Evaluate Endovascular Treatment of Large Ischemic Stroke With Substantial Penumbra. (FrameLP)

French Acute Randomized Controlled Trial Using Multimodal Imaging for Endovascular Treatment of Patients With Large Cerebral Infarction With Substantial Penumbra up to 24 Hours

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

Study Overview

• Status: Terminated
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Procedure: Endovascular treatment in addition of best medical treatment.

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • Hôpital Pellegrin
  • Lille, France, 590370
    • University Hospital of Lille Hôpital Roger Salengro
  • Limoges, France, 87042
    • University Hospital of Limoges Hôpital Dupuytren 1
  • Montpellier, France, 34295
    • University Hospital of Montpellier Hôpital Gui de Chauliac
  • Nancy, France, 54000
    • University Hospital of Nancy (CHRU) Hôpital central
  • Paris, France, 75019
    • Fondation Adolphe de Rothschild Hospital
  • Paris, France, 75651
    • University Hospital Pitié-Salpétrière AP-HP
  • Suresnes, France, 92150
    • Foch Hospital Centre
  • Toulouse, France, 31059
    • University Hospital Toulouse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Strategy Group; endovascular treatment in addition to best medical treatment	Procedure: Endovascular treatment in addition of best medical treatment.; Endovascular treatment (EVT) of acute ischemic stroke (AIS) related to an anterior large cerebral vessel occlusion (LVO); Other Names: Mechanical thrombectomy
No Intervention: Control Strategy Group; best medical treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of patients achieving a functional recovery defined by modified Rankin Scale 0-2 at 3 months	Good functional outcome will be defined by a Modified Rankin Scale of 0-2, done by a certified rater, blinded of the arm of the randomization	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified Rankin Scale	Rate of patients with Modified Rankin Scale of 0-2 , rate of patients with Modified Rankin Scale 0-3 and Global disability assessed by overall distribution of the Modified Rankin Scale (shift analysis combining scores 5 and 6)	3 and 6 months
National Institute of Health Scale	Rate of patients achieving an early neurological improvement National Institutes of Health Stroke Scale (NIHSS) >or=8 reduction from baseline to day 1 or National Institutes of Health Stroke Scale (NIHSS) =0-1 at day 1	Day 1
Modified Thrombolysis in Cerebral Infarction score	Rate of successful reperfusion in the EndoVascular Treatment+Best medical treatment arm defined by a mTICI ( Modified Thrombolysis in Cerebral Infarction) 2bc3 score	Day 1
mortality rate	Number of subject who die during the study participation in each arm.	3 and 6 months
Symptomatic Hemorrhagic Transformation	Symptomatic hemorrhagic transformation is defined by an intra cerebral hemorrhage (European Cooperative Acute Stroke Study III classification " ECASS III ") associated with a 4 or more point increase on the National Institute of Health " NIH " Stroke Scale by comparison with NIH Stroke Scale immediately predeterioration.	36 hours

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Jean-Marc OLIVOT, MD PhD, University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2022
• Primary Completion (Actual): April 18, 2023
• Study Completion (Actual): April 18, 2023

Study Registration Dates

• First Submitted: July 11, 2022
• First Submitted That Met QC Criteria: September 13, 2022
• First Posted (Actual): September 14, 2022

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: June 8, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Thrombectomy; endovascular treatment; Acute ischemic stroke; large stroke; Multimodal brain imaging
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Ischemia
• Other Study ID Numbers: RC31/21/0336; 2021-A03139-32 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No