Acute Ischemic Stroke
Conditions
Keywords
thrombectomy, endovascular treatment, distal occlusion
Brief summary
The goal of this clinical trial is to determine whether rescue distal mechanical thrombectomy can improve outcomes in patients with persistent distal occlusions after successful proximal mechanical thrombectomy for acute ischemic stroke. Many patients with acute ischemic stroke caused by large vessel occlusion undergo emergency treatment with proximal mechanical thrombectomy, which removes the main clot and restores flow in a large artery. However, in some patients, one or more smaller distal arteries remain occluded after successful proximal recanalization. It is not yet known whether treating these persistent distal occlusions improves angiographic or clinical outcomes. This study will compare two approaches: Rescue distal mechanical thrombectomy: an additional distal mechanical thrombectomy procedure is performed during the same endovascular session. Conservative management: no additional distal endovascular intervention is performed after successful proximal mechanical thrombectomy. The main questions the study aims to answer are: * Is rescue distal mechanical thrombectomy feasible in this setting? * Is it safe? * Does it improve angiographic and clinical outcomes? Participants will be randomly assigned during the index endovascular procedure to one of the two study groups and will be followed with imaging and clinical assessments during hospitalization and at 90 days. Approximately 72 participants will take part in this study at the Centre hospitalier de l'Université de Montréal (CHUM).
Detailed description
The 2BE3 - Phase II study is a clinical trial designed to evaluate the feasibility and safety of rescue distal mechanical thrombectomy in patients with persistent distal occlusions following successful proximal recanalization. Endovascular thrombectomy has become the standard of care for acute ischemic stroke caused by large vessel occlusion (LVO), with substantial improvement in clinical outcomes demonstrated in multiple randomized trials. However, despite successful recanalization of the primary occlusion, a proportion of patients continue to have persistent distal occlusions or incomplete reperfusion, which may limit neurological recovery. Residual distal occlusions, particularly in medium- and distal-vessel territories, remain an important and insufficiently studied contributor to suboptimal outcomes after thrombectomy. The optimal management of persistent distal occlusions after successful proximal thrombectomy remains uncertain. In current practice, some operators perform rescue distal mechanical thrombectomy, whereas others do not perform additional distal endovascular intervention because of concerns related to vessel injury, hemorrhagic complications, or prolonged procedure time. As a result, management remains variable and is not currently guided by high-level evidence. This is a randomized, controlled, open-label trial with blinded outcome assessment (PROBE design). Approximately 72 adult patients with acute ischemic stroke who undergo successful proximal mechanical thrombectomy but have one or more persistent distal occlusions will be enrolled. During the index endovascular procedure, eligible participants will be randomly assigned to one of two study groups: Rescue distal mechanical thrombectomy group: participants undergo rescue distal mechanical thrombectomy during the same endovascular session. Conservative management group: no additional distal endovascular intervention is performed after successful proximal mechanical thrombectomy. The primary objective of the study is to evaluate the feasibility and safety of rescue distal mechanical thrombectomy in this clinical setting. Secondary objectives include evaluating angiographic reperfusion, functional outcome at 90 days, early neurological improvement, and procedure-related safety outcomes. Because this study is conducted in an emergency stroke setting, the consent process is adapted to the participant's clinical condition. Whenever possible, informed consent is obtained directly from the participant before inclusion. If the participant lacks decision-making capacity, consent is obtained from an authorized representative, in accordance with applicable local regulations and ethics requirements. If decision-making capacity is regained, the participant is informed about the study and continued participation is confirmed according to the protocol. The trial is conducted at the Centre hospitalier de l'Université de Montréal (CHUM). All procedures included in the study are already used in routine clinical stroke care. Data are collected securely using the REDCap system, and imaging and clinical outcomes are assessed by independent evaluators blinded to treatment allocation. This phase II trial is intended to generate feasibility, safety, and preliminary outcome data to inform the design of a future larger study. The results may help guide treatment decisions for patients with persistent distal occlusions after proximal thrombectomy.
Interventions
PROCEDUREProximal mechanical thrombectomy
Mechanical thrombectomy performed for the qualifying proximal large vessel occlusion before assessment of eligibility for randomization.
PROCEDURERescue distal mechanical thrombectomy
Rescue distal mechanical thrombectomy performed during the same endovascular session after successful proximal recanalization to treat persistent distal medium-vessel occlusion identified on angiography.
No additional distal endovascular intervention after successful proximal mechanical thrombectomy. Participants continue with standard medical and post-procedural care.
