Evaluation of Mechanical Thrombectomy in Acute Ischemic Stroke Related to a Distal Arterial Occlusion (DISCOUNT)

Evaluation of Mechanical Thrombectomy in Acute Ischemic Stroke Related to a Distal Arterial Occlusion: a Randomized Controlled Trial

Mechanical thrombectomy (MT) has shown its effectiveness for the treatment of acute ischemic stroke (AIS) related to large vessel occlusion and rapidly became a cornerstone in the management of these patients. No strong evidence is available on the benefit of MT in AIS related to more distal occlusions. Some previous observational studies suggested a possible benefit but most of them were single-centre and retrospective studies providing a very low level of evidence. To date, no randomized controlled trial has been conducted in this indication, which represents 10% to 20% of all AIS involving intracranial vessel occlusions.

This research is a multicenter open randomized controlled trial with two parallel groups : best medical treatment alone VS mechanical trombectomy + best medical treatment.

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke (AIS) Related to a Distal Occlusion
• Intervention / Treatment: Procedure: Mechanical Thrombectomy; Drug: Best medical treatment alone

Detailed Description

The main objective of this trial is to assess the efficacy of mechanical thrombectomy in addition to the best medical treatment as compared to the best medical treatment alone in AIS related to a distal intracranial artery occlusion. The medical device used will be a stent retriever among : Trevor NXT ProVue Retriever ; Catchview mini ; pReset Lite ; Tigertriever13, and the medical treatment used will depend on the stroke's etiology and will consist of IV trhombolysis or tenecteplase or antiplatelet therapy or anticoagulant therapy ... The main inclusion criteria are : 1) patients aged ≥ 18 years ; 2) Delay between symptoms onset and expected groin puncture ≤ 6h ; 3) Symptomatic occlusion as evaluated by a National Institute of Health Stroke Score (NIHSS) ≥ 5 ; 4) Distal occlusion evaluated on CT angiography (CTA) or magnetic resonance imaging (MRI) and defined as an occlusion in one of the following segments : a-Distal M2, above the mid-height of the insula, b-M3 segment, c-Posterior cerebral artery (PCA) = P1, P2 or P3 segment, d-Anterior cerebral artery (ACA) : A1, A2 or A3 segment ; 5) Written informed consent signed by the patient or the trustworthy person / family member / close relative, or inclusion in case of emergency and written informed consent will be signed by the patient (if needed by trustworthy person, family member or close relative) as soon as possible (article L1122-1-2 of the French Public Health Code).

The secondary objectives and endpoints are to evaluate the : 1) Success of the procedure defined as recanalization of the occluded vessel, evaluated on the AOL (Arterial Occlusion Lesion) score within 48 hours ; 2) Excellent clinical outcome (defined as a modified Rankin scale [mRS]≤1) at 3 months ; 3) Safety with reporting of all adverse and serious adverse events with a particular attention to perforation rate, embolus migration in a new territory and symptomatic hemorrhagic complications ; 4) Death rate up to 3 months ; 5) Cost effectiveness and utility of the procedure. The study will also evaluate the rate of angiographic reperfusion in the intervention group on the final angiogram at the end of the MT (which is part of the intervention) using the modified thrombolysis in cerebral infarction (mTICI) (2B-3) and the eTICI.

• Study Type: Interventional
• Enrollment (Anticipated): 488
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Frédéric Clarençon, professor; Phone Number: + 33 1 42 16 35 43; Email: frederic.clarencon@aphp.fr
• Study Contact Backup: Name: Anne Radenne, Manager; Phone Number: + 33 1 42 16 16 99; Email: anne.radenne@aphp.fr

Study Locations

• France
  • Paris, France, 75013
    • Recruiting
    • Frédéric CLARENCON
    • Contact: Anne RADENNE; Phone Number: 0142161699

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients aged ≥ 18 years
• Delay between symptoms onset and expected groin puncture ≤ 6 h
• Symptomatic occlusion as evaluated by a National Institute of Health Stroke Score (NIHSS) ≥ 5

• Distal occlusion evaluated on CT angiography (CTA) or magnetic resonance imaging (MRI) and defined as an occlusion in one of the following segments:

  • Distal M2, above the mid-height of the insula
  • M3 segment
  • Posterior cerebral artery (PCA): P1, P2, P3 segments
  • Anterior cerebral artery (ACA): A1, A2, A3 segments
• Written informed consent signed by the patient or the trustworthy person / family member / close relative, or inclusion in case of emergency and written informed consent will be signed by the patient (if needed by trustworthy person, family member or close relative) as soon as possible (article L1122-1-2 of the French Public Health Code)

