ASCOT is a clinical trial that will generate clinical evidence about treatment for COVID-19 that can be applied during the pandemic to reduce mortality or the need for mechanical ventilation in hospitalised but not yet critically ill patients with COVID-19.
The trial aims to generate results quickly. After the trial begins, results will be continually analysed, so that ineffective therapies can be stopped, and new therapies can be evaluated as part of the trial.
The SARS-CoV-2 virus causes the disease COVID-19. The number of people infected is rapidly increasing and many are needing hospitalisation, some require mechanical assistance with breathing (mechanical ventilation). The case fatality rate in Australia has been 2.4%. Few therapeutics have been shown to be of benefit in treating COVID-19, and providing patients supportive care – providing oxygen, treating other medical conditions, and mechanical ventilation when needed, is currently a key part of treating COVID-19. Dexamethasone, a steroid medication, Tocilizumab, a targeted anti-inflammatory drug, and an antiviral medication called Remdesivir, have been demonstrated to be beneficial for some patients.
The trial will investigate different types of treatments:
- Antiviral therapies – which aim to limit the virus replicating
- Therapeutic antibody treatment – which aim to fight the virus
- Anticoagulation therapies – which aim to reduce the risk of blood clots associated with COVID-19 infection
The Need To Test In Clinical Trials
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At this stage, there are few specific therapies that have been shown to improve clinical outcomes in patients with COVID-19. By clinical outcomes we mean things like dying, or requiring mechanical ventilation, or the length of hospitalisation. Things that matter to patients.
Promising therapies in the laboratory do not always translate to improved clinical outcomes.
There are many examples of this in cancer therapies but also antiviral therapies like those that will be tested in the trial. Promising therapies may actually be harmful in some cases.
The best way to determine whether a promising therapy actually improves clinical outcomes is to perform a clinical trial. In a clinical trial, patients are randomly allocated to different therapies (in some case to no specific therapy – this is the standard of care). We can then objectively assess whether patients who received a specific therapy fare better, worse or the same compared to patients who received a different therapy or standard of care. This is the most rigorous way to demonstrate the benefits or harms of therapies.
ASCOT is a type of clinical trial known as an Adaptive Platform Trial (APT).
APTs are designed to be able to study multiple interventions in a disease or condition, by adding and removing treatment interventions to the trial, using a predefined decision algorithm.
In APTs, treatments that are shown to be better than the current standard treatment already available can then become the standard treatment, and other new treatments can be added to the study. This means that APTs can continue to enrol participants as new research questions arise, and as new treatments become available.
APTs can also use other ways to increase the study efficiency, leading to faster results. In a traditional RCT, participants will be put into groups of the same size, and there is an equal chance of being allocated to each group (50% chance of being in a group). APTs, however, can change the size of the groups, if the results from the timepoints show that one treatment may be more effective than another, by changing the odds of being assigned to each group (for example, 70% chance of being in one group, 30% chance of being in another group).
This means that more patients can be put in the group that may be more effective, and less participants will be put into the group that may not be as effective. It also means that if a treatment seems to not be working or seems to be causing harm, that treatment can be stopped and removed from the study.