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Trial registered on ANZCTR


Registration number
ACTRN12613000939796
Ethics application status
Approved
Date submitted
22/08/2012
Date registered
26/08/2013
Date last updated
25/07/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Changing the health system to increase the adoption of "clot busters" in stroke treatment
Scientific title
Evaluating the effectiveness of a strategy to increase the adoption of best evidence practice. A cluster randomised controlled trial in acute stroke care.
Secondary ID [1] 280939 0
Nil
Universal Trial Number (UTN)
U1111-1145-6762
Trial acronym
TIPS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
stroke 286991 0
Condition category
Condition code
Stroke 287324 287324 0 0
Ischaemic
Public Health 287583 287583 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cluster randomised controlled trial of hospitals across New South Wales, Victoria and Queensland.

PRE-INTERVENTION PERIOD & POST-INTERVENTION PERIOD
Stroke care data including thrombolysis rates and stroke imaging will be obtained for a 24 month pre-intervention (baseline) period, followed by a 12 month intervention implementation period and then 12 months post-intervention data collection, with an additional 3 months for measurements of functional outcomes. Stroke care data and imaging for thrombolysed patients will be entered into the TIPS National Stroke Foundation database by staff from participating hospitals. Nurses and physicians from participating departments including Stroke Care Units (SCUs) and Emergency Departments will be invited to complete a pre-intervention survey regarding perceived barriers to thrombolysis implementation. This survey will be repeated during the follow-up phase. Rates of symptomatic intracranial haemorrhage and functional outcome will be assessed three months after thrombolytic treatment to ensure that rates are maintained at or below accepted benchmarks. Monitoring of adverse events will not interfere with established governance processes for reporting and monitoring of adverse events in the health system.

INTERVENTION
Intervention hospitals will receive a multi-component multidisciplinary collaborative intervention while control hospitals will follow usual care practices and are free to make practice changes of their own accord. The multicomponent intervention is based on thorough analysis of the steps, roles and barriers relating to rapid assessment for thrombolysis eligibility and collaborative implementation of a comprehensive range of strategies addressing change at the level of both the individual health professional and the health system. The intervention activities include pre-workshop meetings, collaborative communal workshops, site workshops and bi-weekly site meetings, web-based training modules, weekly case monitoring by telephone, bi-monthly performance feedback, and bi-monthly problem solving teleconferences.

Pre-workshop meetings: A meeting will be held at each hospital between the primary change agent and site champions at that hospital. The meeting will involve preliminary target setting for thrombolysis at the site, analysis of situational barriers to change and a readiness for change assessment. Meetings will be held prior to the first communal workshop.

Communal workshops: These two workshops will be held at the beginning and at the end of the intervention phase and will include the evidence base for thrombolysis, principles and components of the TIPS intervention, introduction to the TIPS educational website, setting overall and interim targets for thrombolysis, discussion of situational barriers and solutions to thrombolysis, action planning and change management strategies. The workshops will enable clinicians from different hospitals to work together and share their experiences in a team environment.

Site workshops: A site-workshop will be held shortly after each communal workshop. The aims of these two site-workshops are to ensure any team members not able to attend the communal workshops are brought up to date, and to provide an opportunity to gather further support for the project at each hospital by involving appropriate senior executives and staff members whose support may be important to achieve project goals.

Bi-weekly site meetings: The site working group, led by the site champions at each hospital, will include clinicians and executives with the ability to drive the project and communicate the changes to others. The aim of the meetings is to set targets, identify actions and review performance designed to achieve change in thrombolysis rates.

Web-based training modules: The TIPS website will include didactic training modules for clinicians with a test at the end of each module and a series of case studies where clinicians test their clinical judgement against a consensus-based logic frame for a randomly-chosen set of stroke cases. In each case the clinician is provided with feedback regarding the appropriateness of the decision and links to further reading if required. Clinicians are asked to continue with the case studies until they have achieved an agreed level of competence in decision making. Additional training modules will be provided for nurses (NET SMART) and paramedics (PAST). Some components of the training will remain available beyond the intervention phase to support sustainability.

Weekly case monitoring by telephone: During the intervention phase, the primary change agent will make weekly contact (by email or telephone) with site champions to discuss any questions or concerns relating to recent cases of thrombolysis.

Bi-monthly performance feedback: Hospitals will be provided with their 3-monthly estimated proportion of ischaemic stroke cases who receive thrombolysis, graphed against site targets. Comparative data will be provided, showing each hospital how it compares to other intervention hospitals in a de-identified format (e.g. other hospital names not disclosed), to create a positive level of competition among peers.

Bi-monthly problem solving teleconferences: Teleconference with primary change agent and site representatives for inter-site collaborative problem solving.

Throughout the intervention period there will be a focus on identifying and enacting strategies to embed relevant elements of the above into ongoing practice.

The intervention period for this project is 12 months, which is anticipated to commence late 2013.
Intervention code [1] 285347 0
Other interventions
Comparator / control treatment
PRE-INTERVENTION PERIOD & POST-INTERVENTION PERIOD
Stroke care data including thrombolysis rates and stroke imaging will be obtained for a 24 month pre-intervention (baseline) period, followed by a 12 month intervention implementation period and then 12 months post-intervention data collection. Stroke care data for thrombolysed patients will be entered into the TIPS National Stroke Foundation database and imaging into the INternational Stroke Perfusion Image REgistry (INSPIRE) by staff from participating hospitals. Physicians and nurses working in the Stroke Care Unit and Emergency Department in each of the 20 hospitals, will be invited to complete a pre-intervention survey regarding perceived barriers to thrombolysis implementation, which will be repeated post-intervention. Rates of symptomatic intracranial haemorrhage and functional outcome will be assessed three months after thrombolytic treatment to ensure that rates are maintained at or below accepted benchmarks. If, following the post-intervention period, the trialled intervention is found to be successful in improving study outcomes, it is envisaged that study protocols and processes will be made available to control sites.

INTERVENTION PERIOD
Control hospital sites will not be provided with any support to identify or implement change to current care processes during the study period. It is expected that usual care processes will occur. However control sites will not be required to commit to maintaining current protocols or processes.
Control group
Active

Outcomes
Primary outcome [1] 287599 0
The proportion of all stroke patients receiving thrombolysis at intervention hospitals, compared with control hospitals at follow-up.
Timepoint [1] 287599 0
Pre-intervention data will be obtained for a 24 month period; the intervention will then be implemented over 12 months. This is followed by a 12 months post-intervention data collection period.
Secondary outcome [1] 298504 0
Maintain best-practice benchmarks of 30% of patients achieving 3-month post stroke modified Rankin scores of 0-1 (little or no disability) at both intervention and control sites.
Timepoint [1] 298504 0
As for primary outcome timepoint with the addition of a three months post stroke window for patients treated during the study period.

Eligibility
Key inclusion criteria
Eligible hospitals are those with a Stroke Care Unit (or staffing equivalent of a stroke physician and stroke nurse) and an Emergency Department and where the hospital is at early stages of thrombolysis implementation. All participating hospitals are required to record all cases of thrombolysis for stroke, including adverse events and patient functional outcomes at three months. Both public and private hospitals are eligible to be included in the sample as are teaching and non-teaching hospitals.
Minimum age
No limit
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Hospitals without a stroke care unit or equivalent (stroke physician and stroke nurse)

Study design
Purpose of the study
Educational / counselling / training
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The Overall Principal Investigator and State-based leading neurologist/stroke physician champions will work collaboratively in recruiting 20 eligible hospitals to the study. Consent for participation will be obtained at the stroke care unit and hospital level. Initial contact with hospitals will be via personal contact (face-to-face, phone or email) from the research team. Written information sheets will be provided to explain the intended research study. Upon agreement to participate, a memorandum of understanding (MOU) or equivalent consent agreement will be signed between the site and the research team. Written invitation to complete the voluntary pre-intervention staff survey will be provided to a representative of each hospital who will distribute the surveys to relevant staff in person or by internal mail. Stroke Care Units will be stratified according to their stroke thrombolysis rates at baseline (very low, low, moderate). These strata were chosen as indicative of the factor most likely to influence the effect of the intervention on thrombolysis rates. Hospitals will be randomised at one time (effectively achieving allocation concealment) to either the intervention arm or the control arm with a 1:1 allocation ratio, using a computer generated stratified randomisation scheme in StatsDirect.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Eligible hospitals have been identified from National Stroke Foundation (NSF) audit records and from State-based clinical Stroke Care Unit networks. All hospitals will be randomised at one time to either the intervention arm or the control arm, using a computer generated stratified randomisation scheme (StatsDirect).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
During the 12 month intervention phase of the project, staff survey data and stroke thrombolysis data recorded by each hospital in the TIPS National Stroke Foundation database will be obtained from both intervention and control hospitals. Intervention hospitals will receive a range of intervention activities during this phase, while control hospitals will receive no intervention and are free to make practice changes of their own accord. If, following the post-intervention period, the trialled intervention is found to be successful in improving study outcomes, it is envisaged that study protocols and processes will be made available to control sites.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Primary outcome: The difference in thrombolysis rates between baseline (Year 1-2) and follow-up (Year 4) for intervention and control groups will be compared via a two-stage analysis adjusting for baseline thrombolysis rate using a stratified t-test. A secondary analysis will be undertaken excluding hospitals with moderate (>10%) baseline tPA rates, as there is limited potential for substantial further increase in these hospitals.

Secondary outcomes: The proportion of thrombolysed cases with good outcomes (mRS scores of 0-1) and the proportion with intracranial haemorrhage for each period at each hospital will be compared to benchmarks using a one tailed hypothesis test and analogous methods to stopping rules for randomised clinical trials. There will be intervention thresholds, beyond which quality assurance processes would be instituted, and stopping thresholds, beyond which tPA administration would be suspended until processes are reviewed. Because we are conducting three analyses, we have used the method of O’Brien-Fleming to determine significance levels for each of the three analyses (this method provides more stringent stopping criteria for early analysis). The appropriate significance levels are 0.0006, 0.0151 and 0.0471 for analysis 1, 2 and 3 respectively.

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,VIC

Funding & Sponsors
Funding source category [1] 285698 0
Other Collaborative groups
Name [1] 285698 0
National Health and Medical Research Council (NHMRC)
Address [1] 285698 0
GPO Box 1421, Canberra ACT 2601
16 Marcus Clarke Street, Canberra City ACT 2600
Country [1] 285698 0
Australia
Primary sponsor type
University
Name
The University of Newcastle
Address
Health Behaviour Research Group
School of Medicine and Public Health
W4, HMRI Building
Callaghan NSW 2308
Country
Australia
Secondary sponsor category [1] 284533 0
Commercial sector/Industry
Name [1] 284533 0
Boehringer Ingelheim
Address [1] 284533 0
78 Waterloo Road
North Ryde, NSW 2113
Australia

PO Box 1969
Macquarie Centre, NSW 2113
Australia
Country [1] 284533 0
Australia
Secondary sponsor category [2] 284534 0
Charities/Societies/Foundations
Name [2] 284534 0
National Stroke Foundation
Address [2] 284534 0
Level 7, 561 Bourke Street, Melbourne VIC 3000
Country [2] 284534 0
Australia
Secondary sponsor category [3] 284535 0
Government body
Name [3] 284535 0
ACI Stroke Network
Address [3] 284535 0
Tower A, Level 15
Zenith Centre
821-843 Pacific Highway
Chatswood NSW 2067

Previously known as Stroke Services NSW, NSW Department of Health, Level 3, 51 Wicks Road, North Ryde NSW 2112
Country [3] 284535 0
Australia
Secondary sponsor category [4] 284536 0
Charities/Societies/Foundations
Name [4] 284536 0
National Heart Foundation of Australia (NSW Division)
Address [4] 284536 0
Level 3, 80 William Street, Sydney NSW 2011
Country [4] 284536 0
Australia
Secondary sponsor category [5] 284537 0
Government body
Name [5] 284537 0
Victorian Stroke Clinical Network, Victorian Department of Health
Address [5] 284537 0
50 Lonsdale Street, Melbourne, Victoria 3000
Country [5] 284537 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287706 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 287706 0
Hunter New England Research Ethics & Governance Unit
Locked Bag No 1
New Lambton NSW 2305
Ethics committee country [1] 287706 0
Australia
Date submitted for ethics approval [1] 287706 0
Approval date [1] 287706 0
24/06/2010
Ethics approval number [1] 287706 0
HREC/10/HNE/132
Ethics committee name [2] 287707 0
Darling Downs Health Service District Human Research Ethics Committee
Ethics committee address [2] 287707 0
Darling Downs Health Services District
The Undercroft
Mount Lofty Heights Nursing Home
Rifle Range Road
TOOWOOMBA QLD 4350
Ethics committee country [2] 287707 0
Australia
Date submitted for ethics approval [2] 287707 0
Approval date [2] 287707 0
30/09/2011
Ethics approval number [2] 287707 0
HREC/11/QTDD/44
Ethics committee name [3] 287708 0
Sydney Adventist Hospital Group Human Research Ethics Committee
Ethics committee address [3] 287708 0
185 Fox Valley Road
Wahroonga NSW 2076
Ethics committee country [3] 287708 0
Australia
Date submitted for ethics approval [3] 287708 0
Approval date [3] 287708 0
28/03/2012
Ethics approval number [3] 287708 0
2011-041
Ethics committee name [4] 287709 0
Epworth HealthCare Board of Management
Ethics committee address [4] 287709 0
89 Bridge Road
Richmond VIC 3121
Ethics committee country [4] 287709 0
Australia
Date submitted for ethics approval [4] 287709 0
Approval date [4] 287709 0
23/05/2012
Ethics approval number [4] 287709 0
55412
Ethics committee name [5] 287710 0
LaTrobe Regional Hospital Human Research Ethics Committee
Ethics committee address [5] 287710 0
Latrobe Regional Hospital
PO Box 424
TRARALGON VIC 3844
Ethics committee country [5] 287710 0
Australia
Date submitted for ethics approval [5] 287710 0
Approval date [5] 287710 0
06/12/2011
Ethics approval number [5] 287710 0
2011-04
Ethics committee name [6] 287711 0
Peninsula Health Human Research Ethics Committee
Ethics committee address [6] 287711 0
PO Box 52
Frankston VIC 3199
Ethics committee country [6] 287711 0
Australia
Date submitted for ethics approval [6] 287711 0
Approval date [6] 287711 0
17/01/2011
Ethics approval number [6] 287711 0
HREC/10/PH/53 (part 1) HREC/12/PH/32 (part 2)
Ethics committee name [7] 287880 0
Melbourne Health
Ethics committee address [7] 287880 0
Office for Research
6 East, Central Building
The Royal Melbourne Hospital
300 Grattan Street
PARKVILLE VIC 3050
Ethics committee country [7] 287880 0
Australia
Date submitted for ethics approval [7] 287880 0
14/12/2010
Approval date [7] 287880 0
Ethics approval number [7] 287880 0
2010.238 (part 1) and 2012.114 (part 2)

Summary
Brief summary
This study will examine whether a hospital-focussed multicomponent multidisciplinary collaborative approach can increase stroke thrombolysis rates, while maintaining accepted benchmarks for low rates of intracranial haemorrhage and high rates of functional outcome at three months. The approach will be tested using a cluster randomised controlled trial involving 20 hospitals in the early stages of thrombolysis implementation.

Outcomes will include thrombolysis rates in intervention and control hospitals at follow up as well as intracranial haemorrhage rates and functional outcomes at 3 months.
Trial website
Trial related presentations / publications
Paul CL et al. Thrombolysis ImPlementation in Stroke (TIPS): evaluating the effectiveness of a strategy to increase the adoption of best evidence practice – protocol for a cluster randomised controlled trial in acute stroke care. Implementation Science, 25 March 2014, doi:10.1186/1748-5908-9-38

Paul, Christine L., et al. "How can we improve stroke thrombolysis rates? A review of health system factors and approaches associated with thrombolysis administration rates in acute stroke care." Implementation Science 11.1 (2016): 51.

Kawano H, Bivard A, Parsons MW, Paul CL, Krause M, et al. (2017) Hospital Arrival Times and Post-Imaging Delays in Stroke Thrombolysis Implementation. J Neurol Disord Stroke 5(3): 1127

C. Levi, R. Sanson-Fisher, J. Attia, A. Bivard, M. Parsons, N. Spratt, S. Middleton, C. Bladin, R. Lindley, E. Kerr, A. Ryan, G. Donnan, C. Oldmeadow, K. Morris, M. Russell, M. Evans and C. Paul. Thrombolysis ImPlementation in Stroke (TIPS) Trial: A cluster randomised control trial of implementation strategies for intravenous thrombolysis. European Stroke Journal. 2017;2(Suppl 1):9.
Public notes

Contacts
Principal investigator
Name 34484 0
Prof Rob Sanson-Fisher
Address 34484 0
Health Behaviour Research Group
School of Medicine and Public Health
University of Newcastle
W4, HMRI Building
Callaghan NSW 2308
Country 34484 0
Australia
Phone 34484 0
+61 2 4042 0713
Fax 34484 0
Email 34484 0
Rob.Sanson-Fisher@newcastle.edu.au
Contact person for public queries
Name 17731 0
A/Prof Christine Paul
Address 17731 0
Health Behaviour Research Group
School of Medicine and Public Health
University of Newcastle
W4, HMRI Building
Callaghan NSW 2308
Country 17731 0
Australia
Phone 17731 0
+61 2 40420693
Fax 17731 0
Email 17731 0
Chris.Paul@newcastle.edu.au
Contact person for scientific queries
Name 8659 0
A/Prof Christine Paul
Address 8659 0
Health Behaviour Research Group
School of Medicine and Public Health
University of Newcastle
W4, HMRI Building
Callaghan NSW 2308
Country 8659 0
Australia
Phone 8659 0
+61 2 40420693
Fax 8659 0
Email 8659 0
Chris.Paul@newcastle.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary