Australian hydroxychloroquine trial to continue despite WHO ‘pause’

The World Health Organization (WHO) Director-General Dr Tedros Adhanom Ghebreyesus said the decision to ‘pause’ the use of hydroxychloroquine in its global Solidarity Trial is precautionary and based on a Lancet study that showed coronavirus patients taking the drug were at higher risk of death and heart problems than those who were not.
 
The announcement has reportedly led to urgent talks among researchers leading the Australasian COVID-19 Trial (ASCOT) on whether to continue testing hydroxychloroquine as a treatment for coronavirus patients, but a separate trial focused on high-risk healthcare workers is set to continue.
 
The COVID-SHIELD study, the first to test the antiviral as a preventive measure against COVID-19, only began recruiting last week, but lead investigator Professor Ian Wicks told newsGP the researchers are set to push ahead despite the WHO’s announcement.
 
‘We don’t think it fundamentally changes anything that we were planning to do … [the Lancet] study is quite different to ours in a few respects,’ he said.
 
‘Even the authors sounded a note of caution about the design of the study and pointed out that randomised controlled trials were necessary to draw a firm conclusion, and that their study had no implications for preventive prophylactic trials.’
 
Professor Wicks said the ‘real-world observational’ Lancet study focused on treatment and did not control for varying underlying health issues or differences in drug dosages or combinations, whereas COVID-SHIELD will be a ‘gold standard’ randomised controlled trial of the potential use of hydroxychloroquine as a prophylactic.
 
‘We’re trying to find something that might add some extra protection for healthcare workers on the frontline and that remains our primary goal,’ he said.
 
‘All participants are going to be carefully screened for any cardiac problems that might predispose them to cardiotoxicity … [so] we’ll be monitoring for that, along with any new symptoms.
 
‘While we obviously all have to take new information as it arises onboard, we think there are good reasons to separate what we’re doing from what’s being reported.
 
‘It’s a very powerful gold standard trial design and it’s in a fundamentally different group.’
 
The COVID-SHIELD trial is still in its recruitment phase, which began at Royal Melbourne Hospital last week, and participants are expected to start receiving either the drug or a placebo in coming weeks.
 
Even though case numbers in Australia have reduced considerably since the trial was first conceived, Professor Wicks said the planned easing of social distancing measures could mean further clusters and outbreaks, if not a second wave.
 
‘While we all hope that that doesn’t occur, we think the trial will be quite well timed to pick up that next phase,’ he said
 
‘It’s increasingly clear that it only takes one person coming in to emergency or getting admitted with atypical symptoms [to get an outbreak]. This is a highly contagious virus that can quickly spread.
 
‘In spite of our great track record … it’s highly likely that patients will slip through the cracks and still pose a threat to the people looking after them.’
 
Somewhat complicating the issue is the widespread promotion of hydroxychloroquine as a potential ‘cure’ for coronavirus, which has led to warnings from medical bodies such as the RACGP and the National COVID-19 Clinical Evidence Taskforce against ‘off label’ use of the drug.
 
Professor Wicks said he ‘totally supports’ concerns about non-evidence-based use of hydroxychloroquine, but is hopeful COVID-SHIELD will provide certainty around its potential to protect against the coronavirus.
 
‘We would certainly agree with all the caution that has been articulated around using this outside of a properly conducted clinical trial,’ he said.
 
‘This idea came in-part out of our experience in rheumatology of widely prescribing hydroxychloroquine for its preventive value against flare ups in diseases like lupus and rheumatoid arthritis, where we use it very routinely and are pretty comfortable with its side effect profile in that group.
 
‘That combined with the evidence from in vitro studies where it has an anti-viral effect on coronavirus, led us down this path … we felt obliged to pursue it as a possibility that might offer an extra degree of protection in healthcare workers in particular.
 
‘We’re trying to produce gold standard scientific evidence for efficacy, one way or another.
 
‘If the trial’s negative, hopefully it will put the issue to bed.’
 
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