Saving Brain and Changing Practice in Stroke

• 
  Project Lead
  Professor Stephen Davis

  stephen.davis@mh.org.au

  View researcher's webpage

  +61 3 9342 8448

Project Details

Stroke is a massive global health challenge. With 17 million new strokes each year and 6 million deaths, stroke is a leading cause of chronic disability. Stroke is the second commonest cause of death worldwide and the leading cause of death in 39% of countries. We have shown that effective acute stroke therapies modify the dynamic evolution of stroke pathophysiology. Following arterial occlusion, most patients have a mismatch between the region of the irreversibly injured ischemic core and the surrounding region of hypoperfused but salvageable brain. This ischemic penumbra is the target of acute stroke therapy. Reperfusion strategies that attenuate infarct growth include IV tPA and now endovascular thrombectomy for large artery occlusion. Our pathophysiological research has confirmed the principle that ‘time is brain’, and hence our overall research strategy will now focus on the patient journey from the time of acute stroke pre-hospital through to recovery.

OVERALL PROGRAM AIM: To provide evidence that will change international practice in stroke. To track the stroke journey from onset to recovery, initiate treatment pre-hospital, expand acute hospital management, enhance brain recovery and implement changes in health policy.

Aim 1: PRE-HOSPITAL INTERVENTIONS: “THE GOLDEN HOUR”. Using the paradigm that “time is brain”, we will utilise technological advances in the pre-hospital setting to test current and novel interventions likely to lead to improved clinical outcomes.

Aim 2: ACUTE HOSPITAL INTERVENTIONS: THE NEXT FRONTIER. To expand our current strategy using advanced brain imaging to identify treatment responders in ischemic stroke. This will include validating a new IV lytic (TNK), direct endovascular intervention, and increasing the population for current strategies (IV tPA 4.5-9 hours and wake-up stroke).

Aim 3: BRAIN RECOVERY: DRUG INTERVENTIONS AND BIOMARKERS. To determine which imaging and blood-based biomarkers will predict a favourable response to treatment with fluoxetine on functional outcome after stroke.

Aim 4: CHANGING PRACTICE: IMPLEMENTATION TO IMPROVE OUTCOMES. To identify optimal strategies for triage and management of patients by utilising reperfusion therapies. These are aimed at increasing uptake of tPA and endovascular thrombectomy in Australia

Researchers

• Dr Nawaf Yassi, Neurologist
• Dr Henry Zhao, Neurologist
• David Jackso, Research Nurse
• Amy Mcdonald, Research Nurse
• Skye Coote, Senior Mobile Stroke Unit Research Nurse
• Dr Edrich Rodrigues, Fellow
• Dr Patrick Silvaris, Fellow
• Lauren Pasavento, Research Nurse
• Smisha Thomas, Stroke Database Manager

Collaborators

• Professor Geoffrey Donnan, Director Florey Institute of Neuroscience and Mental Health
• Professor Graeme Hankey, University of Western Australia
• Professor Mark Parsons, University of Newcastle
• Professor Chris Levi, University of Newcastle
• Associate Professor Bruce Campbell, Royal Melbourne Hospital
• Professor Craig Anderson
• Professor Julie Bernhardt, Lead of the NHMRC Centre for Research Excellence in Rehabilitation and Brain Recovery
• Professor Christopher Bladin, Monash University/The Florey Institute
• Associate Professor Dominique Cadilhac, Head of Translational Public Health, Stroke and Ageing Research, Department of Medicine at Monash University; and Head of Public Health, Stroke Division, The Florey Institute.
• Professor Stephen Bernard, Alfred Health
• Professor Leeanne Carey, Florey Institute
• Professor Leonid Churilov, Head of Statistics at The Florey Institute
• Associate Professor David Howells, University of Tasmania
• Professor Atte Meretoja, Helsinki University Hospital
• Associate Professor Peter Mitchell

Funding

• National Health and Medical Research Council Program Grant

Research Publications

1. Campbell BC, Mitchell PJ, Kleinig TJ ... Donnan GA*, Davis SM*. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015; 372:1009-1018 *Cochairs, Steering Committee (IF: 54.420, C:33). One of the first trials to show benefit of endovascular thrombectomy in acute ischaemic stroke. Greatest clinical benefit of all trials because of the use of imaging techniques to select patients with the dual target of viable tissue and occluded major cerebral vessels. The findings have already changed clinical practice and appear in the European Stroke Organisation guidelines.
2. Davis SM, Donnan GA. Clinical practice. Secondary prevention after ischemic stroke or transient ischemic attack. New Engl J Med. 2012; 366(20):1914-22 (IF: 54.420, C: 12). This is an invited and widely cited authoritative review of secondary stroke prevention and brings together all the latest strategies for one of the most rapidly advancing areas of stroke medicine.
3. Parsons M, Spratt N, Bivard A ... Donnan G, Davis S, Levi C. A randomized trial of tenecteplase versus Alteplase for acute ischemic stroke. N Engl J Med 2012; 366(12):1099- 107 (IF: 54.420, C: 114). In this phase II trial with colleagues from Newcastle, we demonstrated that tenecteplase was superior to the currently used tPA for treatment of acute ischaemic stroke. If this is confirmed by the phase III trial which is underway, clinical practice will be changed and tenecteplase will become the routine thrombolytic agent of choice
4. Lees KR, Bluhmki, E, von Kummer R ... Davis SM, Donnan GA, Hacke W, NINDS, ECASS Atlantis. Time to treatment with intravenous Alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010; 375(9727):1695-703 (IF: 39.207, C: 672). This meta-analysis of trials of thrombolysis with tPA has been widely cited as a benchmark of clinical practice and evidence for guidelines around the world, defining the 4.5 hour time window.
5. Emberson J, Lees KR, Lyden P… Davis SM, Donnan GA et al. "Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with Alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials." Lancet 2014; 9958: 1929-1935. Davis and Donnan are active members of the thrombolysis pooling collaboration, focussed on precise delineation of the benefits and risks of intravenous tPA. (IF: 39.207, C:63)
6. Davis SM, and Donnan GA. The Wepfer Award Lecture in Nice. "Time Is Penumbra: Imaging, Selection and Outcome." Cerebrovasc Dis 2014; 38(1):59-72. Davis and Donnan are recognised world leaders in penumbral imaging and their work has altered clinical practice on an international level. (IF:3.698, C: 1)