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Trial registered on ANZCTR

Registration number

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]

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

Condition category

Condition code

Stroke

Ischaemic

Physical Medicine / Rehabilitation

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]

Rehabilitation

Comparator / control treatment

Standard acute care (the standard rehabilitation care provided at the hospital)

Control group

Active

Outcomes

Primary outcome [1]

Modified Rankin Score

Timepoint [1]

At 3 months

Secondary outcome [1]

Death rate and the rate and severity of important medical events

Timepoint [1]

At 3 months

Secondary outcome [2]

All adverse events during the intervention period.

Timepoint [2]

Day 0 - Day 14

Secondary outcome [3]

Health related quality of life measure - AQoL

Timepoint [3]

3 and 12 months

Secondary outcome [4]

Cost effectiveness and cost utility

Timepoint [4]

At 3 and 12 months

Secondary outcome [5]

mRS

Timepoint [5]

At 12 months

Secondary outcome [6]

Dose response - Mobilisation dose and outcome. Therapy dose provided by therapists and nurses, and outcome as measured by Modified Rankin Score.

Timepoint [6]

3 months

Secondary outcome [7]

Staff injury during the intervention period

Timepoint [7]

Day 0 - Day 14

Secondary outcome [8]

Cognitive function using Montreal Cognitive Assessment (MoCA)

Timepoint [8]

At 3 months

Secondary outcome [9]

Time (days) to achieve unassisted walking over 50 metres

Timepoint [9]

3 months

Secondary outcome [10]

Length of hospitalisation (acute+ rehabilitation)

Timepoint [10]

3 months

Secondary outcome [11]

Mood measured using Irritability, Depression and Anxiety scale

Timepoint [11]

3 and 12 months

Secondary outcome [12]

Barthel Index

Timepoint [12]

3 and 12 months

Secondary outcome [13]

Proportion of patients walking unassisted

Timepoint [13]

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

Sex

Both males and females

Can healthy volunteers participate?

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

1/06/2006

Actual

18/07/2006

Date of last participant enrolment

Anticipated

Actual

16/10/2014

Date of last data collection

Anticipated

Actual

1/11/2016

Sample size

Target

2104

Accrual to date

Final

2104

Recruitment in Australia

Recruitment state(s)

NSW,QLD,SA,WA,VIC

Recruitment outside Australia

Country [1]

United Kingdom

State/province [1]

Scotland

Country [2]

Singapore

State/province [2]

Singapore

Country [3]

United Kingdom

State/province [3]

Northern Ireland

Country [4]

United Kingdom

State/province [4]

Wales

Country [5]

Malaysia

State/province [5]

Kuala Lumur

Country [6]

United Kingdom

State/province [6]

England

Country [7]

New Zealand

State/province [7]

Auckland

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

NHMRC grant

Address [1]

National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601

Country [1]

Australia

Primary sponsor type

Other

Name

National Stroke Research Institute

Address

245 Burgundy Street, Heidelberg VICTORIA 3084

Country

Australia

Secondary sponsor category [1]

University

Name [1]

Greater Glasgow Health Board

Address [1]

Dalian HOuse
350 St Vincent Street
Glasgow
G3 8YT

Country [1]

United Kingdom

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Austin Health

Ethics committee address [1]

145 Studley Road
Heidelberg, Victoria, AUSTRALIA 3084

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

26/05/2006

Ethics approval number [1]

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

A/Prof Julie Bernhardt

Address

Florey Institute of Neuroscience and Mental Health
245 Burgundy Street
Heidelberg, Victoria, 3084 Australia

Country

Australia

Phone

+61 3 9035 7072

Fax

61 3 9035 2251

j.bernhardt@unimelb.edu.au

Contact person for public queries

Name

Ms Fiona Ellery

Address

245 Burgundy Street, Heidleberg, Victoria 3084

Country

Australia

Phone

+613 9035 7042

Fax

+61 3 94962251

fellery@nsri.org.au

Contact person for scientific queries

Name

Julie Bernhardt

Address

245 Burgundy Street Heidelberg, VICTORIA 3084

Country

Australia

Phone

+613 9035 7072

Fax

+61 3 94962251

j.bernhardt@unimelb.edu.au

No information has been provided regarding IPD availability

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

Source	Title	Year of Publication	DOI
Dimensions AI	The Montreal Cognitive Assessment	2011	https://doi.org/10.1161/strokeaha.111.619486
Embase	AVERT2 (a very early rehabilitation trial, a very effective reproductive trigger): Retrospective observational analysis of the number of babies born to trial staff.	2015	https://dx.doi.org/10.1136/bmj.h6432
Embase	Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): A randomised controlled trial.	2015	https://dx.doi.org/10.1016/S0140-6736%2815%2960690-0
Embase	Exploring threats to generalisability in a large international rehabilitation trial (AVERT).	2015	https://dx.doi.org/10.1136/bmjopen-2015-008378
Embase	Prespecified dose-response analysis for A Very Early Rehabilitation Trial (AVERT).	2016	https://dx.doi.org/10.1212/WNL.0000000000002459
Embase	A very early rehabilitation trial after stroke (AVERT): a Phase III, multicentre, randomised controlled trial.	2017	https://dx.doi.org/10.3310/hta21540
Embase	Early mobilization after stroke is not associated with cognitive outcome findings from AVERT.	2018	https://dx.doi.org/10.1161/STROKEAHA.118.022217
Embase	Economic evaluation of a phase III international randomised controlled trial of very early mobilisation after stroke (AVERT).	2019	https://dx.doi.org/10.1136/bmjopen-2018-026230
Embase	Exploring post acute rehabilitation service use and outcomes for working age stroke survivors (<=65 years) in Australia, UK and South East Asia: Data from the international AVERT trial.	2020	https://dx.doi.org/10.1136/bmjopen-2019-035850
Embase	Utility-weighted modified Rankin Scale: Still too crude to be a truly patient-centric primary outcome measure?.	2020	https://dx.doi.org/10.1177/1747493019830583
Dimensions AI	Factors associated with time to independent walking recovery post-stroke	2021	https://doi.org/10.1136/jnnp-2020-325125
Embase	Factors associated with paid employment 12 months after stroke in A Very Early Rehabilitation Trial (AVERT).	2022	https://dx.doi.org/10.1016/j.rehab.2021.101565

N.B. These documents automatically identified may not have been verified by the study sponsor.

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