Thrombectomy + Angioplasty/Stenting for Stroke

(PICASSO Trial)

Recruiting at 54 trial locations

Overseen By Nickalus R. Khan, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Mercy Health Ohio

Must not be taking: Anticoagulants

Disqualifiers: Pregnancy, Refractory hypertension, Intracranial tumors, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Immediate intervention

404 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is studying two methods to treat strokes caused by blocked blood vessels in the brain. One group will receive a treatment that uses a small device to remove the blockage and then places a tiny tube (stent) to keep the artery open. The other group will have the blockage removed and the artery widened without using the stent. Individuals who have recently experienced a stroke with a blocked artery in the head and another blockage in the neck might be suitable for this trial, especially if they haven't responded to the usual clot-busting drugs. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot participate if you have a contraindication (reason not to use) to antiplatelet or thrombolytic therapy, or if you are on anticoagulant therapy with certain blood test results.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that mechanical thrombectomy (MT) effectively and safely treats sudden strokes caused by blocked blood flow. Many studies have found that this treatment can help stroke patients recover better without causing major harm.

For acute carotid stenting (ACS), research indicates it is generally safe, with a low chance of serious problems. Specifically, one study found very few cases of severe issues like death or additional strokes.

These findings suggest that the treatments in this trial—whether using MT alone or with ACS—are safe for people, based on previous research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer new ways to tackle strokes caused by blockages in the carotid artery. Unlike standard treatments, which usually involve intravenous medication or surgery, these options combine intra-arterial therapy with mechanical thrombectomy. One arm of the trial explores adding acute carotid stenting, which could improve blood flow by keeping the artery open longer. The other arm uses a combination of mechanical thrombectomy and angioplasty or aspiration without stenting, potentially offering a less invasive option. These treatments aim to restore brain blood flow more effectively and quickly, which could lead to better recovery outcomes for stroke patients.

What evidence suggests that this trial's treatments could be effective for acute ischemic stroke?

Research shows that mechanical thrombectomy (MT), one of the treatments in this trial, effectively treats sudden strokes caused by blocked blood flow to the brain. Studies have found that MT reduces disability compared to medication alone and improves long-term recovery, especially for strokes from large artery blockages. In this trial, some participants will receive MT combined with acute carotid stenting (CAS). Research suggests that CAS works well when combined with a minimally invasive procedure using thin tubes called catheters. Patients who undergo CAS during stroke treatment tend to recover better and have a higher chance of reopening blocked arteries. Both MT and CAS, as studied in this trial, show promise in improving stroke recovery. ^{1 2 3 5 6}

Who Is on the Research Team?

Osama Zaidat, MD

Principal Investigator

Mercy Health St. Vincent Medical Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-85 who've had a stroke within the last 24 hours due to a blockage in the arteries of the brain and neck. They should have moderate to severe symptoms but still be relatively independent before the stroke, with no major health issues that would interfere with treatment or reduce life expectancy below one year.

Inclusion Criteria

I was mostly independent before my stroke.

I am experiencing symptoms similar to a minor stroke.

Ability to obtain signed informed consent

Exclusion Criteria

I have a brain tumor, but it's not a meningioma needing surgery within a year.

I am not pregnant or have a negative pregnancy test if of child-bearing age.

You have certain brain conditions visible on a CT scan, such as shifting of the midline, bleeding in the brain, or pressure on the ventricles.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intra-arterial mechanical thrombectomy with or without acute carotid stenting

Immediate intervention

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Remote assessment of NIHSS, mRS scale may be provided

Long-term Follow-up

Participants are assessed for primary outcomes at one year post-randomization

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Antiplatelet Drug
• EMBOGUARD Balloon Guide Catheter
• Intra-arterial Therapy

Trial Overview

The study tests if removing clots from brain arteries (mechanical thrombectomy) combined with immediate stenting of blocked neck arteries is better than clot removal alone. Patients are randomly assigned to either get a stent plus antiplatelet drugs by mouth or IV, or just standard care after clot removal.

How Is the Trial Designed?

Group I: MT+CAT Experimental Treatment 1 Intervention

Non-stenting group constitutes best medical management (BMM)+intra-arterial treatment (IAT) with mechanical thrombectomy (for IVO) added to extra-cranial proximal carotid occlusion angioplasty or aspiration (MT+CAT)

Group II: MT+CAS Experimental Treatment 2 Interventions

Acute carotid stenting (ACS) approach constitutes BMM+IAT with acute carotid stenting (ACS) of the extracranial proximal carotid artery, spanning the cervical internal carotid artery (ICA), ICA origin, and the distal common carotid artery (CCA, across the bifurcation) as in the example of left (L) carotid stenting figure below (MT+CAS). Within the stenting arm, there will be 2 different subgroups based on the antiplatelet treatment protocol per the site standard of care (oral antiplatelet or IV antiplatelet medication (e.g., Cangrelor or others).

