Australasian COVID-19 Trial (ASCOT) update
Therapy drugs to treat people who contract COVID-19 continue to be a vital weapon in the fight against the pandemic, thanks to the world-leading Australasian COVID-19 Trial (ASCOT).
ASCOT is trialling various drug combinations on infected patients across 26 hospitals in Australia, New Zealand, India and Nepal, with support from funders including The Hospital Research Foundation.
Despite the increasing availability of vaccines, treatments are still needed, particularly with the challenges of vaccinating across many countries and the emergence of variants.
“COVID-19 will be with us for a long time still so it is crucial COVID-19 patients who are sick in hospital have clarity around the very best COVID-19 treatments that are available to them and that will work,” said ASCOT lead Associate Professor Steven Tong.
813 patients have so far been enrolled in ASCOT, with different antiviral, antibody and anticoagulation therapies being tested.
Thank you to all our Fund The Fight donors who supported this project! A more detailed update is as follows:
What are the latest treatments being investigated?
Antiviral Domain:
• Standard of care vs Nafamostat + Standard of care
• Approval to use the drug in Australia and NZ.
• 10 hospitals open to the Antiviral domain across Australia and NZ.
• Waiting for regulatory approval to use nafamostat in India. The Drug Controller General India (DCGI) is responsible for approving drugs for us in clinical trials in India. Delays have largely been due to a number of members of the DCGI falling ill or dying with COVID. Another submission has recently gone in so once approved we are hoping to start using nafamostat in India soon.
Antibody domain
• Hyperimmune globulin vs Standard of care.
• Hyperimmune globulin will only be available to sites in India.
• Convalescent plasma was dropped at the start of this year as it was shown in other trials that there was no benefit.
• The previous version of the protocol (ASCOT) included convalescent plasma vs standard of care. 33 patients were enrolled into ASCOT and we will be using this data to publish.
• Hyperimmune globulin has been submitted to the DCGI in India. Once this submission has been approved and contractual agreements with the drug manufacturer finalised, this domain will open in India.
Anticoagulation domain
Currently ASCOT ADAPT has three treatment arms in the anticoagulation domain:
• Standard dose heparin
• Intermediate dose heparin
• Standard dose heparin + aspirin
And we have recently added two additional arms:
• Intermediate dose heparin + aspirin
• Therapeutic (high) dose heparin
Two large trials (RECOVERY and REMAP-CAP) have recently decided to drop aspirin as it has shown no benefit. In tandem, the ASCOT ADAPT Data Safety Monitoring Board reviewed results from the first 300 patients enrolled into ASCOT ADAPT and agreed aspirin should also be dropped. For this reason we are now putting through an amendment to remove all treatment arms containing aspirin.
So in summary the following treatment arms will be tested in the Anticoagulation Domain:
• Standard dose heparin
• Intermediate dose heparin
• Therapeutic (high) dose heparin
There are about 200 patients who have already received standard dose heparin + aspirin. We will be using this data to publish outcomes from these patients.
Has ASCOT ADAPT informed any treatments so far?
We have not formally published any results yet as we are still accumulating data. We will be publishing results for the patients enrolled into the previous protocol (ASCOT) to help provide data on the efficacy of convalescent plasma. We also plan to publish results from ~200 patients enrolled into the treatment arms containing aspirin.
Why is ASCOT ADAPT different to other trials?
We are unique in the sense that we are testing treatments that are not being tested at this scale. We are the largest trial testing the effectiveness of nafamostat and various dosing of anticoagulants for patients who are hospitalised but not on mechanical ventilation (i.e. patients in the ‘moderate state’). There is also minimal data on the effectiveness of the hyperimmune product we will be using in the Antibody Domain.
In addition, ASCOT ADAPT is already set up to be adaptive, which means we can quickly amend the trial to introduce new emerging treatments that show potential to treat COVID-19.
Why is research into treatments still so important when we now have vaccines in the community?
There are a number of reasons why identifying effective treatments are still so important despite the development of a vaccine:
There are still people across the world, and in Australia currently, who are still not vaccinated. There will be a delay in vaccinating the larger community in a number of countries so we must be prepared to treat these patients. ASCOT ADAPT will help inform effectiveness of potential treatments.
Low to middle income countries are disproportionately impacted by COVID-19, and cheap, effective treatments are needed to treat patients in these countries.
We still see patients hospitalised with COVID-19 who have been vaccinated.
The development of variants means there is the possibility some vaccines will not be as effective against COVID-19 and we will see some vaccinated people in hospital with COVID-19.
When will you reach your target sample size?
As an adaptive trial and in the context of an ever-changing pandemic, it is difficult to predict recruitment rate. We are currently recruiting at a rate of 30 participants per week. This was about 50 per week when the wave peaked in India. This will increase again with the most recent outbreak in Australia. We hope to recruit 1200 patients by February 28th 2022, possibly 1500 by middle of next year.
Thank you to our funders
Thank you for helping to contribute to research that will change people’s lives. COVID-19 has had far reaching impacts across the world on an economic and social scale, particularly in low to middle income countries. COVID-19 will be with us for a long time still so it is crucial COVID-19 patients who are sick in hospital need clarity around the very best COVID-19 treatments that are available to them and that will work.
