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Communique

Communique # 51

15 October, 2021

WEEK IN REVIEW


Updates to the Living Treatment Guidelines

New recommendations

New recommendation for Continuous positive airway pressure / High-flow nasal oxygen therapy
The Hospital and Acute Care Panel have incorporated the results of the recent RECOVERY-Respiratory Support trial (Perkins et al.) into the evidence base for respiratory support. The previous recommendation for High flow nasal oxygen therapy (HFNO) was based on indirect evidence but with the additional randomised trial data the Taskforce has revised the conditional recommendation to:

Consider using continuous positive airway pressure (CPAP) therapy for patients with persistent hypoxaemia (defined as requiring an FiO2 ≥ 0.4 to maintain SpO2 in their target range) associated with COVID-19. Adjust positive end-expiratory pressure as required, most patients require pressures of 10 to 12 cm. Excessive pressures may increase the risk of pneumothorax. Adjust oxygen to maintain SpO2 in the target range, FiO2 0.4 to 0.6.Patients requiring CPAP for COVID-19 pneumonia are at high risk of further deterioration, requiring intubation and mechanical ventilation. Liaise with ICU and monitor closely for deterioration.

If CPAP is not available or not tolerated, consider HFNO as an alternative using the same safety parameters as CPAP.

Six new treatment recommendations for children and adolescents
Sotrovimab for children and adolescents
Following recent recommendations on the use of sotrovimab in adults, the Taskforce has reviewed the evidence in the context of children and adolescents and developed two new recommendations:

  • Only in research recommendation’ for children or adolescents under 12 years of age and without high-risk factors for deterioration.
  • Consensus recommendation’ for sotrovimab to be considered in exceptional circumstances for children and adolescents aged 12 years and over and weighing at least 40 kg with mild COVID-19 and at high risk of deterioration.

The recommendations also include additional information in the remarks recognising that children were not included in the COMET-ICE Trial, however trials are underway in which children over 12 years of age are eligible for inclusion (OPTIMISE-C19NCT04913675).

Casirivimab plus imdevimab (Ronapreve/REGEN-COV) for children and adolescents
The Paediatric and Adolescent Care Panel has also reviewed the casirivimab plus imdevimab for adults recommendation and has developed three new recommendations for children and adolescents.

  • Consensus recommendation’ for casirivimab plus imdevimab to be considered in exceptional circumstances in seronegative children and adolescents aged 12 years and over and weighing at least 40 kg with moderate to critical COVID-19 who are at high risk of disease progression.
  • Do not use recommendation‘ for seropositive children or adolescents hospitalised with moderate to critical COVID-19
  • Only in research recommendation‘ for children under 12 years of age without risk factors for deterioration who have mild or asymptomatic COVID-19.

Casirivimab plus imdevimab is not currently available for use within Australia.

Budesonide for children and adolescents
The Taskforce has made a new conditional recommendation to consider using inhaled budesonide for the treatment of symptomatic COVID-19 in children and adolescents who do not require oxygen and who have one or more risk factors for disease progression.

In adult patients with confirmed COVID-19 who do not require oxygen but who are subsequently hospitalised due to disease progression, budesonide probably decreases the requirement of supplemental oxygen if taken within 14 days of onset of symptoms.

Results are primarily based on the PRINCIPLE trial, in which adults were treated with inhaled budesonide (by breath actuated inhaler) 800 µg twice daily for up to 14 days. No children or adolescents were included in the trial.

Doxycycline added to list of ‘only in research’ recommendations
The Taskforce has reviewed the evidence from the PRINCIPLE trial that compared doxycycline with standard care in 1792 adults with mild COVID-19.

It remains unclear whether doxycycline is more effective than standard care in treating patients with COVID-19 and as a result the Taskforce recommends that doxycycline should not be used for the treatment of COVID-19 outside randomised trials.

Updated recommendation for use of systemic corticosteroids in pregnant women
In response to feedback from clinicians, the Taskforce has updated the corticosteroids for pregnant or breastfeeding women recommendation to support the use of a slightly higher dose of dexamethasone if steroids are indicated for fetal lung maturity in women at risk of preterm birth.

