution Experience in the Era of Randomized Controlled Trials. [2017]

2. England pubmed.ncbi.nlm.nih.gov

Endovascular thrombectomy: 31 hours from symptom onset. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Endovascular Thrombectomy for Pediatric Acute Ischemic Stroke: A Multi-Institutional Experience of Technical and Clinical Outcomes. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Late Thrombectomy in Clinical Practice : Retrospective Application of DAWN/DEFUSE3 Criteria within the German Stroke Registry. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Distal arterial occlusions in patients with mild strokes - is endovascular therapy superior to thrombolysis alone? [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Safety of Endovascular Thrombectomy in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulants. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Trial of Endovascular Thrombectomy for Large Ischemic Strokes. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

How do children fare compared with adults? Comparing relative outcomes after thrombectomy for acute ischemic stroke due to large-vessel occlusion. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Complications of mechanical thrombectomy for acute ischemic stroke: Incidence, risk factors, and clinical relevance in the Italian Registry of Endovascular Treatment in acute stroke. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Endovascular treatment of acute ischemic stroke. [2013]

12. United States pubmed.ncbi.nlm.nih.gov

Endovascular Thrombectomy for the Treatment of Large Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Control Trials. [2023]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Trials in thrombectomy for acute ischemic stroke: Describing the state of clinical research in the field. [2021]

14. United States pubmed.ncbi.nlm.nih.gov

Autopsy findings after intracranial thrombectomy for acute ischemic stroke: a clinicopathologic study of 5 patients. [2021]