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Communique

Communique # 39

25 February, 2021

WEEK IN REVIEW

UPDATES TO THE LIVING GUIDELINE

Tocilizumab upgraded to conditional recommendation
The Taskforce Disease Modifying Treatment and Chemoprophylaxis Panel and the Guidelines Leadership Group have incorporated the results of the tocilizumab arm of the RECOVERY Trial (released on February 11) into the body of evidence underpinning the Taskforce’s recommendation on the use of tocilizumab.

Evidence for this recommendation now comes from nine randomised trials that compare tocilizumab with standard care in 6390 adults hospitalised with COVID-19. The majority of data are from the RECOVERY trial, which included 4116 adults hospitalised with moderate to critical COVID-19. There was variability in disease severity among patients included in the trials.

As a result of this meta-analysis the Taskforce has determined that in patients hospitalised with COVID-19 who require supplemental oxygen, tocilizumab probably reduces the risk of death and therefore makes a conditional recommendation for tocilizumab use.

The upgraded recommendation is:

Consider using tocilizumab for the treatment of COVID-19 in adults who require supplemental oxygen, particularly where there is evidence of systemic inflammation.

In addition, the RECOVERY and REMAP-CAP (published as a pre-print on 7 January) trials have demonstrated a significant benefit of using corticosteroids in conjunction with tocilizumab. Use of combined tocilizumab and corticosteroids should be considered in patients hospitalised with COVID-19 who require oxygen, however the optimal sequencing of tocilizumab and corticosteroids is unclear.

As published on 29 January, and to investigate the contrasting mortality effect shown by the REMAP-CAP preliminary results (strong mortality benefit in patients with critical illness who were receiving organ support) with that of then existing Taskforce meta-analysis of five randomised trials (no mortality benefit observed), the Taskforce undertook an ICEMAN analysis to determine whether the apparent differences may be explained by differences in disease severity. Results from that analysis suggested it was inappropriate to analyse data in subgroups based on disease severity.

Following publication of the RECOVERY tocilizumab results, the Taskforce updated the ICEMAN analysis to determine whether the inclusion of the RECOVERY data affected the appropriateness of the subgroup analyses. Results from the updated analysis suggest that it is still likely to be inappropriate to analyse data in subgroups based on disease severity. The full ICEMAN analysis can be found here.

New recommendations

  • Sulodexide
  • Tocilizumab

Updated recommendations

  • Sofosbuvir-daclatasvir

Further details about these recommendations are below.

IPC Panel Update

The Taskforce IPC Panel is currently reviewing evidence to evaluate the effectiveness of:

  •  Face masks
  •  Eye protection
  •  Levels of ventilation
  •  Portable air cleaning devices
  •  Reduction in patient occupancy

Our 17-member panel draws on some of Australia’s foremost experts in evidence-based clinical practice, infection prevention and control, occupation and environmental health, occupational hygiene and clinical engineering.

The Taskforce is currently recruiting frontline healthcare workers to participate in a series of consultations to provide feedback on the implementability of draft IPC recommendations.

Consultation participants will be:

  • Frontline healthcare workers who are at risk of coming into contact with people diagnosed with, or suspected of, COVID-19.
  • People with frontline clinical experience caring for and managing patients diagnosed with, or suspected of, COVID-19.

For further information or to apply, please contact Taskforce secretariat Samantha Timms before Monday March 1.

Seeking consumers and carers with lived experience of COVID-19 for Consumer Panel

The Taskforce is looking for a diverse range of people with lived experience of COVID-19 to join the Consumer Panel. If you have experienced COVID-19, or have been a carer of someone with COVID-19, and would like to contribute to the national guidelines for the clinical care of people with COVID-19 please apply here by 5pm, Monday March 8.

The Consumer Panel is a collaboration between the Taskforce and the Consumers Health Forum of Australia (CHF).

 

QUICK STATISTICS

COVID-19 research pipeline

  • 45,941 studies published or registered in Cochrane COVID-19 Study Register, 1,810 added this fortnight
  • 2,590 randomised controlled trials registered (data from Covid-nma site), 64 added this fortnight
  • 3,330 systematic reviews registered in PROSPERO, 122 added this fortnight
  • 206 randomised controlled trials published (data from Covid-nma site), 26 added this fortnight

 

LIVING GUIDELINES

Australian guidelines for the clinical care of people with COVID-19: Version 35.0

NEW RECOMMENDATIONS

  • Sulodexide

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

  • Tocilizumab

Consider using tocilizumab for the treatment of COVID-19 in adults who require supplemental oxygen, particularly where there is evidence of systemic inflammation.

In patients hospitalised with COVID-19 who require supplemental oxygen, tocilizumab probably reduces the risk of death. Because of this, the Taskforce makes a conditional recommendation for tocilizumab both within and outside the context of a randomised trial unless contraindicated (e.g. patients with other active, severe infections).

In accordance with the RECOVERY trial, tocilizumab should be administered as a single intravenous infusion over 60 minutes, with the potential for a second dose to be administered either 12 or 24 hours later if the patient’s condition has not improved. The suggested dose is dependent on body weight:
Patients > 90 kg: 800 mg tocilizumab
Patients > 65 and ≤ 90 kg: 600 mg tocilizumab
Patients > 40 and ≤ 65 kg: 400 mg tocilizumab
Patients ≤ 40 kg: 8 mg/kg tocilizumab

In addition, the RECOVERY and REMAP-CAP trials have demonstrated a significant benefit when using corticosteroids in conjunction with tocilizumab. Use of combined tocilizumab and corticosteroids should be considered in patients hospitalised with COVID-19 who require oxygen, however the optimal sequencing of tocilizumab and corticosteroids use is unclear.

As tocilizumab inhibits the production of C-reactive protein (CRP), a reduction in CRP after administration of tocilizumab should not be used as a marker of clinical improvement.

UPDATED RECOMMENDATIONS

  • Sofosbuvir-daclatasvir

Updated evidence base with no change to the strength or direction of the recommendation

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

 

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 UPDATED
  • Preparedness for CPR during the COVID-19 pandemic
  • CPR for adults with COVID-19 in healthcare settings UPDATED
  • Basic life support for adults in the community during the pandemic

Changes to flowcharts this week include:

  • Addition of tocilizumab to disease modifying treatments
  • Addition of sulodexide to ‘only in clinical trials’
  • Text updated for clarity in goals of care in post COVID chart
  • Updated wording for Post Intensive Care Syndrome in post COVID chart
  • Updated reference versions for CPR in healthcare settings chart

 

EVIDENCE UNDER REVIEW

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

  • Anakinra NEW
  • Nitazoxanide NEW
  • Levels of ventilation
  • Portable air cleaning devices
  • Reduction in patient occupancy
  • Face masks
  • Eye protection
  • Ivermectin
  • Ivermectin plus doxycycline
  • Sarilumab
  • Convalescent plasma
  • Favipiravir
  • Post-exposure hydroxychloroquine prophylaxis
  • Immunoglobulin plus methylprednisolone
  • Zinc
  • Care of people with post acute COVID-19

 

NEW & EVENTS

Cochrane

Cochrane recently published a systematic review on Chloroquine or hydroxychloroquine for prevention and treatment of COVID‐19, with findings in line with the Taskforce HCQ/CQ recommendations:

  • Hydroxychloroquine does not reduce deaths from COVID-19, and probably does not reduce the number of people needing mechanical ventilation.
  • Hydroxychloroquine caused more unwanted effects than a placebo treatment, though it did not appear to increase the number of serious unwanted effects.
  • The authors do not think new studies of hydroxychloroquine should be started for treatment of COVID-19.

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