Triple Therapy Prevention Of Recurrent Intracerebral Disease EveNts Trial (TRIDENT)
Funder
National Health and Medical Research Council
Funding Amount
$5,256,292.00
Summary
Acute intracerebral haemorrhage (ICH) is a serious form of stroke. Survivors of ICH are at high risk of repeat events. Blood pressure lowering is a very important to prevent repeat events but data shows blood pressure is poorly controlled in these patients. In this research we investigate whether an approach that uses a 'triple pill' strategy (3 low dose BP drugs in one pill) in ICH patients with mild to moderate hypertension can decrease major cardiovascular events.
IMPROVING STROKE OUTCOMES: NEW TARGETS AND THERAPIES
Funder
National Health and Medical Research Council
Funding Amount
$7,212,064.00
Summary
Previously we established a unique collaboration of researchers from the basic and clinical sciences.. The main aim of this ' vertically integrated ' model was to develop new therapies to improve stroke outcomes. We developed a system to identify ' off-the-shelf ' compounds which protect the brain after stroke onset. This involves data assimilation (meta-analysis) in a unique way, an approach which has attracted attention internationally. We are also completing an important clinical trial using ....Previously we established a unique collaboration of researchers from the basic and clinical sciences.. The main aim of this ' vertically integrated ' model was to develop new therapies to improve stroke outcomes. We developed a system to identify ' off-the-shelf ' compounds which protect the brain after stroke onset. This involves data assimilation (meta-analysis) in a unique way, an approach which has attracted attention internationally. We are also completing an important clinical trial using the clot dissolving agent tPA to extend the time during which the drug may be effective beyond the three-hours currently used. In the next phase of our program we plan to expand the basic science component to identify parts of brain cells (axons and dendrites) which may yield important information about new drugs to protect the brain. We will use our novel summary data technique to test drugs in animal models more appropriate to the human stroke paradigm than have been used in the past In clinical studies we will follow our theme of identifying new targets for therapy using sophisticated PET and MRI imaging techniques, both in patients who are at great risk of stroke recurrence after a minor warning stroke and those with stroke caused by bleeding within the brain. These studies will provide information about predictors of recurrent and worsening stroke which may be modified by new therapies. The final stage in identifying new therapies is the Phase III clinical trial. We will complete one of these in which the most appropriate drug preventing further strokes in a major new stroke subtype will be identified. Toward the end of the program, we will commence phase 3 studies of drugs we have selected as being most likely to protect the brain based on our animal experiments. The main benefit of this unique collaborative research model is to efficiently identify new therapies to reduce the burden of stroke, currently the second most common cause of death globally.Read moreRead less
Shared Team Approach Between Nurses And Doctors For Improved Risk Factor Management (STAND FIRM)
Funder
National Health and Medical Research Council
Funding Amount
$1,945,676.00
Summary
There are many proven treatments for preventing people with stroke from having a recurrent event, e.g. maintaining blood pressure at acceptable levels. However, uptake of therapies is poor. We will assess whether patients receiving individualised management plans, prepared and administered by both doctors and nurses will have risk factors controlled better than those receiving usual care. The plan includes education of patients to help them have more control over their own care.
The outcomes to be assessed are recurrent ischaemic stroke, intracranial haemorrhage, myocardial infarction, parenchymal embolism and vascular death. Should these outcomes be significantly reduced, the public health and economic issues which will be addressed in this study are considerable. Approximately 40,000 new and recurrent cases of stroke occur in Australia each year, and about 80% of these are ischaemic. There is an average prevalence of about 20% of large or complex aortic plaque among p ....The outcomes to be assessed are recurrent ischaemic stroke, intracranial haemorrhage, myocardial infarction, parenchymal embolism and vascular death. Should these outcomes be significantly reduced, the public health and economic issues which will be addressed in this study are considerable. Approximately 40,000 new and recurrent cases of stroke occur in Australia each year, and about 80% of these are ischaemic. There is an average prevalence of about 20% of large or complex aortic plaque among patients with ischaemic stroke. About the same proportion of cases of ischaemic stroke yearly are associated with the presence of complex aortic plaque alone, and as many again with simple plaque (40% in total). Using the NHMRC estimated cost of $40,000 per stroke (and assuming that recurrent stroke costs are similar to initial stroke costs) and the estimated recurrent stroke rates of 11.9-100 person-years for plaque > 4 mm, the national cost of recurrent ischaemic stroke attributable to complex aortic plaque alone is about $3 million in the first year. This estimate does not include patients with incident TIA and atherosclerotic plaque or the resources spent on evaluating recurrent stroke and TIA attributable to aortic plaque, the cost of lost wages, or the negative impact on the quality of life of the victims. The economic and public health burden to our society could be greatly reduced by successful efforts at secondary stroke prevention in individuals with aortic plaque and TIA or ischaemic stroke. If just 25% of recurrent ischaemic strokes associated with aortic arch debris could be prevented by treatment interventions, the annual savings to society for recurrent ischaemic stroke alone would be considerable.Read moreRead less
Contribution Of Ovarian Cancer Stem Cells To Chemoresistance And Recurrent Disease.
Funder
National Health and Medical Research Council
Funding Amount
$378,940.00
Summary
Ovarian cancer is the most lethal gynaecological cancer. Previously, we showed that cancer stem cells are the “beating heart” of the ovarian cancer and are responsible for drug resistance and tumour relapse. The ineffective targeting of these cells by chemotherapy is accountable for the poor clinical outcomes in ovarian cancer patients. This project will define the molecular signals involved in maintenance of cancer stem cells and develop targeted therapies against these cells.
Antiphospholipid Antibodies, Beta 2-Glycoprotein I And Control Of Coagulation.
Funder
National Health and Medical Research Council
Funding Amount
$471,000.00
Summary
Antiphospholipid antibodies are associated with an autoimmune condition characterised by the presence of clots and recurrent miscarriages. Although the name implies that the antibodies bind phospholipid the disorder is characterised by circulating antibodies which bind a protein in the blood known as Beta 2-Glycoprotein I. The exact role of Beta 2-GPI in the body has not been determined, although there are numerous studies looking at this protein. This protein has been thought to be important in ....Antiphospholipid antibodies are associated with an autoimmune condition characterised by the presence of clots and recurrent miscarriages. Although the name implies that the antibodies bind phospholipid the disorder is characterised by circulating antibodies which bind a protein in the blood known as Beta 2-Glycoprotein I. The exact role of Beta 2-GPI in the body has not been determined, although there are numerous studies looking at this protein. This protein has been thought to be important in controlling the clotting system in humans and other mammals. The evidence for this has been contradictory, however, we have recently made a major new finding on the function of this protein on the clotting system. We will be using sophisticated molecular biology techniques to further characterise the role that Beta 2-GPI has in controlling clotting factors in the body. We have been able to eliminate the gene for Beta 2-GPI in mice thus deriving mice that do not produce any Beta 2-GPI protein. These mice are called Beta 2-GPI knockout mice and will be an ideal animal model to examine the function of Beta 2-GPI and its new role in controlling the clotting cascade by targetting a specific part of this pathway. In addition, these findings may be able to provide new information on how Beta 2-GPI controls clotting factors and the effect of antiphospholipid antibodies on this system, which may lead to new treatments for antiphospholipid antibodies and more generally clotting disorders.Read moreRead less
Stroke outcomes directly relate to brain tissue rescue. We have contributed to changes in clinical practice through many clinical trials of new protocols and therapeutic strategies. Our program will focus on brain salvage in the pre-hospital setting and the acute hospital environment. We will use novel approaches to enhance brain recovery and design new implementation strategies to maximise the benefits of these therapeutic advances.
I am a practising hospital neurologist and world leader in the prevention and treatment of stroke. Our research aims to realise exciting new break-throughs for stroke sufferers by testing the effectiveness and safety of new treatments that promise to improve recovery of function of damaged brain and reduce disability after stroke, and to prevent recurrent strokes.