Functional Genomic Influences on Disease Progression and Outcome in Sepsis

NCT ID: NCT00131196

Last Updated: 2016-05-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

4000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2005-09-30

Study Completion Date

2017-12-31

Brief Summary

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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

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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.

Conditions

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Pneumonia Peritonitis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sainsbury Family Charitable Trusts

OTHER

Sponsor Role collaborator

Wellcome Trust

OTHER

Sponsor Role collaborator

Queen Mary University of London

OTHER

Sponsor Role collaborator

Barts and the London School of Medicine and Dentistry

OTHER

Sponsor Role collaborator

University of Oxford

OTHER

Sponsor Role lead

Responsible Party

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Dr CS Garrard

Consultant in Intensive care

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Christopher S Garrard, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University of Oxford, UK

Charles J Hinds, MD

Role: PRINCIPAL_INVESTIGATOR

Queen Mary College, University of London, UK

Simon Baudouin, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Victoria Infirmary and Freeman Hospital, Newcastle, UK

David Higgins, MD

Role: PRINCIPAL_INVESTIGATOR

Southend General Hospital, Southend, UK.

Richard Venn, MD

Role: PRINCIPAL_INVESTIGATOR

Worthing and Southlands Hospitals NHS Trust, Worthing, UK.

David Watson, MD

Role: PRINCIPAL_INVESTIGATOR

Homerton University Hospital, London, UK.

Atul Kapila, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Berkshire Hospital, Reading, UK.

Simon Fletcher, MD

Role: PRINCIPAL_INVESTIGATOR

Norfolk and Norwich University Hospitals, