Implementation Of Quality Use Of Advanced CT Imaging In Acute Stroke
Funder
National Health and Medical Research Council
Funding Amount
$1,128,594.00
Summary
Many centres now use advanced CT scanning techniques to assess stroke patient suitability for clot-dissolving treatment. However, there is major variation across Australia in the clinical application of advanced CT scanning techniques, which is a barrier to the delivery of this treatment. This project addresses the variation in CT imaging techniques by developing, piloting and evaluating the implementation of a standardised advanced CT scanning strategy for acute stroke patients.
Tenecteplase Versus Alteplase For Stroke Thrombolysis Evaluation (TASTE) Trial
Funder
National Health and Medical Research Council
Funding Amount
$4,180,030.00
Summary
Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation (TASTE) is an Australian-led international randomised trial designed to generate practice-changing evidence by translating the advanced imaging treatment selection approach used in our previous pilot studies. TASTE aims to confirm the superiority of the new-generation clot-dissolving agent, tenecteplase, over the standard agent, alteplase, in the broad group of stroke patients eligible for acute clot-dissolving treatment.
Acute Stroke: Imaging The Ischaemic Penumbra With Perfusion CT
Funder
National Health and Medical Research Council
Funding Amount
$243,000.00
Summary
The burden of stroke is large. Clot-dissolving medication (thrombolysis) may dramatically improve the outcome of many patients with severe stroke by unblocking the affected brain artery. However, very few patients receive this medication, as the current approval is restricted to treatment within 3 hours of stroke onset. The major aim of thrombolysis is to rescue brain tissue with reduced blood flow (the ischaemic penumbra) from becoming irreversibly damaged (infarcted). The penumbra progressivel ....The burden of stroke is large. Clot-dissolving medication (thrombolysis) may dramatically improve the outcome of many patients with severe stroke by unblocking the affected brain artery. However, very few patients receive this medication, as the current approval is restricted to treatment within 3 hours of stroke onset. The major aim of thrombolysis is to rescue brain tissue with reduced blood flow (the ischaemic penumbra) from becoming irreversibly damaged (infarcted). The penumbra progressively becomes infarcted over the next 48 hours if blood flow is not restored by the blood clot in the brain artery being dissolved. Penumbral brain tissue cannot be identified with clinical assessment or standard CT scanning. New generation CT scanners are capable of assessing brain blood flow. Perfusion CT imaging (CTP) is well tolerated and time-efficient, and can be integrated into the brain CT scanning process performed on all stroke patients. Preliminary evidence suggests that CTP can distinguish between tissue that represents the ischaemic penumbra, and tissue that is already permanently injured. This project aims to validate the use of CTP in imaging the ischaemic penumbra. This will be based on testing the accuracy of CTP tissue signatures of the penumbra in predicting clinical outcome and final stroke size. This is the only national collaborative study planned worldwide for this relatively new but increasingly accessible imaging technique. The ability to rapidly identify under-perfused but still viable brain with CTP would add new and exciting management options to the routine emergency assessment of stroke patients. The results of this unique study could have a significant impact on the management of acute stroke worldwide. If validated, it is anticipated that CTP would be widely used to improve patient selection for stroke thrombolysis, especially in safely extending the time window so that a greater number of patients can be treated with better outcomes.Read moreRead less
Improving Stroke Outcomes: Attenuating Progression And Recurrence
Funder
National Health and Medical Research Council
Funding Amount
$9,331,996.00
Summary
Stroke is the second most common cause of death and major cause disability. There are few proven interventions, so we need to introduce new ones. We developed a bench to bedside program to introduce new stroke therapies and its early secondary prevention. Our general goal is to provide evidence for their effectiveness and safety. We will use animal stroke models, markers in the blood to help diagnose and predict stroke outcome and imaging to help select patients for several clinical trials.
Low-Dose Tenecteplase Vs Standard-Dose Alteplase For Acute Ischaemic Stroke: An Imaging Based Safety And Efficacy Study
Funder
National Health and Medical Research Council
Funding Amount
$349,281.00
Summary
This study compares standard dose alteplase (a proven stroke thrombolytic) with a low dose of the new medication tenecteplase for stroke treatment. We propose that the clot-dissolving activity of low-dose tenecteplase will be superior to alteplase, with a lower risk of brain bleeding. MRI scanning is the most effective way of assessing outcomes and will be used to measure how well the medication restores blood flow, the amount of permanent brain damage, and whether any brain bleeding occurs.
To Determine The Means By Which Plasminogen Activators Modulate Integrity Of The Blood Brain Barrier
Funder
National Health and Medical Research Council
Funding Amount
$523,084.00
Summary
Tissue-type plasminogen activator (t-PA) is used clinically to remove blood clots. However, t-PA can also cause brain injury and influence the blood brain barrier (BBB) which has implications for the treatment of patients with ischaemic stroke. This project will use in vitro and in vivo models to understand the mechanism by which t-PA modulates the BBB. A novel tPA variant will also be created that ultimately may be of benefit for patients with ischaemic stroke.
To Investigate How The Aggregation Of Proteins During Neuronal Injury Promotes Neurotoxic Plasmin Formation
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
tPA is an enzyme given to patients to remove stroke-causing blood clots but can have harmful effects in the brain. tPA needs a cofactor to function optimally. In the blood, this cofactor is fibrin. However the cofactor that allows tPA to function in the brain is unknown. This project explores a novel cofactor for tPA in the injured brain. We will attempt to block this harmful cofactor in the brain while still allowing tPA to remove clots thereby improving stroke outcome.
The Adverse Effects Of Diabetes On Stroke: An Echoplanar MRI Study
Funder
National Health and Medical Research Council
Funding Amount
$278,418.00
Summary
Stroke is the most common, major brain disease in Australia. It is the third most common cause of death and the most common cause of adult disability. There is a close link between diabetes and stroke. Firstly, diabetes is an important risk factor for the development of stroke. Secondly, about one third of stroke patients have diabetes. In general, their outcome is much worse than other patients. In fact little is known about the cause of this adverse effect in stroke patients and there is uncer ....Stroke is the most common, major brain disease in Australia. It is the third most common cause of death and the most common cause of adult disability. There is a close link between diabetes and stroke. Firstly, diabetes is an important risk factor for the development of stroke. Secondly, about one third of stroke patients have diabetes. In general, their outcome is much worse than other patients. In fact little is known about the cause of this adverse effect in stroke patients and there is uncertainty whether intensive control of blood sugar in acute stroke improves outcome. Our pilot work suggests that raised brain lactate, together with larger stroke size, might together be responsible for the worse outcome in diabetic patients. We can now measure brain lactate and stroke size with new MRI techniques called echoplanar MRI, which can allow measurements of brain chemistry, blood flow, potentially viable and dead tissue. A new monitoring device allows non-invasive measurement of blood sugar every 5 minutes. Using these strategies, we are planning a comprehensive study of the causes of the worse stroke outcome with diabetes. In addition, we are incorporating a study to determine whether intensive control of blood sugar in the first 3 days after stroke, compared with standard treatment, reduces brain lactate and growth of the actual stroke. An understanding of these effects will have important implications for the acute treatment of stroke patients. If we can show that rigorous control of blood sugar reduces brain lactate and stroke growth, our study will lay the ground work for a large clinical trial. This could have important implications, both in Australia, and overseas.Read moreRead less
Targeting Necroptosis Signalling To Counter Stroke-induced Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$605,809.00
Summary
The origins of the brain injury that arises from stroke remain a matter of enormous interest. Our work suggests that a poorly understood form of cell death, termed necroptosis, contributes to injury to the brain following stroke. In addition to developing an advanced understanding of this process, we will use drugs developed at the Walter and Eliza Hall Institute to test whether blocking this process might be a plausible therapeutic strategy in stroke patients.
Discovery To Therapy Implementation In Acute Stroke
Funder
National Health and Medical Research Council
Funding Amount
$585,269.00
Summary
Advances in acute stroke therapies are occurring rapidly but challenges remain in their safe and effective delivery to stroke sufferers. This research focuses on testing a potentially superior ‘clot busting’ drug therapy for acute stroke and on identifying reasons why one of the most widely used current therapies carries a risk of significant harm due to bleeding into the brain. The work also investigates how to better implement the newest form of acute therapy, mechanical blood clot extraction.