The primary objective of this randomized trial is to determine whether patients experiencing an AIS due to an isolated medium vessel occlusion have superior functional outcome (measured with the mRS at 90 days) when treated with EVT plus BMT…
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the degree of dependency and disability in everyday life
(measured with the mRS) at 90 days.
Secondary outcome
Secondary efficacy outcomes include:
At 24 hours (± 6 h) post randomization:
- Normalized change in NIHSS
At 90 days (± 24 d) post randomization:
- Excellent functional outcome (mRS 0-1 versus mRS 2-6)
- Cognitive function (assessed with the Montreal Cognitive Assessment Test)
- Health-related quality of life (assessed with the Euro-Qol 5d)
At 1 year (±30 d) post randomization:
- Degree of disability and dependency (measured with the mRS)
- Health-related quality of life (assessed with the Euro-Qol 5d)
- Residential status
Safety outcomes include:
- sICH within 24 hours (defined with the modified SITS-MOST criteria)
- SAEs (neurological worsening, death, coma etc.) within 90 days
- Mortality at 90 days and 1 year.
Technical efficacy outcomes include:
- Percentage of brain tissue (penumbra) saved
- Successful reperfusion at end of EVT procedure, defined as eTICI 2b50-3
(assessed only in EVT+BMT patients)
- Recanalization of target artery at 24 hours (±6 h) post randomisation,
defined as Arterial Occlusion Lesion scale score 2-3 on CTA or MRA (assessed in
both EVT+BMT and BMT alone patients)
Background summary
Acute ischemic stroke (AIS) is one of the main causes of death and disability
and thereby the third leading cause of loss of quality adjusted life years. For
patients with an AIS due to an occlusion of the large vessels of the anterior
circulation, endovascular therapy (EVT) has become a treatment standard after
randomized trial evidence clearly showed dramatic clinical benefits with a
Number Needed to Treat of 2.6 for the reduction of disability and dependency in
daily activities.
However, 20-40% of all AIS patients have occlusions of smaller vessels and
present with a more distal isolated Medium Vessel Occlusion (MeVO).
Neurological outcome of MeVO patients is often poor, with rates of disability
and death exceeding 50% for some MeVO segments.
A meta-analysis based on subgroups of AIS patients with an M2 occlusion
included in seven randomized-controlled trials, indicated a positive treatment
effect of EVT with a relative increase in the proportion of patients being able
to continue a self-sustained life of 46.6% (58.2% intervention group vs 39.7%
control group). However, these analyses include only data from 131 patients and
most had occlusions of large, proximal M2 segments, not real MeVOs. Guidelines
have concluded that the data is insufficient to give a specific evidence-based
recommendation for or against EVT in case of M2 occlusions. For other distal
vessels, such as the M3 or M4 segment of the MCA or the ACA or the PCA no
randomized-controlled data is available at all.
As of now, no RCT has investigated the effectiveness and safety of EVT in
MeVOs. We hypothesize that EVT plus best medical treatment (BMT) is superior to
BMT alone with regard to long-term disability and dependency in daily life
(measured with the mRS at 90 days). In several retrospective and randomized
studies, there were no indications that relevant harmful functional outcome
effects (such as mortality or very severe disability) were associated with the
procedure.
Study objective
The primary objective of this randomized trial is to determine whether patients
experiencing an AIS due to an isolated medium vessel occlusion
have superior functional outcome (measured with the mRS at 90 days) when
treated with EVT plus BMT compared to patients treated with
BMT alone.
Secondary efficacy objectives are to study: at 90 days excellent functional
outcome (mRS 0-1), cognitive function and quality of life; at 24 hours after
randomization change in neurologic deficit severity, vessel patency and
salvaged brain tissue; and at 1 year level of dependency and disability in
daily life, quality of life and residential status. Safety objectives are to
study symptomatic intracranial haemorrhage within 24 hours, serious adverse
events, and 90 days and 1 year mortality.
