Gold standard trial finds remdesivir shortens duration of COVID-19

Remdesivir is superior to placebo in shortening the time to recovery in adults hospitalised with COVID-19 with evidence of lower respiratory tract infection.
 
These are the findings of the final report on the use of remdesivir as a treatment for COVID-19, published on 8 October in The New England Journal of Medicine.
 
The double-blinded, randomised, placebo-controlled trial, known as the Adaptive COVID-19 Treatment Trial (ACTT), involved 1062 patients.
 
Of those, 541 were randomly assigned to receive remdesivir (200 mg loading dose on day one, followed by 100 mg daily for up to nine additional days), while 521 patients received a placebo for up to 10 days.
 
Those who received remdesivir had a median recovery time of 10 days, as compared with 15 days among those who received the placebo.
 
Remdesivir also had an effect on mortality, though these results were not statistically significant.
 
The Kaplan–Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15, and 11.4% with remdesivir and 15.2% with placebo by day 29.
 
Meanwhile, serious adverse events were reported in 24.6% of patients who received remdesivir and 31.6% of those who received the placebo.
 
Preliminary results from the trial were published on 29 April.
 
Royal Melbourne Hospital infectious diseases clinician Associate Professor Steven Tong is the principal investigator for the AustralaSian COVID-19 Trial (ASCOT) and a co-lead of clinical research at the Doherty Institute.
 
He told newsGP he was not surprised by the results of this final report.
 
‘These [findings] really confirm what we’ve known before,’ he said.
 
‘The authors have published their preliminary report prior to this, and this is the final report which confirms that there’s a shortened time to clinical improvement for the patients who receive remdesivir.’
 
Associate Professor Louis Irving, Director of Respiratory and Sleep Medicine at the Royal Melbourne Hospital, agrees these findings are not surprising.
 
However, he told newsGP he was pleased with the results because they are in line with his experiences treating Australian patients with COVID-19-related pneumonitis.
 
Associate Professor Irving says his hospital used remdesivir when treating approximately 46 patients with COVID-19 with evidence of lower respiratory tract infection.
 
‘Our experience was positive,’ he said.
 
‘We weren’t doing a trial, but we used it in people as soon as they looked as though they needed supplemental oxygen. In other words, as soon as there was good evidence of a lower respiratory infection.’
 
Associate Professor Tong says the study found this was the group that benefited most from treatment with remdesivir in the ACTT trial.
 
‘Whereas there was no benefit in those who were already on high-flow nasal oxygen or non-invasive mechanical ventilation or on a ventilator,’ he said.
 
Associate Professor Tong says there was also ‘not much benefit’ for patients who were not receiving oxygen at all.
 
The results of the trial did not find evidence for the use of remdesivir in the absence of a lower respiratory tract infection, Associate Professor Irving says, and he cannot speculate on whether it may be beneficial in such cases.
 
‘I think it’s unproven what its benefit would be with an upper respiratory infection,’ he said. ‘It’s not clear.
 
‘The trial suggests that the best action was for people who were exhibiting some evidence of lower respiratory infection, and we used [the] need for supplemental oxygen as evidence of that.’


Associate Professor Steven Tong says the results of this study confirm what clinicians ‘largely already knew’ regarding the use of remdesivir.

Associate Professor Irving says that, at his hospital, remdesivir was used in conjunction with steroid treatment.
 
‘That was the other “at the time” drug that appeared to have a benefit,’ he said.
 
‘Remdesivir appeared to shorten the duration of the illness and works as an antiviral agent, and steroids appear to have a mortality benefit and work presumably to subdue untoward immune responses,’ he said.
 
On the whole, Associate Professor Irving says remdesivir was well tolerated.
 
‘I think we only had to stop using it in one or two [patients] because of a five-fold increase in abnormal liver function [with a hepatitic picture],’ he said.
 
‘That was the main side effect that we looked out for.’
 
Associate Professor Irving says there also ‘might have been a couple’ of patients who were not able to receive remdesivir in the first place, as they already had abnormal liver function.
 
He points out there was no problem accessing supply of the drug at the time, and says supply is not currently an issue.
 
Remdesivir is a nucleoside analogue prodrug that has inhibitory effects on pathogenic animal and human coronaviruses, including SARS-CoV-2 in vitro, and was originally developed to treat Ebola.
 
On 1 May, it became  the first therapy to receive approval by the US Food and Drug Administration for emergency use for COVID-19. In October, it became the first medication recommended in Australia by the National COVID-19 Clinical Evidence Taskforce as a considered treatment for COVID-19 to aid recovery time.
 
Associate Professor Irving says the final report of this research further validates the current use of remdesivir, saying it is on par with the use of steroids for treating pneumonitis-related COVID-19.
 
‘I think most people would see remdesivir as one of the two most effective drugs we have at the moment for treating people who appear to be developing severe COVID,’ he said.
 
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