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Trial registered on ANZCTR


Registration number
ACTRN12614000939695
Ethics application status
Approved
Date submitted
15/08/2014
Date registered
2/09/2014
Date last updated
17/12/2019
Date data sharing statement initially provided
17/12/2019
Date results information initially provided
17/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
T3 Trial: Triage, Treatment and Transfer of Patients with Stroke in Emergency Departments
Scientific title
A cluster randomised controlled trial to evaluate the effectiveness of a multidisciplinary organisational intervention to improve triage, treatment and transfer of acute stroke patients in Emergency Departments (EDs), relative to usual care, on death or dependency (defined as modified Rankin Scale [mRS] >=2) 90-days post hospital admission.
Secondary ID [1] 285172 0
APP1024812
Universal Trial Number (UTN)
U1111-1159-4170
Trial acronym
T3 Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 292766 0
Health services research 292767 0
Condition category
Condition code
Stroke 293056 293056 0 0
Ischaemic
Stroke 293057 293057 0 0
Haemorrhagic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
T3 Intervention
This organisational intervention will be implemented in Emergency Departments (EDs) and will target health care professional behaviour for acute stroke management. We will design evidence-based clinical protocols for triage, treatment and transfer following acute stroke. (Ai) routine assignment of stroke patients to triage Category 1 or 2; (Aii) time-sensitive ‘trigger’ screening for tPA eligibility; (Aiii) instigation of protocols for prompt management of fever, hyperglycaemia and swallowing; (Aiv) rapid transfer of patients from ED to the stroke unit. These protocols will be implemented using an evidence-based implementation strategy consisting of:
(Bi) workshops to identify local barriers and enablers and to identify clinical champions; (Bii) didactive and interactive education; (Biii) use of local clinical opinion leaders (site clinical champions); and (Biv) reminders in the form of email, telephone and site visits. The overall duration of the intervention period is anticipated to last for 12 to 18 months. Once we have recruited our required sample size the intervention period will cease.

For the duration of the trial, control group EDs will not receive any T3 Trial intervention elements.

As part of our intervention, site visits will be undertaken to discuss adherence to the intervention. This will be supported by email and telephone contact. Medical record audit will provide protocol adherence rates at the conclusion of the trial.
Intervention code [1] 290024 0
Treatment: Other
Comparator / control treatment
Usual care

Usual care will be the current treatment that stroke patients receive when admitted to EDs randomised to the control group. There will be no T3 trial intervention elements introduced at these sites.
Control group
Active

Outcomes
Primary outcome [1] 292927 0
Death or dependency (defined as modified Rankin Scale [mRS] >= 2)


Timepoint [1] 292927 0
Timepoint: 90-days post-hospital admission
Secondary outcome [1] 309959 0
Secondary Outcome 1:
Barthel Index [BI]) >= 95 (dependency score)

Timepoint [1] 309959 0
Timepoint: 90 days post hospital admission
Secondary outcome [2] 309960 0
Secondary Outcome 2:
mean SF-36 Physical Component Score [PCS]

Timepoint [2] 309960 0
Timepoint: 90 days post hospital admission
Secondary outcome [3] 309961 0
Secondary Outcome 3:
mean SF-36 Mental Component Score [MCS]

Timepoint [3] 309961 0
Timepoint: 90-days post-hospital admission

Eligibility
Key inclusion criteria
Cluster level (ED): Hospitals with EDs located in the Australian states of New South Wales, Queensland, Victoria and Australian Capital Territory

Patient level: English-speaking; admitted to the stroke unit via ED with a clinical diagnosis of ischaemic stroke or intracerebral haemorrhage; presented to hospital less than 48 hours from symptom onset; access to a telephone.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Presenting to hospital more than 48 hours from symptom onset; requiring palliative care only; identified non-cerebrovascular causes of acute focal neurological deficits (seizure, hypoglycaemia, toxic or metabolic encephalopathies); sub-arachnoid haemorrhage; and acute and chronic subdural haemorrhage.

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)
Cluster level: Cluster guardians will provide written informed cluster consent, agreeing that their ED can be randomised to either the intervention or control arm of the trial. They will agree to the intervention becoming ‘business as usual’ should they be allocated to the intervention group. This is in contrast to Emergency departments randomised to the control arm who will just continue usual care.

Patient level: Clinical Research Assistants (CRAs) at each study site who will be masked to trial design will enrol eligible patients. All eligible patients will be given a Patient Information Statement (PIS) outlining the collection of data and the 90 days follow-up process. This PIS outlines the opt-out consent process, with contact details provided to the study team for further questions or to opt-out.

As this is a cluster randomised controlled trial, randomisation of EDs and allocation to either intervention or control group will be conducted simultaneously – see below.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation will be based on clusters (EDs) rather than individuals. Each ED will be assigned a unique study number. EDs will be stratified by State and hospital baseline thrombolysis rates.

A list of participating EDs and stratification details will be provided in a de-identified format to an independent statistician not otherwise involved in the trial. Generation of the allocation sequence using random number generating software and assigning of EDs to either intervention or control group will be undertaken by this independent statistician.


Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
We plan to recruit 1160 patients from 26 clusters following implementation of the intervention and anticipate 9% loss to follow-up. With a 5% significance level and 80% power, assuming that 50% of patients in the usual care group will have mRS >=2, 60% will have Barthel Index >= 95, standard deviations for MCS and PCS of 11 and a design effect of 1.4 (the assumptions are based on our previous QASC Study), this will allow detection of a difference between intervention and control groups at 90 days post admission of:

10% for mRS >=2 (Primary outcome)

10% for Barthel Index [BI]) >= 95 (Secondary outcome 1);
0.2 standard deviations (~2.5 units) higher mean SF-36 Physical Component Score [PCS] (Secondary outcome 2); and
0.2 standard deviations (~2.5 units) higher mean SF-36 Mental Component Score [MCS] (Secondary outcome 3)

Analysis of outcomes will involve regression (logistic or linear as appropriate) with adjustment for clustering of patients within hospitals. We will undertake unadjusted analyses as well as analyses which adjust for baseline covariates. Primary analysis will be a complete case analysis with sensitivity analyses using multiple imputations to account for missing 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)
ACT,NSW,QLD,VIC
Recruitment hospital [1] 2859 0
The Canberra Hospital - Garran
Recruitment hospital [2] 2860 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [3] 2861 0
Bathurst Base Hospital - Bathurst
Recruitment hospital [4] 2862 0
John Hunter Hospital Royal Newcastle Centre - New Lambton
Recruitment hospital [5] 2863 0
Liverpool Hospital - Liverpool
Recruitment hospital [6] 2864 0
Nepean Hospital - Kingswood
Recruitment hospital [7] 2865 0
Prince of Wales Hospital - Randwick
Recruitment hospital [8] 2866 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [9] 2867 0
St George Hospital - Kogarah
Recruitment hospital [10] 2868 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [11] 2869 0
Westmead Hospital - Westmead
Recruitment hospital [12] 2870 0
Gold Coast Hospital - Southport
Recruitment hospital [13] 2871 0
Nambour General Hospital - Nambour
Recruitment hospital [14] 2872 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [15] 2873 0
The Townsville Hospital - Douglas
Recruitment hospital [16] 2874 0
The Wesley Hospital - Auchenflower
Recruitment hospital [17] 2875 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [18] 2876 0
Bendigo Health Care Group - Bendigo Hospital - Bendigo
Recruitment hospital [19] 2877 0
Box Hill Hospital - Box Hill
Recruitment hospital [20] 2878 0
Latrobe Regional Hospital - Traralgon
Recruitment hospital [21] 2879 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [22] 2880 0
Southwest Health Care - Warrnambool - Warrnambool
Recruitment hospital [23] 2881 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [24] 2882 0
Geelong Private Hospital - Geelong
Recruitment hospital [25] 2883 0
Northeast Health Wangaratta - Wangaratta
Recruitment hospital [26] 2884 0
The Alfred - Prahran
Recruitment postcode(s) [1] 8554 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 8551 0
2031 - Randwick
Recruitment postcode(s) [3] 8552 0
2050 - Camperdown
Recruitment postcode(s) [4] 8555 0
2145 - Westmead
Recruitment postcode(s) [5] 8549 0
2170 - Liverpool
Recruitment postcode(s) [6] 8546 0
2200 - Bankstown
Recruitment postcode(s) [7] 8553 0
2217 - Kogarah
Recruitment postcode(s) [8] 8548 0
2305 - New Lambton
Recruitment postcode(s) [9] 8545 0
2605 - Garran
Recruitment postcode(s) [10] 8550 0
2750 - Penrith
Recruitment postcode(s) [11] 8547 0
2795 - Bathurst
Recruitment postcode(s) [12] 8561 0
3004 - Melbourne
Recruitment postcode(s) [13] 8566 0
3050 - Royal Melbourne Hospital
Recruitment postcode(s) [14] 8568 0
3065 - Fitzroy
Recruitment postcode(s) [15] 8564 0
3128 - Box Hill
Recruitment postcode(s) [16] 8576 0
3181 - Prahran
Recruitment postcode(s) [17] 8569 0
3220 - Geelong
Recruitment postcode(s) [18] 8567 0
3280 - Warrnambool
Recruitment postcode(s) [19] 8563 0
3550 - Bendigo
Recruitment postcode(s) [20] 8570 0
3677 - Wangaratta
Recruitment postcode(s) [21] 8573 0
3844 - Traralgon
Recruitment postcode(s) [22] 8572 0
4006 - Herston
Recruitment postcode(s) [23] 8560 0
4066 - Auchenflower
Recruitment postcode(s) [24] 8556 0
4215 - Southport
Recruitment postcode(s) [25] 8571 0
4560 - Nambour
Recruitment postcode(s) [26] 8559 0
4810 - Townsville

