Treatment of Persistent Distal Occlusion After Successful Proximal Recanalization in Thrombectomy

NCT ID: NCT06034847

Last Updated: 2024-08-15

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-30
• Study Completion Date: 2029-01-31

Brief Summary

In stroke patients, mechanical thrombectomy is now the standard of care when the stroke is due to large proximal cerebral vessel occlusion. The purpose of the 2BE3 trial is to test whether adjunct rescue treatment of persisting distal occlusions after successful proximal recanalization of the large vessel occlusion can be proposed as an additional intervention to restore reperfusion of affected stroke tissue and improve clinical outcomes.

The rescue therapies will be either mechanical (small stent retrievers and/or small aspiration catheters) or pharmacological (infusion of intra-arterial thrombolytics).

Patients will be randomized to conservative management (mechanical thrombectomy with or without IV thrombolytics of large proximal vessels) or rescue therapy (mechanical or pharmacological interventions in distal vessels in addition to conservative management). Each patient will be followed for 3 months post-intervention.

The data collected will be clinical assessments and angiographic imaging to evaluate the reperfusion state.

Detailed Description

The purpose of the 2BE3 trial is to provide a clinical trial context for the use of rescue therapy (mechanical or pharmacological therapies) in patients with persistent distal occlusions after treatment of large vessel occlusions with mechanical thrombectomy and IV thrombolytics. The main hypothesis is that rescue therapy with mechanical or pharmacological therapies, compared with conservative management would result in improved clinical and reperfusion scores at 90 days.

The extent of reperfusion is an interesting therapeutic target because reperfusion status is a strong indicator of clinical outcome: grades of better reperfusion are incrementally associated with better clinical outcomes. Despite increased expertise of neuro-interventional teams and the evolution in thrombectomy devices, incomplete reperfusion occurs in almost half of patients undergoing treatment of large vessel occlusions. Thus, complementary treatments targeting distal occlusions and known as "rescue therapy" have been introduced to reach complete or near complete reperfusion.

The devices and techniques proposed as rescue therapies include small stent retrievers, small aspiration catheters and intra-arterial thrombolytics. Case studies and registries have shown high reperfusion rates and low rates of periprocedural complications; however, there is lack of randomized data to show the impact of rescue therapies on patient outcomes and safety compared to conservative management (treatment of large vessel occlusions only). A randomized clinical trial is therefore needed.

The 2BE3 trial is a simple randomized trial designed to be integrated into daily clinical practice. It will address whether rescue therapies truly offer a safe and more effective alternative to conservative management. Selection criteria are loose in order to be of use to most patients. Endpoints are simple, clinical, meaningful, valuable and resistant to bias. It includes no extra risk or cost of visits beyond what is required in routine care.

The design is multicenter, prospective, randomized, controlled, open-label study with blinded evaluation (PROBE design). The study population is acute ischemic stroke patients with persistent distal occlusions after treatment of large vessel occlusion with mechanical thrombectomy and/or intravenous thrombolysis. The total number of patients will be 300, 150 in each arm, each followed for 3 months post-intervention.

Conditions

Stroke, Acute Thrombotic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Conservative management

Mechanical thrombectomy of large vessel occlusions with or without administration of IV thrombolytics

Group Type: ACTIVE_COMPARATOR

Mechanical thrombectomy in proximal large vessels

Intervention Type: DEVICE

mechanical thrombectomy with retrievable stents to remove clots in proximal large vessels, combined or not with distal aspiration, combined or not with IV thrombolytics

Rescue therapy

In addition to conservative management, rescue therapy in distal occlusions consisting of either mechanical thrombectomy with small stent retrievers with or without contact aspiration, or intra-arterial pharmacotherapy with tPA (tissue Plasminogen Activator), uPA (urokinase Plasminogen Activator) or tenecteplase.

Group Type: ACTIVE_COMPARATOR

Mechanical thrombectomy in proximal large vessels

Intervention Type: DEVICE

mechanical thrombectomy with retrievable stents to remove clots in proximal large vessels, combined or not with distal aspiration, combined or not with IV thrombolytics

Rescue mechanical thrombectomy in distal vessels

Intervention Type: DEVICE

In addition to mechanical thrombectomy in proximal large vessels, mechanical thrombectomy in distal vessels with small stent retrievers combined or not with contact aspiration, or intra-arterial perfusion of thrombolytics such as tPA or uPA or tenecpeplase

Interventions

Mechanical thrombectomy in proximal large vessels

mechanical thrombectomy with retrievable stents to remove clots in proximal large vessels, combined or not with distal aspiration, combined or not with IV thrombolytics

Intervention Type: DEVICE

Rescue mechanical thrombectomy in distal vessels

In addition to mechanical thrombectomy in proximal large vessels, mechanical thrombectomy in distal vessels with small stent retrievers combined or not with contact aspiration, or intra-arterial perfusion of thrombolytics such as tPA or uPA or tenecpeplase

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• any patient with a large vessel occlusion in the M1 or M2 segment of the MCA (Middle Cerebral Artery), supraclinoid ICA (Internal Carotid Artery), or basilar artery who is a candidate for thrombectomy
• with a persistent distal occlusion in M2-M4, A1-A5, P1-P5 after successful recanalization of the proximal clot with mechanical thrombectomy and/or IV thrombolysis

Exclusion Criteria

• poor 3 month prognosis from comorbidities
• evidence of active bleeding on examination
• recent surgery with a significant risk of bleeding
• VKA (Vitamin K Antagonists) oral anticoagulation with INR (International Normalized Ratio) - > 1.7
• curative heparin or direct oral anticoagulants in previous 48 hours
• platelet count < 100 000/mm3

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre hospitalier de l'Université de Montréal (CHUM)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniela Iancu, MD

Role: PRINCIPAL_INVESTIGATOR

Centre hospitalier de l'Université de Montréal (CHUM)

Locations

CHUM - Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, Canada

Countries

Canada

Central Contacts

Daniela Iancu, MD

Role: CONTACT

daniela.iancu.med@ssss.gouv.qc.ca

15148908000 ext. 8450

Guylaine Gevry, BSc

Role: CONTACT

guylaine.gevry.chum@ssss.gouv.qc.ca

15148908000 ext. 27235

Facility Contacts

Guylaine Gevry, BSc

Role: primary

guylaine.gevry.chum@ssss.gouv.qc.ca

15148908000 ext. 27235

Other Identifiers

2024-11741

Identifier Type: -

Identifier Source: org_study_id