Functional Genomic Influences on Disease Progression and Outcome in Sepsis

NCT00131196 | Unknown DMC

• 1 other identifier: N8518
• Study Type: observational
• Target: 4,000
• Locations: 1 country
• Sites: 50

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.

Conditions

Pneumonia; Peritonitis

Keywords

pneumonia; peritonitis; sepsis; outcome; genomics

Outcome Measures

Primary Outcomes (1)

• ICU and hospital Mortality

  ICU discharge, hospital discharge and 6 month. The date of death will be recorded, as appropriate, for each patient.

Secondary Outcomes (1)

• Severity of illness, duration of organ support, shock reversal, duration of ICU and hospital stay

  From ICU admission to discharge

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Oxford: lead
• Sainsbury Family Charitable Trusts: collaborator
• Wellcome Trust: collaborator
• Queen Mary University of London: collaborator
• Barts and the London School of Medicine and Dentistry: collaborator

Study Sites (50)

Southmead Hospital

Bristol, Avon, BS10 5NB, United Kingdom

COMPLETED

Royal Berkshire Hospital

Reading, Berkshire, RG1 5AN, United Kingdom

RECRUITING

Addenbrooke's Hospital

Cambridge, Cambridgeshire, CB2 2QQ, United Kingdom

COMPLETED

James Cook University Hospital

Middlesbrough, Cleveland, TS4 3BW, United Kingdom

COMPLETED

Antrim Hospital

Antrim, County Antrim, BT41 2RL, United Kingdom

COMPLETED

Castle Hill Hospital

Cottingham, East Riding of Yorkshire, HU16 5JQ, United Kingdom

COMPLETED

Broomfield Hospital

Chelmsford, Essex, CM1 7ET, United Kingdom

COMPLETED

Colchester General Hospital

Colchester, Essex, CO4 5JL, United Kingdom

COMPLETED

Southend General Hospital

Southend, Essex, SS0 0RY, United Kingdom

COMPLETED

Bristol Royal Infirmary

Bristol, Gloucestershire, BS2 8HW, United Kingdom

COMPLETED

Cheltenham General Hospital

Cheltenham, Gloucestershire, GL53 7AN, United Kingdom

COMPLETED

Withington Hospital

Manchester, Greater Manchester, M20 2LR, United Kingdom

COMPLETED

Wythenshawe Hospital

Manchester, Greater Manchester, M23 9LT, United Kingdom

COMPLETED

Hope Hospital

Manchester, Greater Manchester, M6 8HD, United Kingdom

COMPLETED

Royal Blackburn Hospital

Blackburn, Lancashire, BB2 3HH, United Kingdom

COMPLETED

Blackpool Victoria Hospital

Blackpool, Lancashire, FY3 8NR, United Kingdom

COMPLETED

Royal Preston Hospital

Preston, Lancashire, PR2 9HT, United Kingdom

COMPLETED

Leicester Royal Infirmary

Leicester, Leicestershire, LE1 5WW, United Kingdom

RECRUITING

University Hospital Lewisham

Lewisham, London, SE13 6LH, United Kingdom

COMPLETED

Queen Elizabeth Hospital

Kings Lynn, Norfolk, PE30 4ET, United Kingdom

COMPLETED

Norfolk and Norwich University Hospitals

Norwich, Norfolk, NR4 7UZ, United Kingdom

COMPLETED

Kettering General Hospital

Kettering, Northants, NN16 8UZ, United Kingdom

COMPLETED

John Radcliffe Hospital

Oxford, Oxon, OX3 9DU, United Kingdom

RECRUITING

University Hospital of Wales

Cardiff, South Glamorgan, CF14 4XW, United Kingdom

COMPLETED

Frenchay Hospital

Bristol, South Gloucestershire, BS16 1LE, United Kingdom

COMPLETED

The Ipswich Hospital

Ipswich, Suffolk, IP4 5PD, United Kingdom

COMPLETED

Frimley Park Hospital

Frimley, Surrey, GU16 7UJ, United Kingdom

COMPLETED

Royal Sussex County Hospital

Brighton, Sussex, BN2 5BE, United Kingdom

COMPLETED

Royal Victoria Infirmary

Newcastle upon Tyne, Tyne and Wear, NE1 4LP, United Kingdom

COMPLETED

University Hospital

Coventry, Warwickshire, CV2 2DX, United Kingdom

COMPLETED

Queen Elizabeth Hospital

Birmingham, West Midlands, B15 2TH, United Kingdom

RECRUITING

Walsall Manor Hospital

Walsall, West Midlands, WS2 9PS, United Kingdom

COMPLETED

Worthing and Southlands Hospitals NHS Trust

Worthing, West Sussex, BN11 2DH, United Kingdom

COMPLETED

Calderdale Royal Hospital

Halifax, West Yorkshire, HX3 0PW, United Kingdom

COMPLETED

Huddersfield Royal Infirmary

Huddersfield, West Yorkshire, HD3 3EA, United Kingdom

COMPLETED

St James's University Hospital

Leeds, West Yorkshire, LS9 7TF, United Kingdom

COMPLETED

Hull Royal Infirmary

Hull, Yorkshire, HU3 2JZ, United Kingdom

COMPLETED

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZN, United Kingdom

COMPLETED

Glenfield Hospital

Leicester, LE3 9QP, United Kingdom

RECRUITING

Leicester General Hospital

Leicester, LE5 4PW, United Kingdom