Funding & Sponsors
Funding source category [1] 289783 0
Government body
Name [1] 289783 0
National Health and Medical Research Council (4PP1024812)



Address [1] 289783 0
National Health and Medical Research Council, GPO Box 1421, Canberra ACT 2601
Country [1] 289783 0
Australia
Primary sponsor type
Individual
Name
Prof Sandy Middleton
Address
Nursing Research Institute - SVHA (Syd) & ACU
Executive Suite, Level 5, deLacy Building
St Vincent's Hospital, Victoria Street, Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 288473 0
University
Name [1] 288473 0
Australian Catholic University


Address [1] 288473 0
PO Box 968, North Sydney, NSW, 2059
Country [1] 288473 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291513 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 291513 0
c/- Research Development Office
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 291513 0
Australia
Date submitted for ethics approval [1] 291513 0
Approval date [1] 291513 0
03/04/2012
Ethics approval number [1] 291513 0
HREC/12/RPAH/32
Ethics committee name [2] 291514 0
Australian Catholic University Human Ethics Research Committee
Ethics committee address [2] 291514 0
Locked Bag 4115, Fitzroy, VIC, 3065



Ethics committee country [2] 291514 0
Australia
Date submitted for ethics approval [2] 291514 0
Approval date [2] 291514 0
29/03/2012
Ethics approval number [2] 291514 0
2012 16N
Ethics committee name [3] 291515 0
Wangaratta Human Research Ethics Committee
Ethics committee address [3] 291515 0
PO Box 386 Wangaratta VIC 3676





Ethics committee country [3] 291515 0
Australia
Date submitted for ethics approval [3] 291515 0
Approval date [3] 291515 0
12/10/2012
Ethics approval number [3] 291515 0
111
Ethics committee name [4] 291516 0
South West Healthcare Multidisciplinary Ethics Committee
Ethics committee address [4] 291516 0
Ryot Street, Warrnambool, Vic, 3280



Ethics committee country [4] 291516 0
Australia
Date submitted for ethics approval [4] 291516 0
Approval date [4] 291516 0
09/10/2012
Ethics approval number [4] 291516 0
5/2012
Ethics committee name [5] 291517 0
Uniting Care Health, Human Research Ethics Committee
Ethics committee address [5] 291517 0
Upper Floor Moorland’s House, The Wesley Hospital, 451 Coronation Drive, Auchenflower, Qld, 4066



Ethics committee country [5] 291517 0
Australia
Date submitted for ethics approval [5] 291517 0
Approval date [5] 291517 0
11/12/2012
Ethics approval number [5] 291517 0
1231
Ethics committee name [6] 291518 0
ACT Government Health Directorate Human Research Ethics Committee
Ethics committee address [6] 291518 0
Building 10, Level 6, Canberra Hospital, PO Box 11, Woden, ACT, 2606

Ethics committee country [6] 291518 0
Australia
Date submitted for ethics approval [6] 291518 0
Approval date [6] 291518 0
04/02/2013
Ethics approval number [6] 291518 0
ETH.1.13.009

Summary
Brief summary
In 2011, members of our research team published the results of the Quality in Acute Stroke Care (QASC) Trial. This cluster randomised controlled trial evaluated the effectiveness of team-building workshops and education to introduce three clinical protocols to manage fever, sugar and swallowing (the FeSS protocols) in the acute stroke unit. We found that patients cared for in stroke units who received our intervention were 16% more likely to be alive and independent 90 days following their stroke. They also had fewer episodes of fever, lower mean temperatures, lower mean blood glucose levels, and better screening for swallowing difficulties. This landmark trial demonstrated that teamwork and good nursing care can improve patient outcomes.
Building on this previous work (1) we will evaluate using a cluster randomised controlled trial, an organisational intervention in EDs. Our evidence-based T3 Trial intervention will comprise: A) evidence-based clinical protocols for triage, treatment and transfer in acute stroke comprised of: (Ai) routine assignment of stroke patients to triage Category 1 or 2; (Aii) time-sensitive ‘trigger’ screening for tPA eligibility; (Aiii) instigation of protocols for prompt management of fever, hyperglycaemia and swallowing; (Aiv) rapid transfer of patients from ED to the stroke unit. To support implementation of the protocols we will use: B) an evidence based implementation strategy consisting of: (Bi) workshops to identify local barriers and enablers and to identify clinical champions; (Bii) didactive and interactive education; (Biii) use of local clinical opinion leaders (site clinical champions); and (Biv) reminders in the form of email, telephone and site visits.
This trial will be conducted in the EDs of hospitals with pre-existing dedicated stroke units in NSW, Victoria, Queensland and the ACT. EDs will be randomised to receive either the T3 Trial intervention or no additional support. At 90-days post-admission, we will measure death or dependency (mRS) (primary outcome); health status; and quality of life (secondary outcomes). A separate process analysis will examine contextual factors that may influence successful intervention uptake. Our novel and timely intervention will bridge the theory-practice gap aiming to deliver improvements in 90-day health outcomes for a group of patients currently underserved by evidence-based practice

Reference
1. Middleton S, McElduff P, Ward J, Grimshaw J, Dale S, D’Este C, Drury P, Griffiths R, Cheung NW, Quinn C, Evans M, Cadilhac D, Levi C. Implementation of evidence-based treatment protocols to manage fever, hyperglycaemia and swallowing dysfunction in acute stroke improves 90-day outcomes: QASC, a cluster randomised controlled trial. The Lancet 2011; 378 (9804): 1699-1706.
Trial website
Trial related presentations / publications
Published abstracts

Dale S, Martinez C, McInnes E and Middleton S. How ethical is the process of ethics and governance review for multi-site trials? Results from the T3 Trial. International Journal of Stroke. 2014; 9(S1) 13
S Middleton, CR Levi, C D’Este, J Grimshaw, DA Cadilhac, J Considine, W Cheung, L McInnes. S Dale, RP Gerraty, M Fitzgerald. T3 Trial protocol: A CRCT evaluating an organisational intervention to improve triage, treatment and transfer of stroke patients in EDs. International Journal of Stroke. 2013;8(S1) 4–10
Middleton S, Levi C, D’Este C, Grimshaw J, Cadilhac D, Considine J, Cheung W, McInnes L, Dale S, Gerraty R, Fitzgerald M, Cadigan G, Denisenko S, Longworth M, McElduff P, Quinn C. T3 stroke trial protocol: Triage, treatment and transfer of patients with stroke emergency departments. International Journal of Stroke. 2013;8(S2), 1–34

Conference Presentations

Dale S, Levi C, D’Este C, Grimshaw J, Cadilhac D, Considine J, Cheung W,McInnes E, Gerraty R, Fitzgerald M, Middleton S, on behalf of the T3 Trialists. Translating evidence in stroke care: The T3 Trial Protocol. 2nd Annual NHMRC Symposium on Research Translation 2013. Sydney 2-3 October 2013

Middleton S. Levi C, D’Este C, Cadilhac D, Considine J, Cheung W, McInnes E, Dale S, Quinn C on behalf of the T3 Trialists. Translating evidence in stroke care: The Triage, Treatment and Transfer Trial Study Protocol. 21st St Vincents & Mater Health Sydney Research Symposium. Sydney: 6 September 2013. P.21.[Fast Forward Presentation & poster].
** Winner Beckman Coulter Prize for Outstanding Poster Presentation**

Middleton S, Levi C, D'Este C, Grimshaw J, Cadilhac D, Considine J, Cheung W, McInnes E, Dale S & Gerraty R. T3 Stroke Trial Protocol: Triage, Treatment and Transfer of patients with stroke Emergency Departments. Smart Stroke Conference 2013. Brisbane; 22-23 August 2013.

Middleton S, Levi C, D'Este C, Grimshaw J, Cadilhac D, Considine J, Cheung W, McInnes E, Dale S & Gerraty R. T3 Trial Protocol: A CRCT evaluating an organisational intervention to improve Triage, Treatment and Transfer of stroke patients in ED's. Stroke Society of Australasia Annual Scientific Meeting 2013. Darwin, 31 July – 1 August 2013. [Poster]

Middleton S, Levi C,D’Este C, Grimshaw J, Cadilhac D, Considine J, Cheung W, McInnes E, Dale S, Gerraty R, & Fitzgerald M, on behalf of the T3 Trialists. T3 Stroke Trial: Protocol for a Cluster Randomised Controlled Trial to evaluate an organisational intervention to improve Triage, Treatment and Transfer of stroke patients in Emergency Departments. European Stroke Conference 2013. London, 28-31 May 2013. [Poster]
Public notes
Our trial has a pre-intervention observational phase to inform trial recruitment methods and obtain baseline data to inform randomisation and sample size estimation. Recruitment has not yet commenced for the randomised (post-intervention) phase of the trial.

Contacts
Principal investigator
Name 50714 0
Prof Sandy Middleton
Address 50714 0
Nursing Research Institute St Vincent’s Health Australia (Sydney) & Australian Catholic University, Executive Suite, Level 5, DeLacy Building, St Vincents Hospital, Victoria Road, Darlinghurst, NSW, 2010, Australia
Country 50714 0
Australia
Phone 50714 0
+61 2 83823790
Fax 50714 0
Email 50714 0
sandy.middleton@acu.edu.au
Contact person for public queries
Name 50715 0
Prof Sandy Middleton
Address 50715 0
Nursing Research Institute St Vincent’s Health Australia (Sydney) & Australian Catholic University, Executive Suite, Level 5, DeLacy Building, St Vincents Hospital, Victoria Road, Darlinghurst, NSW, 2010, Australia
Country 50715 0
Australia
Phone 50715 0
+61 2 83823790
Fax 50715 0
Email 50715 0
sandy.middleton@acu.edu.au
Contact person for scientific queries
Name 50716 0
Prof Sandy Middleton
Address 50716 0
Nursing Research Institute St Vincent’s Health Australia (Sydney) & Australian Catholic University, Executive Suite, Level 5, DeLacy Building, St Vincents Hospital, Victoria Road, Darlinghurst, NSW, 2010, Australia
Country 50716 0
Australia
Phone 50716 0
+61 2 83823790
Fax 50716 0
Email 50716 0
sandy.middleton@acu.edu.au

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 other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 6208 0
Middleton S, Dale S, Cheung NW, Cadilhac DA, Grimshaw JM, Levi C, et al. Nurse-initiated acute stroke care in emergency departments. Stroke. 2019;50:1346-1355
Attachments [1] 6208 0
Other publications
Have study results been made publicly available in another format?
Yes
Other publication details
Citation type [1] 6207 0
Conference abstract
Citation/DOI/link/details [1] 6207 0
Published abstract: Middleton S, Levi C, Dale S, Cheung NW, McInnes E, Considine J, D’Este C, Cadilhac DA, Grimshaw J, Gerraty R, Craig L, Schadewaldt V, McElduff P, Fitzgerald M, Quinn C, Cadigan G, Denisenk S, Longworth M, Ward J. The T3 Trial: Triage, Treatment and Transfer of patients with stroke in emergency departments. International Journal of Stroke 2017; 12(2): 15.
Results – basic reporting
Results – plain English summary