WSO December 2023 – Issue 3 - 1258

1258
International Journal of Stroke 18(10)
cognitive functions (Montreal Cognitive Assessment, Trail
Making Test A and B, and STROOP Victoria test) at day 90,
and mRS score 0-1 rate in the experimental arm and the
control arm patients with secondary MT.
Safety outcomes include 90-day all-cause mortality,
symptomatic intracerebral hemorrhage at 24 h (according
to the Heidelberg classification),13 rapid worsening (NIHSS
score ⩾ 10), and procedure/device-related adverse events.
The health economic evaluation endpoints (definition
and analyses) will be presented in a separate document.
Data monitoring bodies
The study promoter (i.e. the Clinical Research and Innovation
Department, Montpellier University Hospital) is responsible
for monitoring the overall trial conduct. Data are collected in
electronic case report forms by the site personnel.
All serious adverse events will be reviewed by two monitors
who are members of the safety review committee.
The safety monitoring board (DSMB) includes one neurologist,
one neuroradiologist, and one methodologist who
do not participate in the MOSTE study and are not affiliated
with the sponsor. The executive committee and the
promoter decide whether to continue, hold, or stop the
study based on the DSMB recommendations.
Sample size estimates
A sample size of 412 patients/group will have 80% power to
detect an absolute increase of 10% in the 90-day mRS score
0-1 rate in the experimental arm by assuming a 60% rate of
mRS score 0-1 in the control arm, using a one-sided Z test
(normal approximation) at 0.025 significance level. This
number takes into account 5% of patients with missing primary
endpoint and the two interim efficacy/futility analyses
planned when 274 and 548 randomized patients, respectively,
will have completed the study, based on the O'Brien-Fleming
alpha spending function approach. The sample size can be
revised in the second interim analysis to address the uncertainty
concerning the mRS score 0-1 rate in the control arm,
estimated from retrospective observational studies.12,14-16
Statistical analyses
Statistical analyses will be independently performed using
the SAS 9.4 software (SAS Institute Inc, Cary, NC, USA).
The statistical analyses for the primary and secondary outcomes
are listed in the statistical analysis plan (Appendix,
Supplementary Online Content). Analyses will be performed
on all randomized patients in their assigned group,
according to the intention-to-treat principle. The primary
efficacy outcome analysis will be done using a generalized
linear mixed model with binomial distribution and logit
link function by including the center as a random effect and
all prognostic covariates considered in the minimization
International Journal of Stroke, 18(10)
randomization algorithm as fixed effects. Two efficacy and
safety interim analyses will be performed using the O'Brien
Fleming boundary for efficacy (superiority) or futility
approach. The final analysis will be performed with a significance
level (one-sided) of 0.023. No multiple comparisons
correction will be applied. All secondary objectives
and subgroup analyses will be considered as exploratory,
and results will be reported with only effect size estimates
and their two-sided 95% confidence intervals.
Study organization and funding
The study promoter is responsible for monitoring the overall
trial conduct. The executive committee is responsible
for the overall study design, interpretation, supervision,
including amendments, and provides guidance during
weekly video conferences. The industry sponsors (Stryker
Neurovascular, MicroVention, Medtronic, Cerenovus, and
Balt Extrusion) are not involved in the study design, supervision,
and publications.
Blinding
Treatment allocation is open; it is impractical to offer a
sham endovascular procedure.
Each site will designate an evaluator, blinded to randomization
and not involved in patient care, for the day-90
mRS scoring (primary endpoint). An independent core laboratory,
blinded to randomization, will review the neuroimaging
data (baseline and secondary endpoints).
Discussion
There are two ongoing randomized controlled trials on
patients with low NIHSS score and LVO (In Extremis/
MOSTE: NCT03796468, and ENDO-LOW: NCT04167525).
MOSTE enrolled its first patient in April 2019 and is expected
to complete enrollment in 2025. Using the highest trial
design standards and carefully monitored sites, it will produce
reliable and pivotal data on MT efficacy and safety for
patients with minor AIS and LVO. The primary outcome
metric (mRS score 0-1) is the most widely accepted in this
population. Due to the high risk of early neurological deterioration
in the control arm,2,3,10 the possibility of secondary
MT is included in the protocol after screening to verify eligibility.
Due to the risk of early postintravenous thrombolysis
recanalization, imaging re-assessment is mandatory for
transferred patients. Subgroups will be analyzed to assess the
influence of age, occlusion site, and time from last-seen-well
to randomization on MT efficacy and safety.
Summary and conclusion
Evidence on MT benefit in patients with NIHSS score ⩽ 5
and LVO is lacking. This large trial will provide
WSO December 2023 – Issue 3

Table of Contents for the Digital Edition of WSO December 2023 – Issue 3
