The Intensive Care Society’s research division has been working tirelessly on a variety of studies both before and after the outbreak of COVID-19. The Society has five Directors and Deputy Directors of research who have focused all their energy on COVID-19 studies.
The ISARIC 4C
The ISARIC 4C group is a leading consortium of professionals focused on the improving our understanding of COVID-19. Below is an insight into the studies our Directors and Deputy directors of research are involved with.
SARIC 4C (Coronavirus Clinical Characterisation Consortium)
- How long are people infectious, and what body fluids are infectious?
- What puts people at higher risk of severe illness?
- What is the best way to diagnose the disease?
- Who should we treat early with drugs, and which drugs cause harm?
- Does the immune system in some patients do more harm than good?
- What other infections (such as pneumonia or flu) happen at the same time?
The UK needs a coordinated response to answer these questions as quickly as possible. Over the last 8 years we have been preparing for such a major outbreak worldwide International Severe Acute Respiratory Infection Consortium Clinical Characterisation Protocol; our team deployed immediately and has been collecting data and samples since the first cases were reported in the UK.
ISARIC 4C is funded by a grant from UKRI (MRC) with a total value of £5.9 million to JK Baillie (PI), University of Edinburgh; MG Semple, University of Liverpool; and P Openshaw, Imperial College London (co-leads).
Research for Patients in Critical Care:
Dr Kenneth Baillie - ICS Deputy Director of Research
Professor Danny MacAuley - ICS Director of Research
Genetic study, consent needed
are (MRC/DHSC/FEAT/ICS/Wellcome-funded). UK-wide ICU study to identify variants underlying genetic susceptibility to critical illness with coronavirus, which may help identify new targets for treatment and mechanisms of disease. This study was funded in 2014 and was recruiting across the UK before the pandemic hit.
GenOMICC is now an NIHR urgent public health study and all COVID-19 patients are eligible to participate. So far there are 115 critical care units already signed up and we would encourage those who are yet to do so participate in this trial as soon as possible - https://genomicc.org/
Professor Danny MacAuley - ICS Director of Research
Randomised Evaluation of COVID-19 Therapy (MRC/DHSC-funded). Trial of widely available, high-priority interventions, among confirmed COVID-19 cases requiring hospital admission, to determine effect on death or requirement for invasive ventilation. Interventions will be added and removed over time as needed. Given the unprecedented impact COVID-19 will have on the health of the population, even small clinical benefits may be of significant benefit. Designed to give individual patients the best chance of getting an effective therapy. To do this we need GCP-trained research nurses to support front-line clinical staff recruiting patients.
RECOVERY-RS is a multi-centre, pragmatic clinical trial evaluating the use of CPAP and / or high flow nasal oxygenation to prevent intubation and reduce mortality. Uncertainty about the effectiveness of CPAP / HFNO in COVID-19 have led to conflicting guidance on the use of these interventions.
Since the trial was commissioned by the CMO’s office and is supported by the Intensive Care Society it has been made an urgent Public Health research priority (issued on 13 April, 2020).
The trial is seeking to recruit 4000 patients with acute respiratory impairment (FiO2 >0.4 and SpO2 < 94%). Sites may choose to enrol in one or both arms of the trial (CPAP versus standard care, HFNO versus standard care or CPAP versus HFNO versus standard care).
For more information and to sign up to participate in this trial please click the link: http://www.isrctn.com/ISRCTN16912075
REMAP-CAP: a platform trial for severely ill patients with COVID-19
Professor Anthony Gordon - ICS Director of Research
REMAP-CAP ( www.remapcap.org ) is an international adaptive platform trial that was specifically designed to be employed in a pandemic to evaluate multiple interventions simultaneously in critically ill patients. In the UK the trial is being led by Tony Gordon (ICS DOR) in conjunction with ICNARC. It has received UHP badging by the CMOs office and is listed as one of the UK’s prioritised platform trials.
Designed to generate answers quickly.
The platform is multi-factorial: each patient can be randomised to multiple treatments.
It uses frequent interim analyses: a question is concluded as soon as there is sufficient information to support a conclusion. Analyses can occur every week.
It detects superiority, inferiority, or equivalence of interventions within the platform.
Additional interventions are added, as required, based on availability and external evidence.
By assigning patients to 'recipes' of treatments, only a few patients receive no active therapy.
REMAP-CAP can recruit easily. The bedside clinician can enrol patients in minutes. The trial is a Bayesian adaptive platform trial, generating answers to many questions rapidly.
REMAP-CAP will study, on an open-label basis:
Antiviral therapy (no antiviral, lopinavir/ritonavir (Kaletra), hydroxychloroquine and the combination of both).
Corticosteroid strategy (no steroid, fixed 7 days, only while in septic shock).
Immune modulation (no modulator, interferon-beta, anakinra, and interleukin 6 inhibitors are being added).
Convalescent plasma is being added (led by Manu Shankar-Hari & David Menon with NHSBT).
Other interventions are in development.
The platform can evaluate interactions, e.g. do steroids work only when an active antiviral is administered?
Designed to improve outcome for participants
The platform uses response adaptive randomisation. After each interim analysis, the weighting of randomisation is modified so that patients are more likely to receive those interventions that are performing best.
The protocol design has now been published: https://www.atsjournals.org/doi/abs/10.1513/AnnalsATS.202003-192SD
If your ICU would like to sign up please contact: email@example.com.
The Society has been a long-term supporter of many of these studies which are now at the forefront of UK research against COVID-19 and is incredibly proud of both the pro-active and reactive research being undertaken by its Directors and Deputy Directors of research.
Please assist where you can with this vital research and sign up to participate in any study possible to ensure this research continues.