RECRUITING

Homerton Hospital

London, E9 6SR, United Kingdom

COMPLETED

St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

RECRUITING

North Middlesex University Hospital

London, N18 1QX, United Kingdom

COMPLETED

Chelsea and Westminster Hospital

London, SW10 9NH, United Kingdom

COMPLETED

Hammersmith Hospital

London, W12 0HS, United Kingdom

COMPLETED

UCLH Middlesex Hospital

London, W1T 3AA, United Kingdom

COMPLETED

St Mary's Hospital

London, W2 1NY, United Kingdom

COMPLETED

Charing Cross Hospital

London, W6 8RF, United Kingdom

COMPLETED

Royal Halamshire Hospital

Sheffield, S10 2JF, United Kingdom

COMPLETED

The Great Western Hospital

Swindon, SN3 6BB, United Kingdom

COMPLETED

Related Publications (9)

• Vincent JL, Angus D, Annane D, Bernard G, Faist E, Giroir B, Reinhart K. Clinical expert round table discussion (session 5) at the Margaux Conference on Critical Illness: outcomes of clinical trials in sepsis: lessons learned. Crit Care Med. 2001 Jul;29(7 Suppl):S136-7. doi: 10.1097/00003246-200107001-00040. No abstract available.

  PMID: 11445749 BACKGROUND

• Brun-Buisson C, Doyon F, Carlet J, Dellamonica P, Gouin F, Lepoutre A, Mercier JC, Offenstadt G, Regnier B. Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis. JAMA. 1995 Sep 27;274(12):968-74.

  PMID: 7674528 BACKGROUND

• File TM. Community-acquired pneumonia. Lancet. 2003 Dec 13;362(9400):1991-2001. doi: 10.1016/S0140-6736(03)15021-0.

  PMID: 14683661 BACKGROUND

• Gordon AC, Lagan AL, Aganna E, Cheung L, Peters CJ, McDermott MF, Millo JL, Welsh KI, Holloway P, Hitman GA, Piper RD, Garrard CS, Hinds CJ. TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study. Genes Immun. 2004 Dec;5(8):631-40. doi: 10.1038/sj.gene.6364136.

  PMID: 15526005 BACKGROUND

• Mira JP, Cariou A, Grall F, Delclaux C, Losser MR, Heshmati F, Cheval C, Monchi M, Teboul JL, Riche F, Leleu G, Arbibe L, Mignon A, Delpech M, Dhainaut JF. Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study. JAMA. 1999 Aug 11;282(6):561-8. doi: 10.1001/jama.282.6.561.

  PMID: 10450718 BACKGROUND

• Sands KE, Bates DW, Lanken PN, Graman PS, Hibberd PL, Kahn KL, Parsonnet J, Panzer R, Orav EJ, Snydman DR, Black E, Schwartz JS, Moore R, Johnson BL Jr, Platt R; Academic Medical Center Consortium Sepsis Project Working Group. Epidemiology of sepsis syndrome in 8 academic medical centers. JAMA. 1997 Jul 16;278(3):234-40.

  PMID: 9218672 BACKGROUND

• Sorensen TI, Nielsen GG, Andersen PK, Teasdale TW. Genetic and environmental influences on premature death in adult adoptees. N Engl J Med. 1988 Mar 24;318(12):727-32. doi: 10.1056/NEJM198803243181202.

  PMID: 3347221 BACKGROUND

• Roy S, Knox K, Segal S, Griffiths D, Moore CE, Welsh KI, Smarason A, Day NP, McPheat WL, Crook DW, Hill AV; Oxford Pneumoccocal Surveillance Group. MBL genotype and risk of invasive pneumococcal disease: a case-control study. Lancet. 2002 May 4;359(9317):1569-73. doi: 10.1016/S0140-6736(02)08516-1.

  PMID: 12047967 BACKGROUND

• Scicluna BP, Cano-Gamez K, Burnham KL, Davenport EE, Moore AR, Khan S, Hinds CJ, Cremer OL, Khatri P, Sweeney TE, Knight JC, van der Poll T. A consensus blood transcriptomic framework for sepsis. Nat Med. 2025 Dec;31(12):4119-4130. doi: 10.1038/s41591-025-03964-5. Epub 2025 Sep 30.

  PMID: 41028542 DERIVED

Related Links

• GAinS Website (Genomic Advances in Sepsis)

Biospecimen

Retention: SAMPLES WITH DNA

whole blood, plasma and extracted DNA

MeSH Terms

Conditions

Pneumonia; Peritonitis; Sepsis

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Intraabdominal Infections; Peritoneal Diseases; Digestive System Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• 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

  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 Hospitals NHS Trust

  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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charles J Hinds, MD

CONTACT

+44 20346 57294; c.j.hinds@qmul.ac.uk

Christopher S Garrard, MD PhD

CONTACT

+44 1865 220621; chris.garrard@ndm.ox.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant in Intensive care

Study Record Dates

• First Submitted: August 15, 2005
• First Posted: August 17, 2005
• Study Start: September 1, 2005
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: May 16, 2016

Record last verified: 2016-05

Locations

GB (50)