WSO - March 2024 - 369

Clarençon et al.
369
Introduction
Since 2016, after the publication of seven randomized controlled
trials (RCTs), mechanical thrombectomy (MT), in
combination with the best medical treatment (BMT), is recommended
for the treatment of acute ischemic stroke (AIS)
related to a large vessel occlusion (LVO) of the anterior
circulation.1 In these RCTs, the absolute risk reduction in
terms of favorable clinical outcome (defined as a modified
Rankin scale (mRS) ⩽2 at 3 months) ranged from 11% to
31% for the MT + BMT versus BMT arm. However, these
trials mainly included patients with proximal occlusions
and very few patients with a distal occlusion (0.5-14.3% of
M2 occlusions being included).1
To date, it remains unknown whether more distal occlusions
may benefit from MT. In addition, intravenous thrombolysis
has a relatively high rate of recanalization in distal
occlusions (up to about 50% recanalization rate).2 The aim
of the DISCOUNT trial is to evaluate the efficacy in terms
of good clinical outcome at 3 months of MT associated with
the BMT over the BMT alone in AIS related to a distal
occlusion.
Methods
Design
DISCOUNT is an academic-led multicenter open-label
RCT with blinded endpoint assessment (prospective randomized
open blinded endpoint (PROBE) design).
Patients are recruited in 22 high-volume comprehensive
stroke centers in France. All participating centers carry out
at least 100 thrombectomies per year and all operators have
already performed more than 30 endovascular MT procedures,
regardless of the technique used.
The trial is sponsored by Assistance Publique-Hôpitaux
de Paris and is carried out in accordance with the Declaration
of Helsinki, Good Clinical Practice and the French regulations.
The protocol was approved by the Comité de Protection
des Personnes (CPP) Ile de France 1 on 8 July 2021
(CPPIDF1-2021-ND51-cat.1) and by the competent authority
(Agence Nationale de Sécurité du Médicament (ANSM))
on 12 July 2021. This article is based on the protocol version
3.1 of 18 November 2022 after two substantial modifications
that were approved by the CPP Ile de France 1 on 14 February
2022 and 8 September 2022. These substantial modifications
concerned additional minimization on intravenous thrombolysis,
extension of the time window for patients with no
hyperintense signal on fluid-attenuated inversion recovery
(FLAIR) acquisition, and introduction of the possibility to
use aspiration catheters in addition to stent retrievers. This
trial is registered at ClinicalTrials.gov (NCT05030142). All
patients or their legal representatives have to provide written
informed consent. If the patient is not able to consent at
inclusion and his or her representative is not present, an
emergency consent procedure is implemented, and a pursuit
consent will be signed as soon as possible by the patient or if
not possible by his or her representative. The investigator at
each center is in charge of obtaining the consent from all
included participants.
Study population
The population that will be studied is adult patients
(⩾18 years of age) with an AIS secondary to a primary distal
intracranial artery occlusion, presenting within the 6 h
after the stroke onset, or within 24 h after last seen well if
the magnetic resonance imaging (MRI) FLAIR is negative
(i.e. no obvious hyperintense signal). We focus on this specific
population because no evidence is available on the
benefit of MT in distal occlusions, in contrast to more proximal
counterparts.
A clear definition of distal occlusion in AIS is lacking
in the literature. Anterior cerebral artery (ACA) and
posterior cerebral artery (PCA) occlusions are commonly
considered as distal occlusions.3,4 For the middle
cerebral artery (MCA), there is no consensus on
what a distal occlusion is.5 Thus, to enhance the homogeneity
of our study population, we decided to include
only distal M2 occlusions, defined as occlusion of
the M2 segment above the mid-height of the insula
(Supplemental Material 1). Distal occlusions were
therefore defined in the DISCOUNT trial as follows:
A1, A2, or A3 segment of the ACA; P1, P2, or P3 segment
of the PCA; distal M2 segment of the MCA; and
M3 MCA segment.
All consecutive patients will be evaluated like for any
routine AIS with an evaluation of significant past medical
history and a clinical assessment documenting National
Institute of Health Stroke Scale (NIHSS) score. Imaging
with computed tomography (CT) or MRI, according to
local standard practice, is required to exclude an acute
intracranial hemorrhage and to prove distal intracranial
occlusion (as defined above). Patients meeting the eligibility
criteria (Supplemental Material 2) will be included and
randomized.
Randomization and blinding
Intervention will be allocated 1:1 via a central web-based
randomization system (CLEANWEB) using a minimization
procedure accounting for center, age (<80 years old vs
⩾80 years old), NIHSS score at inclusion (<10 vs ⩾10),
IV thrombolysis (started or being started at randomization
vs no IV thrombolysis planned at randomization), and
occlusion site (distal MCA, ACA, and PCA). The minimization
scheme is prepared by the Clinical Research Unit
and implemented by the CLEANWEB team. The investigator
in each center enrolls patients and connects to the
CLEANWEB interface once a patient is included to randomize
the patient.
International Journal of Stroke, 19(3)
http://www.ClinicalTrials.gov
WSO - March 2024

Table of Contents for the Digital Edition of WSO - March 2024
