Functional Genomic Influences on Disease Progression and Outcome in Sepsis (GAinS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 by University of Oxford
Sponsor:
Collaborators:
Sainsbury Family Charitable Trusts
Wellcome Trust Centre for Human Genetics, Oxford
Queen Mary University of London
Barts and the London School of Medicine and Dentistry
Information provided by (Responsible Party):
Dr CS Garrard, University of Oxford
ClinicalTrials.gov Identifier:
NCT00131196
First received: August 15, 2005
Last updated: February 5, 2015
Last verified: February 2015
  Purpose

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.


Condition
Pneumonia
Peritonitis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Functional Genomic Influences on Disease Progression and Outcome in Sepsis Due to Pneumonia or Peritonitis

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • ICU and hospital Mortality [ Time Frame: ICU discharge, hospital discharge and 6 month. The date of death will be recorded, as appropriate, for each patient. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Severity of illness, duration of organ support, shock reversal, duration of ICU and hospital stay [ Time Frame: From ICU admission to discharge ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

whole blood, plasma and extracted DNA


Estimated Enrollment: 4000
Study Start Date: September 2005
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients admitted to Intensive Care Units or High Dependency Units in the UK with faecal peritonitis or community acquired pneumonia

Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00131196

Contacts
Contact: Charles J Hinds, MD +44 20346 57294 c.j.hinds@qmul.ac.uk
Contact: Christopher S Garrard, MD PhD +44 1865 220621 chris.garrard@ndm.ox.ac.uk

  Show 50 Study Locations
Sponsors and Collaborators
University of Oxford
Sainsbury Family Charitable Trusts
Wellcome Trust Centre for Human Genetics, Oxford
Queen Mary University of London
Barts and the London School of Medicine and Dentistry
Investigators
Principal Investigator: Christopher S Garrard, MD PhD University of Oxford, UK
Principal Investigator: Charles J Hinds, MD Queen Mary College, University of London, UK
Principal Investigator: Simon Baudouin, MD Royal Victoria Infirmary and Freeman Hospital, Newcastle, UK
Principal Investigator: David Higgins, MD Southend General Hospital, Southend, UK.
Principal Investigator: Richard Venn, MD Worthing and Southlands Hospitals NHS Trust, Worthing, UK.
Principal Investigator: David Watson, MD Homerton University Hospital, London, UK.
Principal Investigator: Atul Kapila, MD Royal Berkshire Hospital, Reading, UK.
Principal Investigator: Simon Fletcher, MD Norfolk and Norwich University Hospitals, Norwich, UK.
Principal Investigator: Andrew Johnston, MD Addenbrooke's Hospital, Cambridge, UK.
Principal Investigator: Julian Bion, Professor Queen Elizabeth Hospital, Birmingham, UK.
Principal Investigator: Gary Mills, MD Royal Halamshire Hospital, Sheffield, UK.
Principal Investigator: Stephen Bonner, MD James Cook University Hospital, Middlesborough, UK.
Principal Investigator: Mark Garfield, MD The Ipswich Hospital, Ipswich, UK.
Principal Investigator: Ronald Baillie, MD Antrim Hospital, Antrim, Northern Ireland.
Principal Investigator: George Findlay, MD University Hospital of Wales, Cardiff,UK.
Principal Investigator: Geoffrey Bellingan, MD UCLH Middlesex Hospital, London, UK.
Principal Investigator: Tony Gordon, MD Charing Cross Hospital, London, UK.
Principal Investigator: Michelle Hayes, MD Chelsea and Westminster Hospital, London, UK.
Principal Investigator: Dilshan Arawwawala, MD Broomfield Hospital, Chelmsford, UK.
Principal Investigator: Andrew Bentley, MD Wythenshawe Hospital, Manchester, UK.
Principal Investigator: Gareth Thomas, MD Hope Hospital, Manchester, UK.
Principal Investigator: Julian Knight, MD Wellcome Trust Centre for Human Genetics, Oxford
Principal Investigator: Jonathan Thompson, MD University Hospitals, Leicester
Principal Investigator: Jasmeet Soar, MD Frenchay Hospital and Southmead Hospital, Bristol
Principal Investigator: Phil Watt, MD Kettering General Hospital
Principal Investigator: Anton Krige, MD Royal Blackburn Hospital
Principal Investigator: Ian Smith, MD Castle Hill Hospital and Hull Royal Infirmary
Principal Investigator: Achyut Guleri, MD Blackpool Victoria Hospital
Principal Investigator: Shond Laha, MD Royal Preston Hospital
Principal Investigator: Stephen Brett, MD Hammersmith Hospital
Principal Investigator: Jeronimo Moreno Cuesta, MD North Middlesex University Hospital
Principal Investigator: Pyda Venkatesh, MD Coventry University Hospital
Principal Investigator: Peter Hall, MD Huddersfield Royal Infirmary and Calderdale Royal Hospital
Principal Investigator: Martin Kuper, MD The WhittingtonHospital, London. UK
Principal Investigator: Sia Pesian, MD Manor Hospital, Walsall. UK
Principal Investigator: Andrew Timmins, MD Colchester Hospital, Colchester . UK
Principal Investigator: Stephen Drage, MD Royal Sussex County Hospital
Principal Investigator: Martin Stotz, MD St Mary's Hospital, London. UK
Principal Investigator: Mark Blunt, MD Queen Elizabeth Hospital, King's Lynn. UK
Principal Investigator: Nigel Webster, Professor Aberdeen Royal Infirmary
Principal Investigator: Jane Minton, MD St James Hospital, Leeds. UK
Principal Investigator: Matt Oram, MD Cheltenham General Hospital, Cheltenham. UK
Principal Investigator: Ingrid Krupe, MD Lewisham Hospital
Principal Investigator: Abhiram Mallick, MD Leeds General Infirmary, Leeds. UK
Principal Investigator: Samuel Pambakian, MD Frimley Park Hospital, Frimley. UK
Principal Investigator: Malcolm Watters, MD Great Western Hospital, Swindon. UK
  More Information

Publications:

Responsible Party: Dr CS Garrard, Consultant in Intensive care, University of Oxford
ClinicalTrials.gov Identifier: NCT00131196     History of Changes
Other Study ID Numbers: N8518
Study First Received: August 15, 2005
Last Updated: February 5, 2015
Health Authority: United Kingdom: National Health Service

Keywords provided by University of Oxford:
pneumonia
peritonitis
sepsis
outcome
genomics

Additional relevant MeSH terms:
Peritonitis
Disease Progression
Pneumonia
Digestive System Diseases
Disease Attributes
Infection
Intraabdominal Infections
Lung Diseases
Pathologic Processes
Peritoneal Diseases
Respiratory Tract Diseases
Respiratory Tract Infections

ClinicalTrials.gov processed this record on April 27, 2015