  • Budesonide for adults – The remark and preferences and values have been updated to include information on safety of budesonide in pregnant and breastfeeding women.
  • Fluvoxamine – updated evidence, no change to stre
  • Corticosteroids for pregnant or breastfeeding women –  updated remark and rationale

Further details about these recommendations and additional updates are below.

Taskforce awaits further trial data on molnupiravir
The Taskforce notes the recent media release published by Merck/MSD and Ridgeback Biotherapeutics (1 October 2021) regarding the oral antiviral, molnupiravir and its use in adult patients with mild-to-moderate symptoms.

The makers announced that molnupiravir reduced the risk of hospitalisation or death from COVID-19 by 50 per cent at a planned interim analysis of the Phase 3 MOVe-OUT trial.

The Taskforce awaits further published trial data before it considers a recommendation.

Taskforce Executive Director passes the leadership baton
Founding Executive Director of the Taskforce, Professor Julian Elliott, this week stepped down as leader after 18 months at the helm.

Prof Julian ElliottJulian was instrumental in the establishment of the Taskforce in March 2020. With a vision to provide clear, unified and up-to-date evidence-based guidance for clinicians caring for people with COVID-19, he worked tirelessly with long-time collaborator Rhiannon Tate to bring together Australia’s leading peak health organisations and secure funding from government and philanthropy within the space of three weeks. A world leader in the development of living clinical guidelines, Julian is stepping back to focus on his role as Chair of the Australian Living Evidence Consortium (ALEC). The Taskforce pivoted out of ALEC at the start of the pandemic and will now formally join five other chronic disease areas to become a formal member of ALEC.

Julian is handing over leadership of the Taskforce to Associate Professor Steve McGloughlin, Director of The Alfred Intensive Care Unit and a founding panel member of the Taskforce.

Steve has already been an extraordinary and generous contributor to the Taskforce; co-chairing the Critical Care Panel, member of the Infection Prevention and Control Group and member of the Guidelines Leadership Group.

A/Prof Steve McGloughlinHe is dual trained in infectious diseases and intensive care and has had a truly national career working in most Australian states. He has also worked in Cairns, Darwin and remote Queensland with the Royal Flying Doctor Service, and has masters in both public health and health leadership.

As Head of ICU at The Alfred, Steve has cared for some of the nation’s sickest patients and is well-placed to understand the ongoing challenges faced by clinicians during the pandemic.

The Taskforce warmly welcomes Steve as Executive Director and looks forward to his leadership into the next phase.

 

QUICK STATISTICS

COVID-19 research pipeline

  • 90,466 studies published or registered in Cochrane COVID-19 Study Register, 1,912 added this week
  • 3,540 randomised controlled trials registered (data from Covid-nma site), 20 added this week
  • 5,414 systematic reviews registered in PROSPERO, 51 added this week
  • 464 randomised controlled trials published (data from Covid-nma site), 11 added this week

 

LIVING GUIDELINES

Australian guidelines for the clinical care of people with COVID-19: Version 44.0

NEW RECOMMENDATIONS

  • Budesonide for children and adolescents

Conditional recommendation
Consider using inhaled budesonide for the treatment of symptomatic COVID-19 in children and adolescents who do not require oxygen and who have one or more risk factors for disease progression.

  • Casirivimab plus imdevimab (Ronapreve/REGEN-COV) in children and adolescents

Consensus recommendation
Consider using, in exceptional circumstances, casirivimab plus imdevimab in seronegative children and adolescents aged 12 years and over and weighing at least 40 kg with moderate to critical COVID-19 who are at high risk of disease progression.

Not recommended
Do not use casirivimab plus imdevimab in seropositive children or adolescents hospitalised with moderate to critical COVID-19.

Only in research
Do not use casirivimab plus imdevimab in children under 12 years of age without risk factors for deterioration who have mild or asymptomatic COVID-19 outside of randomised trials with appropriate ethical approval.

  • Sotrovimab for children and adolescents

Only in research
Do not routinely use sotrovimab outside of randomised trials with appropriate ethical approval for the treatment of COVID-19 in children or adolescents under 12 years of age and without high-risk factors for deterioration.

Consensus recommendation
Sotrovimab should be considered in exceptional circumstances for children and adolescents aged 12 years and over and weighing at least 40 kg with mild COVID-19 and at high risk of deterioration.

Consider using sotrovimab only in unvaccinated or partially vaccinated children and adolescents or those who are immunosuppressed regardless of vaccination status. Do not routinely use sotrovimab in fully vaccinated patients unless immunosuppressed.

Decisions about the appropriateness of treatment with sotrovimab should be based on the patient’s individual risk of severe disease, on the basis of age or multiple risk factors, and COVID-19 vaccination status.

  • Doxycycline

Only in research
Do not use doxycycline for the treatment of COVID-19 outside of randomised trials with appropriate ethical approval.

  • Continuous positive airway pressure  / High-flow nasal oxygen therapy

Conditional recommendation
Consider using continuous positive airway pressure (CPAP) therapy for patients with persistent hypoxaemia (defined as requiring an FiO2 ≥ 0.4 to maintain SpO2 in their target range) associated with COVID-19. Adjust positive end-expiratory pressure as required, most patients require pressures of 10 to 12 cm. Excessive pressures may increase the risk of pneumothorax. Adjust oxygen to maintain SpO2 in the target range, FiO2 0.4 to 0.6.

Patients requiring CPAP for COVID-19 pneumonia are at high risk of further deterioration, requiring intubation and mechanical ventilation. Liaise with ICU and monitor closely for deterioration.

If CPAP is not available or not tolerated, consider HFNO as an alternative using the same safety parameters as CPAP.

UPDATED RECOMMENDATIONS

  • Budesonide for adults

The remark and preferences and values sections of the budesonide recommendation have been updated to include information regarding safety of budesonide in pregnant or breastfeeding patients.

  • Corticosteroids for pregnant and breastfeeding patients

The remark and rationale sections of the corticosteroids for pregnant or breastfeeding patients recommendation have been updated to include information regarding the use of dexamethasone for fetal lung maturity.

  • Fluvoxamine

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 UPDATED
  • Management of adults with mild COVID-19 UPDATED
  • Management of adults with moderate to severe COVID-19
  • Management of adults with severe to critical COVID-19
  • Respiratory support for adults with severe to critical COVID-19 UPDATED
  • 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 with 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 the flowcharts this week reflect:

  • Minor alterations to the Assessment chart
  • Mild chart updated to reflect budesonide recommendation in adults
  • Updated guidance on CPAP/HFNO in respiratory support chart

 

EVIDENCE UNDER REVIEW

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

  • Casirivimab plus imdevimab
  • Corticosteroids
  • Hydroxychloroquine plus azithromycin
  • Immunoglobulin plus methylprednisolone
  • Tocilizumab
  • VTE prophylaxis
  • Care of people with Post-acute COVID-19

NEWS & EVENTS

Cochrane

  • Engaging Evidence 2021— Registrations will soon be open for Engaging Evidence 2021 (EE21). EE21 brings together researchers and practitioners from the worlds of evidence synthesis and evidence implementation. The themes of EE21 encompass the broad scope of evidence production, synthesis, dissemination and implementation. Subscribe for updates.

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

World Evidence-Based Healthcare Day Events

  • COVID19 and misinformation: Working collaboratively to bring science to practice—As part of World Evidence-Based Healthcare (EBHC) Day 2021, the Guidelines International Network (GIN) together with the National Institute for Health and Care Excellence (NICE) will be hosting a free 90-minute interactive event to give an insight on how global health care agencies have come together in response to the pandemic. The event will commence with a presentation discussing the collaboration work between NICE (UK) and Monash University (Australia) in producing rapid COVID-19 guidelines during the pandemic.

Date: October 20, 2021
Time: 11am London
Presenters: Dr Fiona Glen, Dr Justine Karpusheff (NICE), A/Prof Tari Turner and Prof Julian Elliott (Monash).
Register here

  • Role of Evidence in an Infodemic—Individuals and organisations will be holding workshops, seminars, and masterclasses from 18–24 October 2021 about the need for better evidence to inform health policy and practice and encourage debate and discussion amongst the global evidence community. See full events list here.

 

NEW TOPICS & 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