Functional Genomic Influences on Disease Progression and Outcome in Sepsis
- Conditions
- PeritonitisPneumonia
- Registration Number
- NCT00131196
- Lead Sponsor
- University of Oxford
- Brief Summary
The proposal is aimed at identifying genetic factors that determine the incidence and severity of, and the outcome from life-threatening infections (severe sepsis/septic shock) in patients admitted to High Dependency Units (HDUs) or Intensive Care Units (ICUs) with pneumonia which developed outside the hospital (community acquired pneumonia - CAP) or contamination of the abdominal cavity with faeces due to a leak in the bowel (faecal peritonitis). This will require the acquisition of a large, high quality resource of genetic material (DNA), plasma, urine, white blood cells and clinical information from well characterized groups of similar patients with, or at risk for, severe sepsis/septic shock. The principal objective is to perform studies which are sufficiently large to establish beyond doubt the influence of a series of selected "candidate" genes on the development, progress and outcome of sepsis.
- Detailed Description
The investigators plan to recruit 2,000 cases of community acquired pneumonia (CAP) and 2,000 cases of faecal peritonitis (FP) from 30 UK ICUs and HDUs (members of the UK Critical Care Genomics group - UKCCG). The large number of patients is required to satisfy the power calculations based upon the predicted allele frequencies of candidate genes and the level of functional expression of the gene polymorphisms.
If a patient is eligible, written, informed consent will be obtained either from the patient or, if the patient is incompetent via the patient's legal representative. Patients will be characterized clinically in terms of admission diagnosis, severity of illness (APACHE II), organ failures (SOFA) and final outcome (ICU and hospital mortality, death or survival 6 months following ICU admission. Date of death will be recorded when appropriate). Clinical status will be assessed daily for days 1, 2, 3, 5 and 7 of ICU admission using the Sepsis criteria, SOFA score, microbiological culture results and antibiotic therapy.
Selected ICUs will, following consent, also undertake blood and urine sampling on days 1, 3 and 5 for genomic, proteomic and metabolomic studies. Information will be recorded on a bar-coded paper clinical report form (CRF) at the bedside. The CRFs will be securely stored locally and copied to the research coordinator, where they will be archived. The data will be entered independently by the research coordinator and one of the investigators into a secure, central web-based electronic database for storage of clinical data and the calculation of derived values. The patient codes for genetic analysis will be derived directly from the clinical database. Those undertaking genotyping will be blinded to the clinical details and these two databases will be brought together at the time of analysis only under the direct supervision of one of the principal investigators.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 4000
- Patient, or legal representative, is able to give informed consent
- Male or female of 18 years or more
- Patient admitted to ICU/HDU with faecal peritonitis or community acquired pneumonia
- Patient or legal representative is unwilling to consent
- Patient is under the age of 18 years
- Patient is already enrolled in an interventional study
- Patient is immunocompromised
- Patient is pregnant
- There is an advance directive to withhold or withdraw life-sustaining treatment or patient is admitted for palliative care only.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method ICU and hospital Mortality ICU discharge, hospital discharge and 6 month. The date of death will be recorded, as appropriate, for each patient.
- Secondary Outcome Measures
Name Time Method Severity of illness, duration of organ support, shock reversal, duration of ICU and hospital stay From ICU admission to discharge
Trial Locations
- Locations (49)
Royal Blackburn Hospital
🇬🇧Blackburn, Lancashire, United Kingdom
Queen Elizabeth Hospital
🇬🇧Birmingham, West Midlands, United Kingdom
Royal Berkshire Hospital
🇬🇧Reading, Berkshire, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Royal Preston Hospital
🇬🇧Preston, Lancashire, United Kingdom
Antrim Hospital
🇬🇧Antrim, County Antrim, United Kingdom
Southend General Hospital
🇬🇧Southend, Essex, United Kingdom
Bristol Royal Infirmary
🇬🇧Bristol, Gloucestershire, United Kingdom
Withington Hospital
🇬🇧Manchester, Greater Manchester, United Kingdom
Hope Hospital
🇬🇧Manchester, Greater Manchester, United Kingdom
Frenchay Hospital
🇬🇧Bristol, South Gloucestershire, United Kingdom
Royal Sussex County Hospital
🇬🇧Brighton, Sussex, United Kingdom
Walsall Manor Hospital
🇬🇧Walsall, West Midlands, United Kingdom
UCLH Middlesex Hospital
🇬🇧London, United Kingdom
James Cook University Hospital
🇬🇧Middlesborough, Cleveland, United Kingdom
Colchester General Hospital
🇬🇧Colchester, Essex, United Kingdom
Cheltenham General Hospital
🇬🇧Cheltenham, Gloucestershire, United Kingdom
University Hospital Lewisham
🇬🇧Lewisham, London, United Kingdom
John Radcliffe Hospital
🇬🇧Oxford, Oxon, United Kingdom
University Hospital of Wales
🇬🇧Cardiff, South Glamorgan, United Kingdom
The Ipswich Hospital
🇬🇧Ipswich, Suffolk, United Kingdom
Hull Royal Infirmary
🇬🇧Hull, Yorkshire, United Kingdom
Aberdeen Royal Infirmary
🇬🇧Aberdeen, United Kingdom
North Middlesex University Hospital
🇬🇧London, United Kingdom
University Hospital
🇬🇧Coventry, Warwickshire, United Kingdom
St Mary's Hospital
🇬🇧London, United Kingdom
Broomfield Hospital
🇬🇧Chelmsford, Essex, United Kingdom
Wythenshawe Hospital
🇬🇧Manchester, Greater Manchester, United Kingdom
Worthing and Southlands Hospitals NHS Trust
🇬🇧Worthing, West Sussex, United Kingdom
Huddersfield Royal Infirmary
🇬🇧Huddersfield, West Yorkshire, United Kingdom
St James's University Hospital
🇬🇧Leeds, West Yorkshire, United Kingdom
Chelsea and Westminster Hospital
🇬🇧London, United Kingdom
Southmead Hospital
🇬🇧Bristol, Avon, United Kingdom
Royal Victoria Infirmary
🇬🇧Newcastle-Upon-Tyne, Tyne and Wear, United Kingdom
Calderdale Royal Hospital
🇬🇧Halifax, West Yorkshire, United Kingdom
Leicester General Hospital
🇬🇧Leicester, United Kingdom
Royal Halamshire Hospital
🇬🇧Sheffield, United Kingdom
The Great Western Hospital
🇬🇧Swindon, United Kingdom
Blackpool Victoria Hospital
🇬🇧Blackpool, Lancashire, United Kingdom
Homerton Hospital
🇬🇧London, United Kingdom
St Bartholomew's Hospital
🇬🇧London, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, Leicestershire, United Kingdom
Norfolk and Norwich University Hospitals
🇬🇧Norwich, Norfolk, United Kingdom
Kettering General Hospital
🇬🇧Kettering, Northants, United Kingdom
Frimley Park Hospital
🇬🇧Frimley, Surrey, United Kingdom
Glenfield Hospital
🇬🇧Leicester, United Kingdom
Castle Hill Hospital
🇬🇧Cottingham, East Riding of Yorkshire, United Kingdom
Charing Cross Hospital
🇬🇧London, United Kingdom