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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the safety and effectiveness of endovascular thrombectomy, a procedure that removes blood clots from blocked arteries, for individuals who have experienced large strokes due to blocked arteries. The study will compare this treatment to standard medical care to determine if it is more effective, particularly when administered within 24 hours of the stroke. This trial may suit those who have suffered a sudden, severe stroke impacting daily activities and can begin treatment within a day of the stroke. As an unphased trial, it offers participants the chance to contribute to significant research that could enhance stroke treatment options.

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 prior data suggests that endovascular thrombectomy is safe for stroke patients?

Research has shown that endovascular thrombectomy is generally safe for treating large strokes. One study found that patients treated within 6 to 24 hours experienced similar safety outcomes to those treated sooner, suggesting the procedure is well-tolerated over a longer period. Another study demonstrated that the procedure is safe and effective for patients with large areas of brain damage due to lack of blood flow, even after 90 days. Although some patients may experience complications, the overall safety record remains reassuring. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Endovascular thrombectomy is unique because it physically removes clots from blocked arteries in the brain, providing a direct approach to treat acute ischemic strokes. Unlike standard medical therapy, which often relies on medications like tissue plasminogen activator (tPA) to dissolve clots, thrombectomy uses specialized devices to extract the blockage, potentially leading to faster restoration of blood flow. Researchers are excited because this method can be effective even when initiated up to 24 hours after stroke onset, offering a wider treatment window than current medication-based approaches.

What evidence suggests that endovascular thrombectomy is effective for large strokes?

Research has shown that endovascular thrombectomy, a procedure available to participants in this trial, can help treat large strokes caused by blocked arteries. Studies have found this procedure more effective at reducing disability than medication alone. Patients who undergo this treatment often experience better recovery outcomes 90 days after their stroke. However, some research indicates it doesn't always lead to significantly better results for everyone. Additionally, some studies report higher rates of death and complications during hospitalization, highlighting the associated risks. ^{2 4 5 6 7}

Who Is on the Research Team?

Gregory Albers, MD

Principal Investigator

Stanford University

Jeremy Heit, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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 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]

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]

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 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]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2214403

Trial of Endovascular Thrombectomy for Large Ischemic ... Endovascular thrombectomy has been shown to be more effective in reducing disability than medical therapy alone in selected patients with ischemic stroke.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12578045/

Long-term efficacy and safety of endovascular thrombectomy ... Endovascular thrombectomy (EVT) improves functional outcomes at 90 days in patients with acute ischemic stroke (AIS) with large vessel occlusion ...

3. strokejournal.org strokejournal.org/article/S1052-3057(24)00651-7/fulltext

Endovascular thrombectomy for acute ischemic stroke with ... Anterior cerebral artery (ACA) occlusions account for up to 4 % of all acute ischemic strokes and may lead to debilitating outcomes.

4. neurology.org neurology.org/doi/10.1212/WNL.0000000000214015

Endovascular Treatment in Acute Ischemic Stroke Due to ... The present meta-analysis demonstrates that EVT does not significantly improve excellent or good functional outcomes at 3 months compared with ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002962925010687

Endovascular therapy in acute ischemic stroke: A six-year ... Despite increased use of EVT, our study revealed that patients undergoing this intervention experienced higher in-hospital mortality and complication rates.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10574302/

Clinical and Safety Outcomes of Endovascular Therapy 6 ... EVT for acute TL-LVO treated within 6–24 hours after LKW was associated with similar rates of clinical and safety outcomes, compared to patients treated within ...

7. thelancet.com thelancet.com/journals/laneur/article/PIIS1474-4422(24)00278-3/fulltext

Endovascular thrombectomy for acute ischaemic stroke ... The TENSION trial showed the safety and efficacy of endovascular thrombectomy in patients with ischaemic stroke and large infarct at 90 days. We ...