Exclusion Criteria:

• Pregnancy or breastfeeding woman
• Contra-indication for femoral, radial or humeral arterial puncture
• Tandem occlusion (i.e.: concomitant cervical and intra-cranial arterial occlusion)
• Allergy to iodinated contrast media
• Known renal insufficiency (confirmed by previous result of creatinine clearance < 30 ml/min)
• Secondary distal occlusion (i.e., complicating a MT for a proximal occlusion, or any other endovascular intracranial procedure)
• Aortic dissection
• Asymptomatic or minor stroke (i.e.: NIHSS < 5)
• Pretreatment mRS > 1 (pre-stroke)
• Anticipated limitations for anesthesia
• Participation in another trial (Jardé 1 and Jardé 2)
• Absence of affiliation to National French social security system
• Under legal protection measure (tutorship or curatorship) and patient deprived of freedom
• A pre-existing hemorrhage in the brain tissue fed by the target vessel
• Known hypersensitivity to nickel/titanium
• Stenosis and/or with a stent proximal to the site of the thrombus which could preclude the retrieval of the stent retriever
• Angiographic evidence of carotid dissection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mechanical thrombectomy; Mechanical thrombectomy (using a stent retriever among the following:Trevo NXT ProVue Retriever, Catchview mini, pReset Lite, Tigertriever 13) in association with the best medical treatment (usual care)	Procedure: Mechanical Thrombectomy; Mechanical thrombectomy (using a stent retriever among the following:Trevo NXT ProVue Retriever, Catchview mini, pReset Lite, Tigertriever 13) in association with the best medical treatment (usual care); Other Names: Experimental group
Active Comparator: Active Comparator; Best medical treatment alone (usual care)	Drug: Best medical treatment alone; Best medical treatment alone (usual care); Other Names: Control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Good clinical outcome (defined as a modified Rankin Scale [mRS] ≤ 2)	mRS of 0-2 (evaluated by an independent assessor blinded to the intervention received by the patient)	At 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recanalization of the occluded vessel	Evaluation of AOL (Arterial Occlusion Lesion scale) ≥ 2 on vascular brain imaging (magnetic resonance MR) or computed tomography (CT) angiography in patients belonging to both arms	48 hours after the mechanical thrombectomy
Angiographic reperfusion in the intervention group	Use of the mTICI score (successful reperfusion: mTICI 2b-3) and the eTICI (extended thrombolysis in cerebral infarction) score (successful reperfusion: eTICI ≥ 2b67) on the control digital subtraction angiography (DSA)	End of the mechanical thrombectomy procedure
Excellent Clinical outcome (defined as a modified Rankin Scale [mRS] ≤ 1)	mRS of 0-1 (evaluated by an independent assessor blinded to the intervention received by the patient)	At 3 months
Perforation rate	Defined as contrast material extravasation either on digital subtraction angiography [DSA] or control CT scan	End of mechanical thrombectomy procedure
Embolus migration in a new territory	evaluated on digital subtraction angiography [DSA]	End of mechanical thrombectomy procedure
Symptomatic intracranial hemorrhage	evaluated on CT-scan or MRI according to the ECASS II criteria	within 7 days
Subarachnoid hemorrhage	evaluated on CT-scan or MRI and define as the abnormal presence of blood within the subarachnoid space presence of blood within the subarachnoid space	within 48 hours
Safety : incidence of adverse events	Reporting of all adverse events	At 3 months
Safety : incidence of serious adverse events	Reporting of all serious adverse events	At 3 months
Death rate	Mortality	At 3 months
Utility of the procedure	Incremental cost utility ratio	At 3 months
Cost effectiveness	Cost per additional survivor (health-economics analysis)	At 3 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Frédéric Clarençon, Professor, APHP

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2021
• Primary Completion (Anticipated): February 14, 2024
• Study Completion (Anticipated): February 14, 2024

Study Registration Dates

• First Submitted: July 31, 2021
• First Submitted That Met QC Criteria: August 27, 2021
• First Posted (Actual): September 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 14, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Acute Ischemic Stroke; Mechanical Thrombectomy; Distal occlusions
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction
• Other Study ID Numbers: APHP200028; 2021-A00516-35 (Registry Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data are available upon reasonable request. The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
• IPD Sharing Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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