Developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke: study protocol for the Targeting Optimal Thrombolysis Outcomes (TOTO) multicentre cohort study
Introduction Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) is the only approved pharmacological reperfusion therapy for acute ischaemic stroke. Despite population benefit, IVT is not equally effective in all patients, nor is it without significant risk. Uncerta...
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BMJ Publishing Group
2020-04-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/10/4/e038180.full |
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| author | Elizabeth Holliday Timothy Kleinig Thomas Lillicrap Philip M C Choi Jane Maguire Andrew Bivard Lisa F Lincz Monica Anne Hamilton-Bruce Sushma R Rao Marten F Snel Paul J Trim Longting Lin Mark W Parsons Bradford B Worrall Simon Koblar Chris Levi |
| author_facet | Elizabeth Holliday Timothy Kleinig Thomas Lillicrap Philip M C Choi Jane Maguire Andrew Bivard Lisa F Lincz Monica Anne Hamilton-Bruce Sushma R Rao Marten F Snel Paul J Trim Longting Lin Mark W Parsons Bradford B Worrall Simon Koblar Chris Levi |
| author_sort | Elizabeth Holliday |
| collection | DOAJ |
| description | Introduction Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) is the only approved pharmacological reperfusion therapy for acute ischaemic stroke. Despite population benefit, IVT is not equally effective in all patients, nor is it without significant risk. Uncertain treatment outcome prediction complicates patient treatment selection. This study will develop and validate predictive algorithms for IVT response, using clinical, radiological and blood-based biomarker measures. A secondary objective is to develop predictive algorithms for endovascular thrombectomy (EVT), which has been proven as an effective reperfusion therapy since study inception.Methods and analysis The Targeting Optimal Thrombolysis Outcomes Study is a multicenter prospective cohort study of ischaemic stroke patients treated at participating Australian Stroke Centres with IVT and/or EVT. Patients undergo neuroimaging using multimodal CT or MRI at baseline with repeat neuroimaging 24 hours post-treatment. Baseline and follow-up blood samples are provided for research use. The primary outcome is good functional outcome at 90 days poststroke, defined as a modified Rankin Scale (mRS) Score of 0–2. Secondary outcomes are reperfusion, recanalisation, infarct core growth, change in stroke severity, poor functional outcome, excellent functional outcome and ordinal mRS at 90 days. Primary predictive models will be developed and validated in patients treated only with rt-PA. Models will be built using regression methods and include clinical variables, radiological measures from multimodal neuroimaging and blood-based biomarkers measured by mass spectrometry. Predictive accuracy will be quantified using c-statistics and R2. In secondary analyses, models will be developed in patients treated using EVT, with or without prior IVT, reflecting practice changes since original study design.Ethics and dissemination Patients, or relatives when patients could not consent, provide written informed consent to participate. This study received approval from the Hunter New England Local Health District Human Research Ethics Committee (reference 14/10/15/4.02). Findings will be disseminated via peer-reviewed publications and conference presentations. |
| format | Article |
| id | doaj-art-52c12dd6078c40b0b864537c9c00a0d6 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2020-04-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open |
| spelling | doaj-art-52c12dd6078c40b0b864537c9c00a0d62024-12-03T18:25:08ZengBMJ Publishing GroupBMJ Open2044-60552020-04-0110410.1136/bmjopen-2020-038180Developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke: study protocol for the Targeting Optimal Thrombolysis Outcomes (TOTO) multicentre cohort studyElizabeth Holliday0Timothy Kleinig1Thomas Lillicrap2Philip M C Choi3Jane Maguire4Andrew Bivard5Lisa F Lincz6Monica Anne Hamilton-Bruce7Sushma R Rao8Marten F Snel9Paul J Trim10Longting Lin11Mark W Parsons12Bradford B Worrall13Simon Koblar14Chris Levi154 CReDITSS, University of Newcastle Hunter Medical Research Institute, New Lambton, New South Wales, AustraliaNeurology & Stroke, Royal Adelaide Hospital, Adelaide, South Australia, AustraliaSchool of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, AustraliaDepartment of Neurosciences, Eastern Health, Box Hill, Victoria, AustraliaUniversity of Technology Sydney, Sydney, New South Wales, AustraliaMelbourne Brain Centre, Parkville, Victoria, AustraliaSchool of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, AustraliaStroke Research Programme, Central Adelaide Local Health Network, Adelaide, South Australia, AustraliaProteomics, Metabolomics and MS-imaging Core Facility, South Australian Health and Medical Research Institute, Adelaide, South Australia, AustraliaProteomics, Metabolomics and MS-imaging Core Facility, South Australian Health and Medical Research Institute, Adelaide, South Australia, AustraliaProteomics, Metabolomics and MS-imaging Core Facility, South Australian Health and Medical Research Institute, Adelaide, South Australia, AustraliaUniversity of New South Wales South Western Sydney Clinical School, Ingham Institute for Applied Medical Research, Department of Neurology, Liverpool Hospital, Sydney, New South Wales, AustraliaMelbourne Brain Centre, Parkville, Victoria, AustraliaDepartment of Neurology, University of Virginia, Charlottesville, Virginia, USAStroke Research Programme, The University of Adelaide, Adelaide, South Australia, AustraliaThe Sydney Partnership for Health, Education, Research & Enterprise (SPHERE), Sydney, New South Wales, AustraliaIntroduction Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) is the only approved pharmacological reperfusion therapy for acute ischaemic stroke. Despite population benefit, IVT is not equally effective in all patients, nor is it without significant risk. Uncertain treatment outcome prediction complicates patient treatment selection. This study will develop and validate predictive algorithms for IVT response, using clinical, radiological and blood-based biomarker measures. A secondary objective is to develop predictive algorithms for endovascular thrombectomy (EVT), which has been proven as an effective reperfusion therapy since study inception.Methods and analysis The Targeting Optimal Thrombolysis Outcomes Study is a multicenter prospective cohort study of ischaemic stroke patients treated at participating Australian Stroke Centres with IVT and/or EVT. Patients undergo neuroimaging using multimodal CT or MRI at baseline with repeat neuroimaging 24 hours post-treatment. Baseline and follow-up blood samples are provided for research use. The primary outcome is good functional outcome at 90 days poststroke, defined as a modified Rankin Scale (mRS) Score of 0–2. Secondary outcomes are reperfusion, recanalisation, infarct core growth, change in stroke severity, poor functional outcome, excellent functional outcome and ordinal mRS at 90 days. Primary predictive models will be developed and validated in patients treated only with rt-PA. Models will be built using regression methods and include clinical variables, radiological measures from multimodal neuroimaging and blood-based biomarkers measured by mass spectrometry. Predictive accuracy will be quantified using c-statistics and R2. In secondary analyses, models will be developed in patients treated using EVT, with or without prior IVT, reflecting practice changes since original study design.Ethics and dissemination Patients, or relatives when patients could not consent, provide written informed consent to participate. This study received approval from the Hunter New England Local Health District Human Research Ethics Committee (reference 14/10/15/4.02). Findings will be disseminated via peer-reviewed publications and conference presentations.https://bmjopen.bmj.com/content/10/4/e038180.full |
| spellingShingle | Elizabeth Holliday Timothy Kleinig Thomas Lillicrap Philip M C Choi Jane Maguire Andrew Bivard Lisa F Lincz Monica Anne Hamilton-Bruce Sushma R Rao Marten F Snel Paul J Trim Longting Lin Mark W Parsons Bradford B Worrall Simon Koblar Chris Levi Developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke: study protocol for the Targeting Optimal Thrombolysis Outcomes (TOTO) multicentre cohort study BMJ Open |
| title | Developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke: study protocol for the Targeting Optimal Thrombolysis Outcomes (TOTO) multicentre cohort study |
| title_full | Developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke: study protocol for the Targeting Optimal Thrombolysis Outcomes (TOTO) multicentre cohort study |
| title_fullStr | Developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke: study protocol for the Targeting Optimal Thrombolysis Outcomes (TOTO) multicentre cohort study |
| title_full_unstemmed | Developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke: study protocol for the Targeting Optimal Thrombolysis Outcomes (TOTO) multicentre cohort study |
| title_short | Developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke: study protocol for the Targeting Optimal Thrombolysis Outcomes (TOTO) multicentre cohort study |
| title_sort | developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke study protocol for the targeting optimal thrombolysis outcomes toto multicentre cohort study |
| url | https://bmjopen.bmj.com/content/10/4/e038180.full |
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