Background

• Community-acquired pneumonia (CAP), that is of sufficient severity to require admission to an Intensive Care Unit (ICU), is associated with substantial mortality.

• In Australia, CAP is responsible for more than 7000 ICU admissions and 1400 deaths each year. The annual direct cost of ICU care of these patients is in the order of $200 million.

• All patients with severe pneumonia who are treated in an ICU will receive therapy that consists of a combination of multiple different treatments.

• The existing evidence-base, for treatment of patients with Severe CAP is limited, reflected in variation in Australian and international guidelines as well as variation in practices including choice of antibiotic, choice of ventilator strategy, and use of immune modulating agents.

Trial Design

• The study will enrol adult patients with severe CAP who are admitted to ICUs using a design known as a REMAP, which is a type of platform trial.

• Eligible participants will be randomised to receive one intervention in each of one or more domains.

• This REMAP uses an adaptive design, relying on pre-specified criteria for adaptation, that:

  • Avoids indeterminate results

  • Concludes an answer to a question when sufficient data have accrued (not when a pre-specific sample is reached)

  • Evaluates the effect of treatment options in pre-defined subgroups of patients (termed strata)

  • Utilizes already accrued data to increase the likelihood that patients within the trial are randomized to treatments that are more likely to be beneficial

  • Is multifactorial, evaluating multiple questions simultaneously

  • Is intended to be perpetual (or at least open-ended), substituting new questions in series as initial questions are answered

  • Can evaluate the interaction between interventions in different domains.

• Bayesian statistical methods will be used to establish the superiority, inferiority, or equivalence of interventions within a domain. Interventions determined to be superior will be incorporated into standard care within the ongoing REMAP. Interventions determined to be inferior will be discontinued.

COVID-19 Update

REMAP-CAP was designed with a pandemic component targeting an expected influenza pandemic. Early in 2020 this was activated and adapted for COVID-19 research.

Primary Outcomes

Day 90 mortality for pneumonia patients.

Day 21 ventilator free days for Covid-19 patients.

Supporters

• National Health and Medical Research Council, (NHMRC) Australia

• The Health Research Council (HRC) of New Zealand

• European funding through the PREPARE consortium

• The Australia and New Zealand Intensive Care Research Centre

• The Medical Research Institute of New Zealand

• University Medical Center Utrecht

Contacts

• Cameron Green, Project Manager, The ANZIC Research Centre, Monash University.

• Professor Steve Webb, ANZ Executive Director, Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine, Monash University. steven.webb@monash.edu

• Jess Wren, EDC Platform Manager at Spiral