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Communique

Communique # 37

29 January, 2021

Following a well-earned break, the Taskforce team has now returned to full capacity. Global evidence surveillance continued throughout January, with six clinical panel meetings held since January 11. We look forward to continuing to keep Australian clinicians armed with the latest evidence-based guidance for the treatment of people with COVID-19. 

 

WEEK IN REVIEW

UPDATES TO THE LIVING GUIDELINE

Taskforce recommendation for tocilizumab unchanged
The Taskforce Disease Modifying Treatments and Chemoprophylaxis Panel and the Guidelines Leadership Group have incorporated the results of the tocilizumab arm of the REMAP-CAP trial (published as a pre-print on January 7, 2021) into the body of evidence underpinning the Taskforce’s recommendation on the use of tocilizumab. There remains uncertainty whether tocilizumab is more effective and safer than standard care in treating patients with COVID-19. As a result, the guidance remains unchanged and the Taskforce recommends that tocilizumab is only used in the treatment of COVID-19 in the context of randomised trials.

The REMAP-CAP preliminary results (yet to be peer reviewed) suggest a mortality benefit in patients with critical illness who were receiving respiratory or cardiovascular organ support. These data contrast with the pre-existing meta-analysis of five randomised trials conducted by the Taskforce, in which a mortality benefit was not observed in patients using tocilizumab. Importantly, the vast majority of relevant data published before REMAP-CAP focused on patients with moderate to severe illness, with the exception of the COVACTA trial which included 108 patients with critical illness.

To determine whether the apparent differences in effect on mortality might be explained by differences in disease severity, the Taskforce assessed the credibility of these subgroups using the Instrument to assess the Credibility of Effect Modification Analyses (ICEMAN).

This analysis indicates that it is likely to be inappropriate to analyse data in subgroups based on disease severity. The full ICEMAN analysis can be found here.

With the incorporation of data from the REMAP-CAP trial into the tocilizumab meta-analysis, the Taskforce identified a trend towards benefit, but uncertainty remains.

The Taskforce is awaiting the expected peer-reviewed publication of these data, the publication of the tocilizumab arm of the RECOVERY trial, and is currently reviewing another study comparing tocilizumab with standard care in adults receiving supplemental oxygen or mechanical ventilation (Veiga et al. BMJ doi: 10.1136/bmj.n84).

Recommendations regarding the use of tocilizumab will be updated as appropriate in future versions of the guidelines.

Azithromycin recommendation updated to Do Not Use
The Taskforce has updated the azithromycin recommendation to include recently published data from the RECOVERY trial, which included over 7,700 patients with mild to critical COVID-19 illness. Results demonstrated no difference in mortality or requirement of mechanical ventilation/ECMO in patients treated with azithromycin compared to those receiving standard care. The Taskforce has revised the previous guidance advising that azithromycin should only be used to treat COVID-19 in the context of randomised trials, to recommending that azithromycin is not used to treat COVID-19.

New recommendations

  • Baricitinib
  • REGN-COV2
  • Sarilumab

Updated recommendations

  • Azithromycin
  • Tociluzimab
  • Convalescent plasma (new remark)

Further details about these recommendations are below.

 

QUICK STATISTICS

COVID-19 research pipeline

  • 41,620 studies published or registered in Cochrane COVID-19 Study Register, 6,791 since 17/12/20
  • 2,454 randomised controlled trials registered (data from Covid-nma site), 192  since 17/12/20
  • 3,062 systematic reviews registered in PROSPERO, 275 since 17/12/20
  • 174 randomised controlled trials published (data from Covid-nma site), 27 since 17/12/20

 

LIVING GUIDELINES

Australian guidelines for the clinical care of people with COVID-19: Version 33.0

NEW RECOMMENDATIONS

  • Baricitinib

Do not use baricitinib for the treatment of COVID-19 outside of randomised trials with appropriate ethical approval.

  • REGN-COV2

Do not use REGN-COV2 for the treatment of COVID-19 outside of randomised trials with appropriate ethical approval.

  • Sarilumab

Do not use sarilumab for the treatment of COVID-19 outside of randomised trials with appropriate ethical approval.

UPDATED RECOMMENDATIONS

  • Azithromycin

The evidence base has been updated and the recommendation has been changed from ‘do not use outside of randomised trials’ to ‘do not use’.

  • Tocilizumab

The evidence base has been updated with no change to the strength or direction of the recommendation.

  • Convalescent Plasma

Text has been added to the ‘Remark’ section of the recommendation regarding the recent statement from chief investigators of the RECOVERY trial.

The Taskforce is continually monitoring research to update recommendations as new evidence accumulates.

 

CLINICAL FLOWCHARTS

11 clinical flowcharts have been developed by the Taskforce to cover:

  • Assessment for suspected COVID-19
  • Management of adults with mild COVID-19 UPDATED
  • Management of adults with moderate to severe COVID-19 UPDATED
  • Management of adults with severe to critical COVID-19 UPDATED
  • Respiratory support for adults with severe to critical COVID-19
  • Management of people with COVID-19 who are older and living with frailty and/or cognitive impairment
  • Management of people with COVID-19 who are receiving palliative care
  • Care of people who experience symptoms post acute COVID-19
  • Preparedness for CPR during the COVID-19 pandemic
  • CPR for adults with COVID-19 in healthcare settings
  • Basic life support for adults in the community during the pandemic

Changes to flowcharts this week include:<

  • Azithromycin added to ‘Do not use’ medications
  • ‘Only in research’ medications updated to include baricitinib, REGN-COV2, sarilumab

 

EVIDENCE UNDER REVIEW

We are currently reviewing evidence to develop recommendations and flowcharts to guide practice in areas including:

  • Sulodexide NEW
  • Bamlanivimab
  • Colchicine
  • Convalescent plasma
  • Favipiravir
  • Post-exposure hydroxychloroquine prophylaxis
  • Immunoglobulin plus methylprednisolone
  • Ivermectin
  • Sofosbuvir-daclatasvir
  • Zinc
  • Care of people with post acute COVID-19

 

NEWS & EVENTS

Cochrane
Since late December Cochrane has published:

The full list of Cochrane Reviews and related content from the Cochrane Library relating to the COVID-19 pandemic can be found here.

NEW TOPICS AND QUESTIONS

It is a core mission of the Taskforce to engage with frontline clinicians to rapidly identify and address priority clinical questions.

Each week we collect suggestions for new clinical questions or topics for consideration by the Taskforce. A document that lists all of the suggested questions, topics and new patient groups that we have received to date is available here.

Please encourage your clinical colleagues to provide their insights via the website.

Topics