Intra-arterial Therapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Mechanical Thrombectomy for:

• Acute ischemic stroke due to large vessel occlusion

Approved in United States as Mechanical Thrombectomy for:

• Acute ischemic stroke due to large vessel occlusion

Approved in Canada as Mechanical Thrombectomy for:

• Acute ischemic stroke due to large vessel occlusion

Who Is Running the Clinical Trial?

Mercy Health Ohio

Lead Sponsor

Trials

15

Recruited

1,600+

Published Research Related to This Trial

Emergency microsurgical embolectomy can be an effective alternative treatment for restoring blood flow in patients with acute ischemic stroke due to major artery occlusion, especially when thrombolytic therapy is contraindicated or has failed.

The case report highlights two specific instances where this technique was successfully used for occlusions in the middle cerebral artery and internal carotid artery, suggesting its potential as a viable option in critical situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emergency microsurgical embolectomy for the treatment of acute intracranial artery occlusion: report of two cases. Kim, DW., Jang, SJ., Kang, SD.[2021]

Intra-arterial thrombolysis (IAT) combined with mechanical thrombectomy (MT) showed a trend towards improved functional independence in stroke patients, but the results were not statistically significant across 18 studies involving 7572 patients.

IAT was associated with significantly higher odds of achieving near-complete or complete angiographic recanalization, suggesting it may enhance the effectiveness of MT in restoring blood flow during acute stroke treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanical thrombectomy with intra-arterial thrombolysis versus mechanical thrombectomy alone in patients with acute ischemic stroke: A systematic review and meta-analysis. Qureshi, AI., Lodhi, A., Akhtar, IN., et al.[2023]

Endovascular treatments, such as intra-arterial thrombolysis and mechanical thrombectomy, are critical for managing acute ischemic stroke, especially for patients who do not respond to intravenous thrombolysis or are beyond the treatment window.

The cases discussed highlight the importance of rapid diagnosis and interdisciplinary collaboration in stroke management, emphasizing that patients with symptomatic intracranial stenosis should be considered for angioplasty and stenting as part of their treatment plan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Stroke--endovascular treatment methods]. Jacobsen, EA.[2016]

Intra-arterial thrombectomy is a highly effective treatment for acute ischemic stroke, particularly for patients with documented occlusions in specific arteries and severe neurological deficits, provided the procedure is performed within 6 hours of symptom onset.

The combination of intra-arterial thrombectomy with prior administration of r-tPA enhances patient outcomes, and it is crucial that r-tPA is not withheld if the patient meets the criteria for its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stroke Neurologist's Perspective on the New Endovascular Trials. Grotta, JC., Hacke, W.[2022]

Intra-arterial thrombolysis is a promising treatment for acute thromboembolic stroke, offering a longer treatment window and improved outcomes compared to intravenous t-PA.

Successful outcomes from intra-arterial thrombolysis depend on careful patient selection to minimize the risk of intracranial hemorrhage, emphasizing the importance of evaluating specific patient features before treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-arterial thrombolysis for acute ischemic stroke. Burnette, WC., Nesbit, GM.[2020]

From 2010 to 2016, the use of mechanical thrombectomy (MT) for treating ischemic strokes in Germany increased significantly from 0.8% to 4.7%, particularly after the publication of key randomized trials, indicating its growing acceptance as an effective treatment option.

Despite the overall increase in MT procedures, there remains a notable disparity in treatment rates between urban and rural areas, with rural patients receiving MT at significantly lower rates (3.8% vs 5.4% in urban areas) in 2016.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distribution and evolution of acute interventional ischemic stroke treatment in Germany from 2010 to 2016. Weber, R., Eyding, J., Kitzrow, M., et al.[2022]

In a study of 512 patients with acute anterior circulation tandem lesions, combining intravenous thrombolysis (IVT) with mechanical thrombectomy (MT) did not increase the risk of symptomatic intracranial hemorrhage (sICH) or other serious complications compared to MT alone.

Patients receiving IVT+MT had a higher likelihood of achieving favorable functional outcomes at 90 days, indicating that this combination treatment can be effective without compromising safety, although caution is advised when using intraprocedural antiplatelet therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Outcomes of Mechanical Thrombectomy Versus Combined Thrombectomy and Intravenous Thrombolysis in Tandem Lesions. Rodriguez-Calienes, A., Galecio-Castillo, M., Farooqui, M., et al.[2023]

Mechanical thrombectomy using stent retrievers has the highest recanalization rates for treating acute strokes, making it a leading technique in this field.

Recent clinical trials show that mechanical thrombectomy significantly improves patient outcomes compared to intravenous rTPA alone for acute occlusions in the anterior circulation of the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Mechanical thrombectomy - technique]. Yilmaz, U., Mühl-Benninghaus, R., Reith, W.[2018]

In a study of 305 patients, those who failed intravenous tissue plasminogen activator (IV tPA) treatment showed a higher revascularization rate (73%) and lower mortality (27.7%) compared to those treated with IV tPA alone (63% revascularization and 40.1% mortality).