Sponsors
Centre hospitalier de l'Université de Montréal (CHUM)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a Phase II, single-center, randomized, controlled, open-label trial with blinded outcome assessment (PROBE design). Participants with acute ischemic stroke and persistent distal occlusions after successful proximal mechanical thrombectomy are randomly assigned (1:1) during the index endovascular procedure to either rescue distal mechanical thrombectomy or conservative management. Randomization is stratified by age, thrombolysis use, and occlusion location. Although the treatment team is aware of treatment allocation, key angiographic and clinical outcomes are assessed by independent blinded evaluators. The study follows a pragmatic design with broad inclusion criteria and minimal protocol-imposed procedures beyond standard care.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Acute ischemic stroke with proximal large vessel occlusion (M1, M2, ICA, or basilar artery) treatable with mechanical thrombectomy * Presence of one or more persistent distal occlusions (M2-M4, A1-A5, or P1-P5) after successful proximal mechanical thrombectomy * The participant is considered suitable for either rescue distal mechanical thrombectomy or conservative management in the event of persistent distal occlusion * Informed consent obtained from the participant or authorized representative, in accordance with the protocol and local regulations
Exclusion criteria
* Poor expected 3-month prognosis due to comorbid conditions * Opposition by the participant or, in emergency inclusion circumstances, by an authorized representative
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants successfully randomized among screen-eligible participants | Periprocedural | Number of screen-eligible participants who are successfully randomized during the index endovascular procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median modified Rankin Scale (mRS) score at 90 days | 90 days | Median score on the modified Rankin Scale (0 to 6), where lower scores indicate less disability. |
| Proportion of functional independence as measured by the modified Rankin scale (0-2) | At 90 days | The modified Rankin Scale (mRS) is a 7-point ordinal scale (0-6) used to assess global disability and functional outcome, particularly after stroke. Scores range from 0 (no symptoms) to 6 (death), with higher scores indicating greater disability |
| Median change in NIHSS score (Delta NIHSS) | At 24 hours | The National Institutes of Health Stroke Scale (NIHSS) is a standardized 15-item neurological examination used to quantify stroke severity. Scores range from 0 to 42, with higher scores indicating more severe neurological deficits. It is widely used in clinical trials to assess baseline severity and early neurological outcomes. |
| Proportion of NIHSS improvement ≥ 4 points | At 24 hours | The National Institutes of Health Stroke Scale (NIHSS) is a standardized 15-item neurological examination used to quantify stroke severity. Scores range from 0 to 42, with higher scores indicating more severe neurological deficits. It is widely used in clinical trials to assess baseline severity and early neurological outcomes. |
| Median score of reperfusion (mTICI) | Immediate post-procedure. | Reperfusion will be assessed using the modified Thrombolysis in Cerebral Infarction (mTICI) scale (0-3) Higher grades indicate better reperfusion. Final angiographic outcomes will be adjudicated by a blinded core laboratory. |
| Rate of complete reperfusion (mTICI 3) | Immediate post procedure | Complete reperfusion is defined as mTICI grade 3 on final angiography, indicating full restoration of antegrade flow in the affected vascular territory. Assessment will be performed by a blinded core laboratory. |
| Procedure time | During the endovascular procedure | Procedure time is defined as the interval between arterial puncture and acquisition of the final angiographic run. It reflects procedural efficiency. |
| Number of intracranial thrombectomy passes | During the endovascular procedure | The number of device passes required to achieve final reperfusion during the endovascular procedure. Fewer passes may reflect higher procedural efficiency and effectiveness. |
| Disposition | At 90 days | Patient disposition at 90 days will be categorized as home, rehabilitation center, hospital, or death, reflecting post-stroke functional status and care needs |
| Rate of mortality | At 24 hours and 90 days | All-cause mortality will be assessed to capture early and late death following the index event and intervention |
| Rate of procedural complications | During the endovascular procedure | Procedural complications include vascular perforation, arterial dissection, and embolization to new vascular territories occurring during the endovascular procedure. |
| Median score of reperfusion (AOL) | immediate post-procedure | Reperfusion will be assessed using the modified Thrombolysis in Cerebral Infarction (AOL) scale (0-III) Higher grades indicate better reperfusion. Final angiographic outcomes will be adjudicated by a blinded core laboratory. |
Countries
Canada
Contacts
CONTACTGuylaine Gevry, BSc. Project manager
Outcome results
None listed