Clinical trial NCT06034847: Treatment of Persistent Distal Occlusion After Successful Proximal Recanalization in Thrombectomy
Official title: Treatment of Persistent Distal Occlusion After Successful Proximal Recanalization in Thrombectomy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Stroke, Acute Thrombotic
Keywords: Large vessel occlusion
Persistent distal occlusion
Mechanical thrombectomy
Intra-arterial thrombolytics
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
First posted: 2023-09-13
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Rate of modified Rankin Scale score of 0-2. The modified Rankin score goes from 0 (no symptoms) to 6 (death). Higher scores mean a worse outcome
timeFrame: 90 days
Secondary outcomes:
measure: score on the modified Rankin Scale. The modified Rankin score goes from 0 (no symptoms) to 6 (death). Higher scores mean a worse outcome
timeFrame: 90 days
measure: Rate of functional independence
timeFrame: 90 days
measure: Change in NIHSS (National Institutes of Health Stroke Score) score. The scale goes from 0 to 42; higher scores indicated worse outcomes.
timeFrame: 24 hours
measure: Rate of NIHSS (National Institutes of Health Stroke Score) score improvement. The scale goes from 0 to 42; higher scores indicated worse outcomes.
timeFrame: 24 hours
measure: Rate of improved global ipsilateral hemispheric reperfusion
timeFrame: at end of procedure
measure: Rate of reperfusion
timeFrame: at end of procedure
measure: Rate of complete reperfusion
timeFrame: at end of procedure
measure: Procedure time
timeFrame: at end of procedure
measure: Number of thrombectomy passes
timeFrame: at end of procedure
measure: Mortality rate
timeFrame: 24 hours and 90 days
measure: Rate of procedural complications
timeFrame: at end of procedure
measure: Rate of symptomatic intracerebral hemorrhage
timeFrame: 24 hours
measure: Rate of any intracranial hemorrhage
timeFrame: 24 hours
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: CHUM - Centre Hospitalier de l'Université de Montréal
state: Quebec
Study officials:
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
name: Daniela Iancu, MD
role: PRINCIPAL_INVESTIGATOR
References: