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Trial registered on ANZCTR


Trial ID
ACTRN12606000185561
Ethics application status
Approved
Date submitted
7/05/2006
Date registered
17/05/2006
Date last updated
9/01/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A Very Early Rehabilitation Trial
Scientific title
A Prospective Phase 3, multicentre, randomised controlled trial of efficacy (death and disability at 3 months) and cost effectiveness of very early rehabilitation (early and more frequent rehabilitation sessions) versus standard care (the rehabilitation care a patient would normally receive) in patients with acute stroke.
Secondary ID [1] 251716 0
No Secondary ID
Universal Trial Number (UTN)
U1111-1145-4204
Trial acronym
AVERT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 1158 0
Condition category
Condition code
Stroke 1242 1242 0 0
Ischaemic
Physical Medicine / Rehabilitation 1243 1243 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients are randomised to receive very early rehabilitation within 24 hours of the onset of stroke and for up to 14 days. The rehabilitation consists of protocol specified rehabilitation sessions of short duration, related to the patients normal activities of daily living. The rehabilitation is implemented by physiotherapists and nurses. Blinded assesssment of outcome is performed at 3 and 12 months.
Intervention code [1] 1024 0
Rehabilitation
Comparator / control treatment
Standard acute care (the standard rehabilitation care provided at the hospital)
Control group
Active

Outcomes
Primary outcome [1] 1677 0
Modified Rankin Score
Timepoint [1] 1677 0
At 3 months
Secondary outcome [1] 3008 0
Death rate and the rate and severity of important medical events
Timepoint [1] 3008 0
At 3 months
Secondary outcome [2] 3009 0
All adverse events during the intervention period.
Timepoint [2] 3009 0
Day 0 - Day 14
Secondary outcome [3] 3010 0
Health related quality of life measure - AQoL
Timepoint [3] 3010 0
3 and 12 months
Secondary outcome [4] 3011 0
Cost effectiveness and cost utility
Timepoint [4] 3011 0
At 3 and 12 months
Secondary outcome [5] 3012 0
mRS
Timepoint [5] 3012 0
At 12 months
Secondary outcome [6] 3014 0
Dose response - Mobilisation dose and outcome. Therapy dose provided by therapists and nurses, and outcome as measured by Modified Rankin Score.
Timepoint [6] 3014 0
3 months
Secondary outcome [7] 3016 0
Staff injury during the intervention period
Timepoint [7] 3016 0
Day 0 - Day 14
Secondary outcome [8] 9377 0
Cognitive function using Montreal Cognitive Assessment (MoCA)
Timepoint [8] 9377 0
At 3 months
Secondary outcome [9] 312761 0
Time (days) to achieve unassisted walking over 50 metres
Timepoint [9] 312761 0
3 months
Secondary outcome [10] 312762 0
Length of hospitalisation (acute+ rehabilitation)
Timepoint [10] 312762 0
3 months
Secondary outcome [11] 312763 0
Mood measured using Irritability, Depression and Anxiety scale
Timepoint [11] 312763 0
3 and 12 months
Secondary outcome [12] 312764 0
Barthel Index
Timepoint [12] 312764 0
3 and 12 months
Secondary outcome [13] 312765 0
Proportion of patients walking unassisted
Timepoint [13] 312765 0
3 and 12 months

Eligibility
Key inclusion criteria
First or recurrent stroke diagnosis, haemorrhage or infarct, admitted to a stroke unit within 24 hours of onset of stroke symptoms. Patients must at least react to verbal commands.
Minimum age
18 Years
Maximum age
Not stated
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pre stroke mRS of 3,4 or 5 (previous significant disability)Deterioration in patients condition in the first hour resulting in admission to ICU, surgery or documented palliative treatment.Concurrent diagnosis of rapidly deteriorating disease.Unstable coronary or other medical condition which is judged by the investigator to pose a hazard to the patient by involvement in the trial.A confirmed or suspected lower limb fracture preventing implemetation of the protocoltPA patients can be included if the treating physician permits and mobilisation within 24 hours is permitted.Patients cannot be concurrently recruited to drug or other intervention trials. Vital signs not within protocol specified normal limits.

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)
Allocation is concealed via a central web based randomisation system. Randomisation occurs once the patient provides consent. The AVERT physiotherapist and Nurse are aware of the allocation. The patient, other staff and specifically the assessor remain blinded to the allocation. All online information is secured by use of password site entry, and data encryption procedures.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permutated blocks of various lengths will be used to ensure allocation concealment. A secure remote web based computer generated randomisation will be used, statified according to stroke severity. (NIHSS 1-7 Mild), (NIHSS 8 - 16 Moderate), (NIHSS greater than 16 Severe).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The study is powered to detect an absolute risk reduction (ARR) of death or a poor outcome of 7.1% or greater, based on the following rationale: (i) consensus among investigators and international advisors that an ARR of this magnitude would represent a clinically meaningful effect size (although there are no formal cost-effectiveness data to support this view); and (ii) 3 month figures from an Australian hospital (40.9%) and a hospital that has practiced early mobilisation over many years (31.8%) showing less death and institutionalisation, therefore greater independent survival. Clinicians at this centre have estimated that mobilisation accounts for 78% of this 9.1% benefit. This gives a final absolute difference of 7.1%. A sample of 2104 patients (1052 per arm) will provide 80% power to detect a significant intervention effect (2 sided, p = 0.05) with adjustments for 5% dropping- in and a 10% dropping-out.
The primary efficacy hypothesis is tested using the binary logistic regression model with a treatment group as an independent variable and the 3 months mRS outcome (dichotomized into mRS 0-2 as favourable outcome and mRS 3-6 as poor outcome) as the dependent variable, including baseline NIHSS and age as treatment covariates for adjustment purposes. The treatment effect will be presented as odds ratio (OR) with the corresponding 95% CI. This analysis will allow comparison with published outcomes of other acute stroke trials.
Statisitical analysis plan for this trial will be published prior to the analysis of data.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment outside Australia
Country [1] 309 0
United Kingdom
State/province [1] 309 0
Scotland
Country [2] 310 0
Singapore
State/province [2] 310 0
Singapore
Country [3] 311 0
United Kingdom
State/province [3] 311 0
Northern Ireland
Country [4] 312 0
United Kingdom
State/province [4] 312 0
Wales
Country [5] 313 0
Malaysia
State/province [5] 313 0
Kuala Lumur
Country [6] 314 0
United Kingdom
State/province [6] 314 0
England
Country [7] 6625 0
New Zealand
State/province [7] 6625 0
Auckland

Funding & Sponsors
Funding source category [1] 1358 0
Government body
Name [1] 1358 0
NHMRC grant
Address [1] 1358 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 1358 0
Australia
Primary sponsor type
Other
Name
National Stroke Research Institute
Address
245 Burgundy Street, Heidelberg VICTORIA 3084
Country
Australia
Secondary sponsor category [1] 1199 0
University
Name [1] 1199 0
Greater Glasgow Health Board
Address [1] 1199 0
Dalian HOuse
350 St Vincent Street
Glasgow
G3 8YT
Country [1] 1199 0
United Kingdom

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 2715 0
Austin Health
Ethics committee address [1] 2715 0
145 Studley Road
Heidelberg, Victoria, AUSTRALIA 3084
Ethics committee country [1] 2715 0
Australia
Date submitted for ethics approval [1] 2715 0
Approval date [1] 2715 0
26/05/2006
Ethics approval number [1] 2715 0
H2006/02515

Summary
Brief summary
A Very Early Rehabilitation Trial (AVERT)
Randomised controlled trial of very early mobilisation (intervention) versus standard care (control) with blinded assessment of outcome and intention to treat anlaysis. A comprehensive cost eccectiveness sub study is included. It is hypothesised that early mobilisation of patients in addition to standard care alone, will reduce death and disability at 3 months, reduce the number and severity of stroke complications experienced by patients, resullt in a better quality of life and is cost effective.
Trial website
http://www.florey.edu.au/research/avert
Trial related presentations / publications
Bernhardt, J., Churilov, L., Dewey, H., Lindley, R., Moodie, M., Collier, J., Langhorne, P., Thrift, A., Donnan, G., for the AVERT Collaborators. (2015). Statistical Analysis Plan (SAP) for A Very Early Rehabilitation Trial (AVERT): An international trial to determine the efficacy and safety of commencing out of bed standing and walking training (very early mobilisation) within 24 h of stroke onset vs usual stroke unit care. [Journal]. International Journal of Stroke 10, 23-24.
Bernhardt, J., Langhorne, P., Lindley, R., Churilov, L., Thrift, A., Moodie, M., Collier, J., Ellery, F., Lennon, S., Hameed, S., Dewey, H., Donnan, G. (2015). A Very Early Rehabilitation Trial (AVERT): Primary outcome at 3 months post stroke. International Journal of Stroke, 10 (Suppl. 2), 2.
Bernhardt, J., Thrift, A., Dewey, H., Moodie, M., Lindley, R., Mc Rae, A., Tan, D., Lennon, S., Md Ali, K., Churilov, L., Collier, J., Langhorne, P., Donnan, G., on behalf of the AVERT Trialists' collaboration. (2015). A Very Early Rehabilitation Trial (AVERT): Primary Outcome. World Confederation for Physical Therapy, Singapore.
Donnan, G., Lindley, R., Thrift, A., Dewey, H., Langhorne, P., Bernhardt, J., on behalf of the AVERT Trialists' Collaboration. (2015). Progress update from A Very Early Rehabilitation Trial. Stroke, 46 (Suppl 1), ATP117.
The AVERT Trial Collaboration group. (2015). Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial. The Lancet, http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60690-0/abstract.
Public notes

Contacts
Principal investigator
Name 35466 0
A/Prof Julie Bernhardt
Address 35466 0
Florey Institute of Neuroscience and Mental Health
245 Burgundy Street
Heidelberg, Victoria, 3084 Australia
Country 35466 0
Australia
Phone 35466 0
+61 3 9035 7072
Fax 35466 0
61 3 9035 2251
Email 35466 0
j.bernhardt@unimelb.edu.au
Contact person for public queries
Name 10213 0
Ms Ms Fiona Ellery
Address 10213 0
245 Burgundy Street, Heidleberg, Victoria 3084
Country 10213 0
Australia
Phone 10213 0
+613 9035 7042
Fax 10213 0
+61 3 94962251
Email 10213 0
fellery@nsri.org.au
Contact person for scientific queries
Name 1141 0
A/Prof Julie Bernhardt
Address 1141 0
245 Burgundy Street Heidelberg, VICTORIA 3084
Country 1141 0
Australia
Phone 1141 0
+613 9035 7072
Fax 1141 0
+61 3 94962251
Email 1141 0
j.bernhardt@unimelb.edu.au