Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001432202
Ethics application status
Approved
Date submitted
24/07/2018
Date registered
27/08/2018
Date last updated
17/11/2022
Date data sharing statement initially provided
10/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Very Early Start to Personalised Upper limb Rehabilitation after stroke (VESPUR)
Scientific title
Very Early Start to Personalised Upper limb Rehabilitation after stroke (VESPUR)
Secondary ID [1] 295606 0
Nil
Universal Trial Number (UTN)
Trial acronym
VESPUR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
stroke 308926 0
Condition category
Condition code
Physical Medicine / Rehabilitation 307829 307829 0 0
Physiotherapy
Physical Medicine / Rehabilitation 307830 307830 0 0
Occupational therapy
Stroke 308072 308072 0 0
Ischaemic
Stroke 308073 308073 0 0
Haemorrhagic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
High dose upper limb rehabilitation will be delivered by a registered therapists (physiotherapist, occupational therapist, rehabilitation assistants). The dose of rehabilitation is 2-hours per weekday, for 50-weekdays over 10-weeks. Participants will be randomized to complete trhis dose early (between <=10-days to -3 months) or late (between 3- to 6-months). High dose upper limb motor rehabilitation will be distributed throughout the day (e.g., 15-20 minutes per session) to optimise the number of repetitions that can be completed, as well as support competing therapy demands. Our protocol focuses on impairment (e.g., strength, flexibility) and task-specific (e.g., reach, grasp) motor rehabilitation training. We will use assistive technologies considered standard of care in current stroke guidelines in Australia e.g., electrical stimulation as deemed suitable by the therapy team. Therapists will deliver rehabilitation according to a semi-supervised protocol, where a mix of fully supervised, semi-supervised and independent self-practice will be completed as able on an individual basis. All rehabilitation will be recorded on paper logs by therapist/s or the patient (and family, significant others).

When participants are not involved in the intervention rehabilitation protocol, they will receive standard rehabilitation that approximates 15 to 30 minutes/day from physiotherapists/occupational therapists at their local site. The dose of standard rehabilitation will be consistent across the early and late groups. If standard rehabilitation is not provided to a participant, one of our therapists will provide a self-practice program for 15 to 30 minutes/day to ensure that all participants receive the same therapy. All rehabilitation will be recorded on paper logs by the routine therapist/s or the patient (and family, significant others).
Intervention code [1] 301905 0
Rehabilitation
Comparator / control treatment
This trial has two active groups that are differentiated by time-post-stroke: motor training commencing early (<=10-days post-stroke); or Late (>3-months post-stroke). The comparator group will be Late.
Control group
Active

Outcomes
Primary outcome [1] 306806 0
Proportion of the participants who achieve the pre-specified good outcome at each of the defined trial stages.

A good outcome is defined as composite of:
- Achieving at least one of the following measures of:
o Change on Fugl Meyer Upper Limb (FM-UL) great than or equal to 9 points OR
o Change on Action Research Arm Test (ARAT) great than or equal to 12 points OR
o Change on Box and Block Test (BBT) great than or equal to 8 blocks

AND

- No SAEs causally attributable to intervention.

Clinical outcomes are consistent with a minimal clinical important difference (MCID) described in the literature. Given that MCID values were not always consistent with our cohort we made the following decisions:
•When MCID was informed by acute/subacute data we chose the minimum of the range, and
•When MCID was informed by chronic data, we chose the maximum of the range.
Timepoint [1] 306806 0
Baseline, 3-months and 6-months post stroke. Pre-intervention to post-intervention is primary endpoint.
Secondary outcome [1] 349701 0
Upper limb activity will be measured using the Action Research Arm Test.
Timepoint [1] 349701 0
Baseline, 3-months and 6-months post stroke
Secondary outcome [2] 349944 0
Upper limb impairment will be measured using the Fugl Meyer Upper Limb
Timepoint [2] 349944 0
Baseline, 3-months and 6-months post stroke
Secondary outcome [3] 349945 0
Upper limb dexterity will be measured using the Box and Block Test.
Timepoint [3] 349945 0
Baseline, serially (every week), 3-months and 6-months post stroke
Secondary outcome [4] 349946 0
Disability is assessed using the modified Rankin Scale.
Timepoint [4] 349946 0
Baseline, 3-months and 6-months post stroke
Secondary outcome [5] 349947 0
Quality of Life will be assessed using EQ-5D
Timepoint [5] 349947 0
Baseline, 3-months and 6-months post stroke
Secondary outcome [6] 349948 0
Stroke severity will be assessed using the National Institutes of Health Stroke Severity
Timepoint [6] 349948 0
Baseline, serially (every week for first month, every 2 weeks for 1-3 months, monthly up to 6-months), 3-months and 6-months post stroke
Secondary outcome [7] 403804 0
Feasibility of the intervention, defined as the proportion of the entire sample that could complete the high dose (2hrs/weekday) upper limb rehabilitation intervention protocol (Early or Late for 10-weeks). This will be determined from therapy paper logs and fidelity monitored session using video recordings.
Timepoint [7] 403804 0
Baseline, 3-months and 6-months post stroke
Secondary outcome [8] 403805 0
Safety of the intervention, defined as the number of adverse events across the first 6-months post-stroke. Possible adverse events include shoulder pain, fatigue etc. Events will be reported by patients, staff and research personnel, and reported on study specific forms.
Timepoint [8] 403805 0
Baseline, 3-months and 6-months post stroke

Eligibility
Key inclusion criteria
All patients admitted with stroke at each of the study sites during the recruitment period will be screened for eligibility against the following inclusion criteria:
- Hospital diagnosis of stroke confirmed by site neurologist using clinical scanning (CT/MRI),
- Aged >17 years,
- Upper limb impairment consistent with shoulder abduction and finger extension (SAFE) score >0 but <5 within 3-days of stroke (equivalent to a flicker or more, but less than antigravity movement),
- Able to undergo a motor evoked potential (MEP) evaluation, and
- Able to provide written informed consent; note, family consent will be sought from individuals with insufficient comprehension to consent, defined by a score >5 on Short Portable Mental State test.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded if they have:
- Had a previous stroke(s) in the motor area with residual deficits;
- Palliation or comorbid medical illness which in the opinion of the treating neurologist, it is deemed unlikely the patient will live 6-months or be able to actively participate in rehabilitation;
- Concomitant condition that would interfere with assessment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Early and Late groups will contain equal numbers overall, and of people who are MEP- and MEP+. The schedule will be stored off site and revealed by a blinded person.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Centralised computer generated random assignment procedure with permuted blocks of various sizes stratified by early motor pathway integrity (MEP+ and MEP-)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Analysis has two stages:
1. Stage 1 functions as a screening stage to determine if there is some indication of effect (ie at least 25% of the participants in a study achieving a good outcome per primary outcome description), and if it is worthy to continue enrollment into either the early and/or late study
2. Both Stage 1 and Stage 2 determines if early or late intervention is worthy investigating in a subsequent comparative group trial (ie at least 70% of participants achieving a good outcome per primary outcome description).

If there are too few good outcomes achieved the study, ie early or late, will be stopped. Otherwise, additional participants will be accrued for a total of 9 per study to examine achievement of a good outcome.

Our secondary analyses are estimates of effect with 95% CIs for all secondary outcomes. We will also investigate feasibility and acceptance by descriptively evaluating training logs for compliance, fidelity and adherence to dose by comparing training logs to video logs, as well as investigating recruitment and drop-out rates.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/09/2018
Actual
12/11/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
18
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 23493 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 300180 0
Charities/Societies/Foundations
Name [1] 300180 0
Stroke Foundation
Country [1] 300180 0
Australia
Funding source category [2] 300183 0
Charities/Societies/Foundations
Name [2] 300183 0
Heart Foundation
Country [2] 300183 0
Australia
Primary sponsor type
University
Name
Florey Institute of Neuroscience and Mental Health
Address
245 Burgundy Street, Heidelberg VIC 3083
Country
Australia
Secondary sponsor category [1] 299591 0
None
Name [1] 299591 0
Address [1] 299591 0
Country [1] 299591 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301012 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 301012 0
Studley Street, Heidelberg VIC 3083
Ethics committee country [1] 301012 0
Australia
Date submitted for ethics approval [1] 301012 0
02/05/2018
Approval date [1] 301012 0
17/07/2018
Ethics approval number [1] 301012 0
HREC/18/Austin/129

Summary
Brief summary
An early start to upper limb rehabilitation after stroke is critical to optimize functional outcomes. Our project aims to test this theory by delivery high dose upper limb rehabilitation, consistent with 2-hours of therapy in the first 6-months post-stroke. We will randomise participants to one of two groups based on our current understanding of the timing and biology of recovery: Early will start <10 days post-stroke and continue up to 3-months post-stroke, and Late will start 3-months post-stroke and continue to 6-months post-stroke. This study will identify if high dose upper limb rehabilitation in the first 6-months shows promise, is feasible and safe. Our study adopts an innovative approach to how we undertake rehabilitation trials in stroke.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85598 0
Dr Kathryn Hayward
Address 85598 0
Stroke Theme, Florey Institute of Neuroscience and Mental Health, 245 Burgundy Street, Heidelberg VIC 3083
Country 85598 0
Australia
Phone 85598 0
+61 3 9035 7293
Fax 85598 0
Email 85598 0
[email protected]
Contact person for public queries
Name 85599 0
Dr Kathryn Hayward
Address 85599 0
Stroke Theme, Florey Institute of Neuroscience and Mental Health, 245 Burgundy Street, Heidelberg VIC 3083
Country 85599 0
Australia
Phone 85599 0
+61 3 9035 7293
Fax 85599 0
Email 85599 0
[email protected]
Contact person for scientific queries
Name 85600 0
Dr Kathryn Hayward
Address 85600 0
Stroke Theme, Florey Institute of Neuroscience and Mental Health, 245 Burgundy Street, Heidelberg VIC 3083
Country 85600 0
Australia
Phone 85600 0
+61 3 9035 7293
Fax 85600 0
Email 85600 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.