Study design
Multicentre, pragmatic, international, parallel group, randomized (ratio 1:1),
open label, superiority trial with blinded endpoint assessment
Intervention
The intervention group will receive EVT + best medical treatment (including
iv-thrombolysis when appropriate). For EVT the choice
of device, access site and anaesthetic and antithrombotic management are per
local protocol or left to the discretion of the
interventionist. The control group will receive best medical treatment alone.
Study burden and risks
Burden and risk in intervention group: All patients in the intervention group
will be transferred to the angiosuite. The procedure involves catheterization
of the affected intracranial vessel.
There is no established indication, that the intervention causes harm beyond
local procedure related (arterial puncture site haemorrhage or (rarely) nerve
injuries) complications. However, it has been hypothesized, that symptomatic
intracranial haemorrhage (sICH), which is defined as a substantial haemorrhage
causing clinical deterioration occurs more often in patients undergoing EVT.
However, randomized-controlled data and large registries suggest, that EVT
poses no greater risk for the occurrence of sICH than BMT alone.
Burden and risk for all participants: All patients will undergo follow-up CT or
MRI scanning at 24h.
At 24h and at 7-10days all patients will undergo a neurological examination
(which is often part of standard care). At 3 months there will be a
neurological examination and short cognitive screening, which can be combined
with a regular followup and often is part of standard care.
At 3 and 12 months, all patients will be interviewed by telephone (about 30
minutes) to assess neurological and functional outcome.
Benefit: Thrombectomy is of potential benefit. The ultimate benefit would be
that patients maintain their life and health status as before the stroke.
Survival without neurological deficits would be associated with a better
quality of life in these patients.
Petersgraben 4
Basel CH-4031
CH
Petersgraben 4
Basel CH-4031
CH
Listed location countries
Age
Inclusion criteria
1. Acute ischemic stroke
2. Treatment (arterial puncture) can be initiated
2.1. Within 6 hours of last seen well (LSW)
OR
2.2. Within 6 to 24 hours of LSW AND
CT Criteria: Evidence of a hypoperfusion-hypodensity mismatch (Absence of
hypodensity on the non-contrast CT within >= 90% of the area of the hypoperfused
lesion on perfusion CT)
MRI Criteria: Evidence of a diffusion-hyperintensity mismatch (Absence of
hyperintensity on fluid-attenuated inversion recovery (FLAIR) imaging within >=
90% of the area of the diffusion weighted imaging (DWI) lesion)
3. Isolated medium vessel occlusion (i.e. an occlusion of the co-/non-dominant
M2, the M3/M4 segment of the MCA, the A1/A2/A3 segment of the ACA or the P1/P2
segment of the PCA) confirmed by CT or MRI Angiography
4. National Institute of Health Stroke Scale (NIHSS) Score of >= 4 points or
symptoms deemed clearly disabling by treating physician (i.e. aphasia,
hemianopia, etc.)
5. Age >=18 years
6. Deferred Written informed consent.
7. Agreement of treating physician to perform endovascular procedure
Exclusion criteria
1. Acute intracranial haemorrhage
2. Patient bedridden or presenting from a nursing home
3. In-Hospital Stroke
4. Known (serious) sensitivity to radiographic contrast agents, nickel,
titanium metals or their alloys
5. Foreseeable difficulties in follow-up due to geographic reasons (e.g.
patients living abroad)
6. Evidence of an ongoing pregnancy prior to randomization. A negative
pregnancy test before randomisation is required for all women with
child-bearing potential.
7. Known history of arterial tortuosity, pre-existing stent, other arterial
disease and/or known disease at the arterial access site that would prevent the
device from reaching the target vessel and/or preclude safe recovery after EVT
8. Known, severe comorbidities, which will likely prevent improvement or
follow-up (active cancer, alcohol/drug abuse or dementia)
9. Radiological confirmed evidence of mass effect or intracranial tumour
(except small meningioma)
10. Radiological confirmed evidence of cerebral vasculitis
11. Evidence of vessel recanalization prior to randomisation
12. Participation in another interventional trial
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT05029414 |
| CCMO | NL84673.078.23 |