Story for NHMRC, published in 2020
A clinical trial made for a pandemic is racing for answers
Over 180 intensive care units in 14 countries are trialling more than 20 pneumonia treatments to save the lives of critically ill COVID-19 patients. The trial, REMAP-CAP, is an adaptive clinical trial built to deliver fast results in a pandemic and is now one of three key national trials identified by the UK government.
NHMRC supported the development of REMAP-CAP with initial funding of $4.4 million in 2015 (as OPTIMISE-CAP) and has provided additional COVID-19 related support of $25,000 via the Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE).
Around the world, ICUs are being overwhelmed by critically ill patients with life-threatening pneumonia. “We need to identify interventions that can reduce mortality and reduce ICU length of stay,” says Professor Steve Webb, Chair of the International Trial Steering Committee and Chief Investigator in Australia of REMAP-CAP. “We are currently simultaneously testing seven areas of treatment (domains) for COVID-19 including antivirals, immune modulation, antibodies, anticoagulants, macrolides, corticosteroids and vitamin C.”
REMAP-CAP has been years in development, but it’s been expanded at breakneck speed in response to COVID-19. Recruitment of COVID-19 patients reached 471 in mid-May. The team anticipate reaching 1000 over the coming months.
“In the ICU a clinician can enrol a patient in less than five minutes, and they can choose from a smorgasbord of treatment options customised for their intensive care unit,” says Webb. “The complexity is hidden ‘under the bonnet’, with Bayesian statistics driving the simultaneous trial of multiple interventions,” says Webb, who is both an ICU clinician at the Royal Perth Hospital and a Monash University researcher.
The Chief Medical Officers of the United Kingdom have identified REMAP-CAP as one of three key national trials for COVID-19. In a public statement calling for enrolments they say, “As yet, there are no proven treatments for COVID-19. We need to gather reliable evidence through clinical trials … These trials are being run as simply as they can to reduce the burden on the NHS, with adaptive designs so further treatments can be added if new promising candidates are identified.” Their full statement is at https://bit.ly/3bvxOOo.
“The rapid rollout has only been possible because of years of pre-pandemic preparation by the research team, backed by the European Union, and the Australian, New Zealand, and Canadian governments,” says Professor Allen Cheng, a member of the International Trial Steering Committee and an investigator on the Australian arm of the study.
It all started with a group of ICU clinician researchers who were trying to save lives during the swine flu pandemic. In 2009, Webb was working in an ICU with every ventilator in use. Then a seriously ill ‘flu patient was admitted to emergency.
Two major lessons came out of the ‘flu pandemic for Webb and his colleagues:
- That lives could be saved in ICU if we had a better understanding of community acquired pneumonia and improved options for treating it;
- That a new approach was needed to rapidly trial treatment options and improve patient outcomes during a pandemic.
- So, a small group started designing alternatives.
Today, REMAP-CAP’s Australian investigators comprise Steve Webb, Allen Cheng and Alistair Nichol, all from Monash; Ed Litton (UWA); Jeff Presneill (University of Melbourne); and Peter Kruger (University of Queensland). They are working with leading clinicians and researchers from Canada, the US, Saudi Arabia, Germany, the Netherlands, France, Ireland and the UK. The members of the international trial steering committee are listed at https://www.remapcap.org/remapcap-itsc.
The European Union was the first major supporter followed by Australia’s National Health and Medical Research Council, the Health Research Council of New Zealand, the Canadian Institutes of Health Research, the Irish Health Research Board, and the UK National Institute for Health Research. The global expansion of REMAP-CAP, as well as preparedness in Australia, has also been generously supported by the Minderoo Foundation.
Recruitment started in 2018, looking at three areas of intervention for pneumonia. Participants reached 340 by the end of 2019.
Then, COVID-19. “On 23 January we held our first meeting of collaborators, by middle of March we’d adapted the trial to include specific COVID-19 treatments, and our collaborators around the world started enrolling patients in the expanded study,” says Webb.
The seven domains of COVID-19 treatment being evaluated are:
• Antiviral therapies
• Immune Modulation therapy
• Antibody therapy with convalescent plasma
• Therapeutic anticoagulation, evaluating forms of heparin
• High dose vitamin C
And two of the trial’s original domains that are appropriate for COVID-19:
• Prolonged macrolide antibiotic therapy to modulate immune function
• Corticosteroid strategies.
For further information visit: https://www.remapcap.org/
For updates on the treatment domains visit https://www.remapcap.org/coronavirus