WSO - July 2023 - 748

748
International Journal of Stroke 18(6)
will be unblinded. Contamination of stroke unit physiotherapy
and nursing practice will be minimized as details
of the intervention protocol will not be made publicly
available.
Patient population-inclusion and
exclusion criteria
Inclusion
Patients (⩾18 years) admitted to a stroke unit with ischemic
stroke (first ever or recurrent) within 48 h of stroke onset,
who are medically stable, with NIHSS < 17, pre-stroke
mRS < 3 and judged by the physiotherapist to have a mobility
problem are eligible. Participants may receive thrombolytic
and/or ECR.
Exclusion
Patients with hemorrhagic stroke or transient ischemic
attack (TIA), comorbid progressive neurological conditions,
severe heart failure, unstable coronary conditions or
any other condition that may pose a hazard, concurrent
diagnosis of rapidly deteriorating disease, deterioration following
admission, resulting in palliation or immediate surgery,
a lower limb fracture/disability (participant unable to
take part in mobility training), no evident acute stroke
mobility problems or expected discharge within 3 days
post-enrolment will be excluded. They cannot be participating
in another drug or intervention trial or be COVIDpositive
at time of enrolment.
Intervention
Trained ward physiotherapists and nurses work together to
provide protocolised mobility training sessions during the
intervention period, guided by the patient's functional level
as assessed daily by the therapists using the Mobility Scale
for Acute Stroke.8 Interventions commence after randomization
but within 48 h of stroke onset, with no minimum
wait time, and continue until the participant is discharged
from the stroke unit or 14 days post-randomization, whichever
is earlier. The mobility training protocol (provided
only to treating therapists and nurses) includes task-specific
mobility training (sitting, standing and walking) and functional
training of increasing intensity as the " active ingredient. "
Training task difficulty is progressed according to
patient status, similar to usual therapy prescription.
Activities lying down, or time spent in passive sitting out of
bed are not classed as mobility training. Training replaces
usual mobility-based care. In this dose finding trial we are
testing intervention amounts of between 10 and 40 min of
training per day, spread over 1-4 sessions, depending on
training arm. The reference arm has been prespecified as a
part of the design, is documented in the dose protocol, and
International Journal of Stroke, 18(6)
will be revealed at the final version of the Statistical
Analysis Plan document prior to the database lock. All
interventions (staff involved, time session commenced,
session number, mobility training activity, intensity of therapy
provided and minutes in therapy) are recorded in
REDCap.9
Primary outcomes
The primary outcome is the proportion of participants
experiencing a favorable outcome (mRS 0-2) at 3 months.
Secondary, tertiary, and
exploratory outcomes
Key secondary outcomes include; deaths at 3 months, severe
complications during the intervention period (< 14 days
post randomization), together with cost-effectiveness at
6 months. Unassisted ability to walk 50 m and walking speed
at 3 months, and quality of life at 3 months are among a
range of other recovery outcomes (tertiary and exploratory)
that can be found in the Supplemental material.
Studies within a trial (SWAT) will run alongside the
main trial. These studies explore genome wide association
analysis (GWA) and stroke recovery, service usage using
data linkage, cognitive reserve and outcome, imaging biomarkers,
and recovery of motor impairment.
Data monitoring body
A seven-member independent data safety monitoring committee
comprising research clinicians, neurologists, and a
statistician will meet regularly to review unblinded data.
Sample size estimates
Extensive simulations run for mild and moderate stroke
severity strata identified that the recruitment of 1300 participants
in the mild stratum and 1400 participants in the
moderate stratum would yield 80% power to observe 10%
risk difference or larger, when compared with the prespecified
reference arm in both strata (assuming 70% incidence
of mRS 0-2 outcome in the mild stratum prespecified reference
arm, and 30% incidence of mRS 0-2 outcome in the
moderate
stratum
prespecified
reference
arm),
with
Bonferroni corrected one-sided alpha family-wise threshold
p = 0.025 per stratum.
Adaptive sample size re-estimation will be undertaken
for both strata using Mehta and Pocock10 promising zone
methodology at the end of Stage 1 (i.e. once the 3-month
outcomes of 700 patients from a given stratum are available)
This will be based on the comparison between the reference
arm and the single intervention arm selected to
proceed to Stage 2. There will be a potential increase of up
WSO - July 2023

Table of Contents for the Digital Edition of WSO - July 2023
