The results of early studies from the US and China, which show disappointing results in the use of an antimalarial drug and an anti-retroviral drug in treating Covid-19, will not impact trials of the drug under way in Australia, researchers say.
To date more than 300 clinical trials in humans are under way around the world to investigate treatments for the virus, with several of these occurring in Australia. Among the most hyped drugs are hydroxychloroquine, an antimalarial which is also used to treat people with painful autoimmune conditions, and lopinavir and ritonavir, both antiretroviral drugs. Antibiotics are also being studied.
But a study of Covid-19 hospital patients given hydroxychloroquine in the US found no benefit from the drug, either alone or given in combination with an antibiotic. In fact, the patients treated with hydroxychloroquine alone had a higher mortality rate. Meanwhile, researchers in China found that neither lopinavir or ritonavir showed any benefit in patients admitted to hospital with mild-to-moderate cases of the disease.
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‘A lot still to learn’
The findings come as all patients with Covid-19 being admitted to intensive care at the Royal Brisbane and Women’s hospital in Queensland are being given hydroxychloroquine as part of their treatment. Neither the Queensland department of health nor the hospital responded to multiple requests for comment from Guardian Australia as to whether the trial would be reassessed in light of evidence from China.
A separate study, known as Ascot (AustralaSian COVID-19 Trial), is under way in more than 70 Australian hospitals and will test whether lopinavir/ritonavir and hydroxychloroquine, alone or in combination, prevents deterioration of Covid-19 patients. A leader of the Ascot study, Prof David Paterson, said despite the disappointing findings from the US, the Australian study would go ahead. The US study was retrospective and conducted in a relatively small group of patients, whereas the Ascot study is being conducted as a randomised control trial, the strongest type of study and the gold standard for evidence.
“The conclusions of the authors of the US study were that randomised trials are needed,” Paterson said. “This is exactly what we are undertaking with Ascot. Many commentators have observed that the US study was observational in design, and that it may have been that people who were not very sick were given no treatment and therefore had a greater chance of surviving, while those who were very sick and were at a greater intrinsic chance of dying were given hydroxychloroquine or other treatments in desperation.
“There is clearly a lot still to learn about treatments for Covid-19. Large randomised clinical trials like Ascot are the only way to do this.”
A federal Department of Health spokesman said the government was closely monitoring the results of studies from around the world investigating treatment or preventions for Covid-19.
“The clinical evidence base is currently limited and results from large, prospective and controlled studies are required before the efficacy and safety of hydroxychloroquine is better understood,” he said. “Clinical trials in Australia are conducted by a sponsor who has overall responsibility for the trial, with oversight by a human research ethics committee. Within the bounds of a clinical trial, safety is carefully monitored and the sponsor and committee can halt a trial at any time should serious safety issues emerge.”
‘Panic causing bad decisions’
However, despite advice from the Australian Health Protection Principal Committee that experimental use of medications is not recommended for Covid-19, and should only be prescribed as part of a clinical trial, some hospitals around Australia are giving the drugs to critically unwell patients outside of trials. This differs from advice from the drugs regulator, the Therapeutic Goods Administration, that the drugs can be given as part of clinical trials or to severely unwell Covid-19 patients.
Infectious diseases physician and former adviser to the World Health Organization, Prof Peter Collignon, said this was concerning.
“I think this is an indication of panic causing bad decisions,” he said.
“Even in the face of evidence showing it’s doing no good we continue to use these drugs. Of course, doctors are able to use drugs off-label. But if it’s clearly shown – and I think the evidence is showing this for hydroxychloroquine – that it’s doing more harm, then it should be unethical to give patients these drugs outside of a trial.”
He added that ethics committees should be constantly reviewing approvals of clinical trials as evidence emerges.
Dr Gaetan Burgio, an Australian National University infectious disease specialist , said given the lack of proven efficacy and the potential serious toxicity on seriously unwell patients, he also believes hydroxychloroquine should not be administered to patients outside of clinical trials.
However, he said there was no reason to stop Australian clinical trials as a result of the findings from overseas so far. “In my view, as the patients are a well controlled clinical setting and thoroughly monitored, there is no reason to halt them.”
Maintaining scientific standards
Australian states and territories have differed in their approach to off-label use of drugs to treat Covid-19. In Western Australia and Victoria, there is no off-label or experimental use of medications for patients outside of clinical trials. The Queensland department of health said chloroquine, hydroxychloroquine and lopinavir-ritonavir have been used on selected patients across Queensland, but did not confirm whether these patients were part of clinical trials. NSW Health did not respond to a request for comment.
The proliferation of studies examining treatments for Covid-19 prompted bioethicists Dr Jonathan Kimmelman and Prof Alex John London to write, in the international journal Science, that crises “are no excuse for lowering scientific standards”. They wrote that regulatory agencies “should also avoid making public recommendations or granting emergency use authorisation for interventions whose clinical merits remain to be established and, instead, present clinical trials as a mechanism for addressing uncertainty without compromising patient interests”.
On Monday, the Medical Journal of Australia published a piece summarising randomised trials under way to treat Covid-19. Led by the Menzies School of Health Research, it said “the near-instant dissemination of information and opinion that is prevalent in today’s world makes properly designed clinical trials more important than ever”.
Currently, there are no approved treatments for Covid-19. Patients are given supportive care, for example ventilation, if breathing significantly deteriorates.