Clinical trial NCT05539404: Evaluate Endovascular Treatment of Large Ischemic Stroke With Substantial Penumbra.
Official title: French Acute Randomized Controlled Trial Using Multimodal Imaging for Endovascular Treatment of Patients With Large Cerebral Infarction With Substantial Penumbra up to 24 Hours
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Acute Ischemic Stroke
Keywords: Acute ischemic stroke
large stroke
Multimodal brain imaging
Thrombectomy
endovascular treatment
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2022-09-14
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Large cerebral infarctions are frequent and associated with a poor outcome. Previous cohort studies results suggest that patients with an acute ischemic stroke with large core and substantial penumbra on perfusion imaging benefit from EVT while those with no salvageable ischemic tissue did not. The Investigator aim to demonstrate in a randomized controlled trials (RCT) that EVT (Endo Vascular Treatment) in addition to BMT (Best Medical Treatment) increases the rate of functional recovery (mRS 0-2) at 3 months in patients with a LVO-related AIS with a large core and substantial penumbra evolving for less than 24hrs

Detailed description: The reperfusion of salvageable ischemic tissue (penumbra) to improve functional recovery is the aim of the endovascular treatment (EVT) of acute ischemic stroke (AIS) complicating large cerebral vessel occlusion (LVO). Downstream of an LVO, imaging profiles are highly variable ranging from a large completed infarction within 2 hrs to a small core and a large mismatch at 24 hrs after onset . A large core is typically associated with a poor prognosis and was a common exclusion criterion from the RCTs that demonstrated the efficacy of EVT for LVO related AIS . However the investigator recently reported that AIS with a large core 1- represent 20% of the LVO-related AIS scanned within 6 hours after onset 2- Up to 50% had a MM on perfusion imaging and 3- EVT increases the rate of functional recovery in patients with a large core over BMT only in the subgroup of patients with a MM (Mismatch) on baseline imaging .

One hundred and eighty patients experiencing an LVO-related AIS within 24 hours after last known well, with a documented large core (\>70mL) and a MM on baseline imaging will be randomized (1:1) to undergo EVT+BMT vs. BMT in a multicenter, randomized, controlled, open-label, in parallel groups with blinded endpoint evaluation (PROBE design) superiority trial.

Study participants will be followed up for 6 months. Participants will be treated and managed in acute stroke units by certified stroke neurologists and neurointerventionists according to the current recommendations . Neurological deficit will be assessed using the NIH Stroke Scale (NIHSS) by certified investigators.

Eligibility criteria: Inclusion Criteria:

* Patients experiencing an acute ischemic stroke related to an anterior proximal large vessel occlusion (ICA/M1/Tandem) on MR or CT-angiography evolving for less than 24 hours from last known to be well. For patients experiencing a wake-up stroke or a stroke of unknown onset the mid-point between last seen well and symptoms discovery + the delay between symptoms discovery to randomization, will be used to calculate the delay between symptom onset to randomization.
* On baseline imaging (MRI Diffusion Weighted Imaging/Perfusion Weighted Imaging or CTP) L.P. profile defined by a Large Core \> 70 mL, and a MM ratio\>1.4 using RAPID software.
* Delay between end of imaging and randomization \<90 min.
* Expected delay between end of imaging and femoral puncture \< 60 min
* Best medical treatment including IV thrombolysis if indicated
* Surrogate decision maker's consent or emergency inclusion form.
* Affiliated person or beneficiary of a social security scheme.

Exclusion Criteria:

* Pre-Stroke mRS \>1.
* Other serious advanced or terminal illness or life expectancy is estimated to be less than 6 months.
* Pre-existing medical, neurological or psychiatric condition that would confound the neurological or functional evaluation.
* Pregnancy and breastfeeding
* Inability to undergo contrast brain perfusion MR or CT.
* Technically inadequate perfusion imaging precluding L.P. profile assessment
* Occlusion in multiple proximal vascular site territories (eg. bilateral anterior circulation occlusion or anterior + posterior circulation occlusions).
* Known allergy to iodine precluding EVT.
* Vessel anatomy or tortuosity precluding EVT.
* Patient under judicial protection.
* Participation in another interventional or therapeutic study

Primary outcomes:
measure: Rate of patients achieving a functional recovery defined by modified Rankin Scale 0-2 at 3 months
timeFrame: 3 months
Secondary outcomes:
measure: modified Rankin Scale
timeFrame: 3 and 6 months
measure: National Institute of Health Scale
timeFrame: Day 1
measure: Modified Thrombolysis in Cerebral Infarction score
timeFrame: Day 1
measure: mortality rate
timeFrame: 3 and 6 months
measure: Symptomatic Hemorrhagic Transformation
timeFrame: 36 hours
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Hôpital Pellegrin
city: Lille
country: France
facility: University Hospital of Lille Hôpital Roger Salengro
city: Limoges
country: France
facility: University Hospital of Limoges Hôpital Dupuytren 1
city: Montpellier
country: France
facility: University Hospital of Montpellier Hôpital Gui de Chauliac
city: Nancy
country: France
facility: University Hospital of Nancy (CHRU) Hôpital central
city: Paris
country: France
facility: Fondation Adolphe de Rothschild Hospital
city: Paris
country: France
facility: University Hospital Pitié-Salpétrière AP-HP
city: Suresnes
country: France
facility: Foch Hospital Centre
city: Toulouse
country: France
facility: University Hospital Toulouse
Study officials:
affiliation: University Hospital, Toulouse
name: Jean-Marc OLIVOT, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: