Impact of VT
Venous thromboembolism (VT) is a blood clot that starts in a vein. There are 2 types:
- deep vein thrombosis – a clot in a deep vein, usually the leg
- pulmonary embolism – a clot that breaks free from a vein wall, travels to the lungs and blocks some or all blood supply.
VT carries a high risk of severe health effects or death. More than 17,000 Australians every year will have an embolism, and the incidence is increasing as our population ages. Groups at higher risk of VT are older people, people who have cancer, and people who are immobilised (for example, hospitalised).
VT treatment and the trial
Health care workers treat thromboembolism with blood thinning agents. These reduce the chance of a clot recurring, but Dr Vivien Chen explains the treatment is not without risks.
‘Blood thinning agents reduce the chance of clotting, but they can also increase the chances of bleeding,’ she says.
‘If a bleed occurs in the brain or gut it can cause major problems. Apart from affecting the health of the patient, it also affects the health budget, because the cost of treating such complications is high.’
In 2019, the treatment guidelines changed from the standard drug, warfarin, to 2 new agents – rivaroxaban and apixaban.
‘Both are as effective as warfarin,’ Dr Chen says. ‘But which is better? There has never been a head-to-head trial of the 2 agents, so we don’t have clear clinical guidelines for treatment.’
‘The COBRRA trial is the comparison of bleeding risk between rivaroxaban and apixaban for the treatment of acute venous thromboembolism. It will tell us which is better for our patients in the long term. The main measure we will use is which agent results in fewer bleeds for patients.’
The randomised controlled trial is an international effort. The Canadian Institutes of Health Research Funding is funding the trial in Canada. The MRFF is funding the trial in Australia and New Zealand. The Australia/New Zealand arm of the trial will have one-quarter of the international total of 2760 patients.
Added value for Australia
‘There is enormous value-add to Australia’s involvement, because the COBRRA trial will be the base for 2 additional investigations,’ she explains.
The first is on health economics, using local data to conduct an Australian cost analysis.
’Getting evidence about which treatment is most cost-effective in the long term can help us to design the most cost-effective intervention.
‘This doesn’t necessarily mean choosing the cheaper drug. The analysis will take into account both the cost over time and the potential savings by preventing major complications. The more expensive treatment could be more cost effective if it reduces the need for treatment of complications.’
The ANZAC Research Institute will conduct a second investigation on biomarkers.
‘We know statistically that someone who has a blood clot has a 10% chance of getting another within a year,’ Dr Chen says. ‘They’ll have a 30% chance of another in 3 to 5 years.’
‘But these are just averages. Some individuals seem to have a higher or lower risk. If we can identify biomarkers that tell us someone’s risk of a second clot, we can better individualise treatment.
‘For example, if someone has a low chance of a second clot but a high chance of bleeding, we may not want to increase the bleeding risk by prescribing a blood thinner over the long term.’
Dr Chen is excited that the MRFF funding has enabled Australia’s involvement in this international project.
The funding for this trial has brought together 2 national clinical trial collaborative groups:
- the Thrombosis and Haemostasis Society of Australia and New Zealand – Clinical Trial Group (THANZ-CTG), and
- the Canadian Venous Thromboembolism Clinical Trial Research Network (CanVECTOR).
They will also work together with the University of Sydney NHMRC Clinical Trial Centre, and ANZAC Research Institute.
‘The collaboration structure formed to facilitate COBRRA may become a platform for ongoing trials. Dr Chen says. ‘Other international investigations are already including us in their conversations.’