REMAP-CAP
New REMAP-CAP trial results
New results from the REMAP-CAP trial have found that oseltamivir – long considered a standard treatment for influenza (flu) – appears to increase the risk of death in patients who are critically ill in an intensive care unit (ICU).
Australian ICUs have been asked to pause its use in critically ill patients while these initial results are reviewed.
Study Aims:
The primary objective of this adaptive platform trial is, for patients hospitalised with a respiratory tract infection, to evaluate the effect of a range of interventions to improve patient outcomes. A secondary objective is to provide a research platform that is able to respond in the event of a pandemic to rapidly and efficiently generate high-quality evidence to guide patient care.
Background and Rationale:
Respiratory tract infections that are of sufficient severity to require admission to hospital are associated with substantial mortality. All hospitalised patients with respiratory tract infections will receive therapy that consists of a combination of multiple different treatments. Of all the treatments that clinicians use for patients with respiratory tract infections, only a small minority have been tested in randomised controlled trials to determine their comparative effectiveness.
REMAP-CAP enrols hospitalised patients with respiratory tract infections using a trial design known as a REMAP, which is a type of platform trial. Within this platform trial, eligible participants may be randomised to receive one intervention in each of one or more domains.
In a conventional trial enrolment continues until a pre-specified sample size is obtained, at which time enrolment ceases and the trial data are analysed to obtain a result. The possible results are that a difference is detected, or no that no difference is detected. However, when the conclusion of the statistical test is “no difference”, this could reflect that there truly is no meaningful difference or that the result is indeterminate (i.e., it is possible that if more patients had been enrolled a clinically relevant difference may have been detected). In comparison to a conventional trial this Platform uses an adaptive design that:
- avoids indeterminate results by concluding an answer to a question when sufficient data have accrued (not when a pre-specified sample is reached);
- utilises already accrued data to increase the likelihood that patients within the trial are more likely to be randomised to treatments that are more likely to be beneficial;
- is intended to be perpetual (or at least open-ended), substituting new questions in series as initial questions are answered; and
- can evaluate the interaction between interventions in different domains, added at different timepoints into the Platform.
Study progress:
REMAP-CAP commenced recruitment in 2016. At the outbreak of the COVID-19 pandemic, REMAP-CAP rapidly expanded to involve more than 360 participating sites in 30 countries. To date, more than 50 different interventions across more than 20 domains of therapy have been evaluated in REMAP-CAP. The results generated from this trial have been published in leading medical journals, incorporated into treatment guidelines, and have influenced the care of millions of patients globally.
Partners:
The ANZIC-RC collaborates with a number of partners on REMAP-CAP. This trial is sponsored in New Zealand by MRINZ; in Europe by UMC Utrecht and ECRAID, in Canada by Unity Health, Toronto; in Japan by St Marianna University; and in Singapore by National University Hospital.
Statistical support is provided by Berry Consultants, and data management is provided by ICNARC.
In Australia, REMAP-CAP is federated with the ASCOT trial, sponsored and coordinated by the University of Melbourne.
Funding:
REMAP-CAP has received funding from the NHMRC, MRFF and Minderoo Foundation in Australia. Globally, it has been supported by the Health Research Council of New Zealand; The Canadian Institute of Health Research; the Japanese Agency for Medical Research and Development; the National Institute of Health Research (NIHR) of the United Kingdom; the European Union; The French Ministry of Health; and the Health Research Board of Ireland.
In addition, REMAP-CAP has been supported by infrastructure provided by the NIHR in the UK, the New South Wales Adaptive Platform Trial Operating Plan in Australia, and Wellcome-Oxford Innovations Flagship – Collaboration for Research Implementation and Training in Asia.
Public website:
Trial registration:
https://clinicaltrials.gov/study/NCT02735707