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COVID-19 guidelines update on remdesivir, VTE prophylaxis

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The National COVID-19 Clinical Evidence Taskforce (the taskforce) has updated its evidence base on antivirals and other disease-modifying treatments, including a recommendation specific to remdesivir.
 
Following a review of a randomised trial of the drug, published in The Lancet on 29 April, experts have recommended that at this stage remdesivir should only be administered in the context of randomised trials with appropriate ethical approval.
 
Taskforce Chair Associate Professor Julian Elliott acknowledged the preliminary results for the Adaptive COVID-19 Treatment Trial (ACTT), but said they will be holding off from incorporating any results into the guidelines until the trial is finalised.
 
‘We are running evidence surveillance every day, picking up any new information, and that’s fed through to our panels every week, going through the full, rigorous, high-quality guideline process with weekly updates, which is completely novel,’ he told newsGP.
 
‘Based on the information we have, the panels are quite clear and have reaffirmed that there’s insufficient data to recommend the use of remdesivir outside of a clinical trial.’
 
That is also the recommendation for antivirals, including hydroxychloroquine and lopinavir-ritonavir.
 
Meanwhile, emerging observational data has indicated a high incidence of venous thromboembolism (VTE) among confirmed cases of COVID-19, including pulmonary embolism and deep vein thrombosis.
 
The taskforce has added a recommendation for the use of VTE prophylaxis in people with moderate COVID-19.
 
Experts recommend the use of prophylactic doses of anticoagulants, preferably low-molecular-weight heparin (LMWH) (eg enoxaparin 40 mg once daily or dalteparin 5000 IU once daily) in adults with moderate COVID-19 or other indications, unless there is a contraindication such as risk for major bleeding.
 
Where severe acute kidney disease is present, unfractionated heparin or renally adjusted doses of LMWH may be used (eg enoxaparin 20 mg once daily or dalteparin 2500 IU once daily).
 
‘Importantly for GPs, we deliberately frame it as patients with “moderate disease” regardless of whether they’re in hospital or not, because we very much have the feeling that the decision to hospitalise may vary across institution or across time,’ Associate Professor Elliott said.
 
‘So you can imagine scenarios where people with mild disease might be hospitalised or, conversely, if we started to see very high numbers, patients with moderate disease may not be hospitalised. So because people with moderate disease are unwell even if they’re at home, the recommendation is that they receive VTE prophylaxis.’
 
Evidence on higher prophylactic doses versus standard in adults with severe or critical COVID-19 is currently under review.
 
Other evidence under review includes:

• concomitant use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers
• use of neuromuscular blocking agents
• use of nitric oxide
• use of corticosteroids
• timing of mechanical ventilation
• low versus high positive end-expiratory pressure (PEEP) thresholds.

Expert panels are also starting to look at developing guideline recommendations on issues regarding the retrieval of patients from rural and remote areas.


‘While we move quickly, we also have to make sure we’re following rigorous processes to make sure we’re not making mistakes or jumping too early,’ taskforce Chair Associate Professor Julian Elliott said.

The Australian living guidelines for the clinical care of people with COVID-19 will continue to be updated weekly.
 
First launched in April, the initiative was a response to the pressing need for a single source of trusted information, with healthcare professionals feeling overwhelmed amid the COVID-19 pandemic. With Australia now in a relatively strong position in terms of flattening the curve, following the success of stringent social distancing measures, Associate Professor Elliott says the sentiment has changed.
 
‘It’s not so much anxiety at the moment as a desire to be prepared – that’s very much the sense that we’re getting from clinicians through the submitted questions,’ he said.
 
‘There’s a lot of information coming out and it’s just, again, trying to create that solid, trustworthy source so that we all know what to do if cases do start to increase again.’
 
With close to 3000 new papers and articles published on COVID-19 in one week alone, it is clear that there is a strong desire to move rapidly in this space. While the taskforce acknowledges the urgent need for both progress and information, Associate Professor Elliott believes this highlights more than ever the importance of expert review panels during the pandemic.
 
‘At a time like this, it’s very easy to have confused messages because there’s a lot of hype,’ he said. ‘While we move quickly, we also have to make sure we’re following rigorous processes to make sure we’re not making mistakes or jumping too early,’ he said.
 
‘The last few weeks have shown how various treatments can get a lot of hype and traction and then even a few days later you get a little bit more information and it tends to temper that and that dies away, and then something else kind of grabs the attention.
 
‘So in the middle of that flurry of activity and attention we just need to make sure we’ve got processes that are very rigorous but also moving very quickly – quicker than we’ve ever done before.’
 
GPs are encouraged to submit their clinical questions and provide feedback on the taskforce website.
 
The RACGP has more information on coronavirus available on its website.
 
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clinical guidelines coronavirus COVID-19

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