Mechanical thrombectomy after failed IV tPA resulted in similar rates of good clinical outcomes and procedural complications compared to thrombectomy in patients who were not eligible for IV tPA, indicating that thrombectomy is a viable option regardless of prior IV tPA treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endovascular thrombectomy for acute ischemic stroke in failed intravenous tissue plasminogen activator versus non-intravenous tissue plasminogen activator patients: revascularization and outcomes stratified by the site of arterial occlusions. Shi, ZS., Loh, Y., Walker, G., et al.[2022]

Intra-arterial thrombolysis showed a modest benefit over standard treatment for ischemic stroke patients, reducing the risk of poor functional outcomes, but did not demonstrate a clear advantage over intravenous thrombolysis.

While intra-arterial thrombolysis did not increase mortality rates, it was associated with a significantly higher risk of symptomatic intracranial hemorrhage, nearly four times more likely than standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-arterial thrombolysis vs. standard treatment or intravenous thrombolysis in adults with acute ischemic stroke: a systematic review and meta-analysis. Nam, J., Jing, H., O'Reilly, D.[2018]

In a study of 205 acute ischemic stroke patients with tandem occlusion, those who received prior intravenous thrombolysis (IVT) showed no increased risk of symptomatic intracerebral hemorrhage when treated with emergent carotid artery stenting and mechanical thrombectomy.

Patients who received IVT had a significantly lower 90-day all-cause mortality rate (8% vs. 20%) compared to those who did not receive IVT, suggesting that prior IVT may improve overall outcomes without increasing hemorrhagic complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emergent Carotid Stenting Plus Thrombectomy After Thrombolysis in Tandem Strokes: Analysis of the TITAN Registry. Anadani, M., Spiotta, AM., Alawieh, A., et al.[2020]

In a study of 311 patients with large-vessel occlusion ischemic stroke, the use of intra-arterial fibrinolytics (either tPA or urokinase) as an adjunct to mechanical thrombectomy showed a potential for improving reperfusion rates, with 50.9% of patients experiencing angiographic improvement.

However, there was an 8.8% occurrence of symptomatic intracranial hemorrhage (sICH), particularly in patients with lower initial TICI scores or internal carotid artery occlusions, highlighting the need for careful patient selection when considering this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Angiographic Efficacy of Intra-Arterial Fibrinolytics as Adjunct to Mechanical Thrombectomy: Results from the INFINITY Registry. Kaesmacher, J., Abdullayev, N., Maamari, B., et al.[2021]

In a study of 16 patients undergoing intra-arterial thrombolysis for acute ischemic stroke, a high recanalization rate of 69% was achieved, indicating the treatment's efficacy in restoring blood flow.

The treatment resulted in a favorable outcome for 46% of patients, suggesting that intra-arterial therapy can be beneficial, especially for those with severe neurological injury and specific occlusion types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Endovascular treatment and intra-arterial thrombolysis in acute ischemic stroke]. Escudero, D., Molina, R., Viña, L., et al.[2016]

In a study of 326 patients with acute large vessel occlusion, rescue angioplasty and/or stenting significantly improved functional independence at 90 days compared to mechanical thrombectomy (MT) alone, with 44.2% of patients in the rescue group achieving independence versus 29.5% in the MT group.

For patients who experienced failed MT, the rescue therapy showed even greater benefits, with 39.0% achieving functional independence compared to only 17.0% in the MT alone group, indicating that rescue therapy is particularly effective in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rescue angioplasty and/or stenting after mechanical thrombectomy: who can benefit? Jia, B., Zhang, L., Pan, Y., et al.[2023]

Citations

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Carotid Artery Stenting during Endovascular treatment of ...

This study will provide high-quality randomized data on the efficacy and safety of immediate CAS in patients undergoing EVT for acute ischemic stroke due to a ...

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ahajournals.org

ahajournals.org/doi/10.1161/SVIN.124.001459

Carotid Artery Stenting Outcomes by Neurointerventional ...

The primary outcomes occurred in 26 (1.8%) cases, with 13 (0.9%) death, 8 (0.55%) symptomatic ischemic stroke, 4 (0.28%) symptomatic ...

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jamanetwork.com

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Functional and Safety Outcomes of Carotid Artery Stenting ...

This cross-sectional study evaluates the clinical and technical outcomes of carotid artery stenting vs no stenting during mechanical ...

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neurology.org

neurology.org/doi/10.1212/WNL.0000000000214067

Emergent Carotid Artery Stenting in Patients With Acute ...

In addition to better functional outcome, patients who underwent eCAS showed a 4-time fold increased probability of successful recanalization after EVT, which ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S2666688X23000941

Immediate Carotid Artery Stenting or Deferred Treatment in ...

This would negate the need for a second procedure, immediately reduce the risk of stroke recurrence, increase patient satisfaction, and could be cost effective.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10881598/

Efficacy and Safety Outcomes for Acute Ischemic Stroke ...

A single antiplatelet therapy with tirofiban regardless of premedication may improve the functional outcome in patients with stroke.