Sepsis Immunomics
Research type
Research Study
Full title
The GAinS investigators: application of an integrated immune -omic approach in sepsis
IRAS ID
260007
Contact name
Julian C Knight
Contact email
Sponsor organisation
University of Oxford / Clinical Trials and Research Governance
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
This study aims to understand the molecular pathophysiology of sepsis in order to improve patient care. Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Currently we do not understand why only a minority of patients develop this extreme response to infection, why there is variability in the sepsis response and how best to identify specific sepsis patients who will benefit from particular treatments. This is important as in the UK, sepsis is a major public health burden, responsible for 1 in 20 deaths in England with few effective treatments. Mortality remains higher than 25-30% and up to 40-50% in severe cases. Nearly a third of UK ICU admissions are for patients with sepsis, where it is the most common cause of death. \n\nTo better understand sepsis biology and the individual sepsis response, we propose to recruit up to 1100 adult patients admitted to UK hospitals (including 300 control patients), especially intensive care units, for a prospective non-interventional observational study. Samples will include blood, urine, faeces, respiratory specimens. We will apply the most current immunological and functional genomic technologies to understand the nature of the sepsis response and its variability.\n\nThe study will initially be run at the John Radcliffe Hospital in Oxford, but other centres will then be included to increase patient recruitment with the study to run over 5 years. Processing of biological material will primarily be done at the Wellcome Centre for Human Genetics and Weatherall Institute of Molecular Medicine in Oxford.COVID-19 amendment – 06/03/2020. This amendment is being made after initial recruitment into the study has proceeded well. The proposal is based on 1) an area which can be improved for follow up sampling and 2) the current global outbreak of SARS-CoV-2 which causes the deadly disease Covid-19. For the first issue, the study design consists of a 3-6 month follow up sample from patients who have recovered from sepsis to examine the long term effects of the illness. The current sampling protocol allows for sampling either at a specific research site or at the hospital - however, partnering clinicians and research nurses have reported that patients who have suffered severe illnesses would much prefer not having to go back to the hospital and would prefer having follow up samples performed via home visits. We propose to amend the protocol in this 3-6 month follow up sample to allow for home visits to increase our rate of follow up sampling and allow the original objectives of the study to be achieved. For the second issue regarding SARS-CoV-2, it is clear from epidemiological studies that a significant proportion of patients infected with the novel coronavirus go on to develop severe disease, organ failure and sepsis. Understanding whom amongst those infected go on to develop sepsis will be of paramount importance in developing treatments and novel preventative strategies and medications for this deadly disease. However, it is noted that the duration before patients infected with the virus develop sepsis can vary and in a substantial proportion of cases, take days. Currently, the protocol does not allow recruitment of patients before they become fully septic and as such we would fail to recruit coronavirus patients early on enough in their disease course.To overcome this problem, we propose to extend the inclusion criteria of the study to those with a confirmed infection of SARS-CoV-2 who may not have fully developed sepsis yet. Sampling for these patients will then be performed in the same way as for current Sepsis Immunomics patients i.e. blood sampling at days 1, 3 and 5 of hospital admission. In addition, there is an urgent need to understand how the body produces antibodies to the coronavirus to enable vaccine development. This is best investigated by examining convalescent samples 4-6 weeks after recovery. We therefore propose that for this arm of the study that the follow up samples after hospital discharge are taken at 4-6 weeks rather than 3-6 months as in the other sepsis patients. The original protocol stipulates that samples will be processed and stored within secure alarmed facilities in the Wellcome Centre for Human Genetics. However, as we are envisaging this to eventually be a multi-centre study, we would like to amend this to any local Sepsis Immunomics laboratory. Moreover, with the additional Covid-19 arm to the study, locally at the University of Oxford, we would need to allow for sample processing and storage at theUniversity of Oxford’s Centre for Clinical Vaccinology and Tropical Medicine (CCVTM) to comply with UK legislation regarding schedule 5 pathogens. Finally, regarding data and sample sharing, patients have all along been explicitly consented for whether they agree for their de-identified samples and data to be used in other studies. The wording in the protocol under ethical considerations - consent and confidentiality has been updated to reflect this more clearly than in previous versions.
REC name
South Central - Oxford C Research Ethics Committee
REC reference
19/SC/0296
Date of REC Opinion
12 Jul 2019
REC opinion
Favourable Opinion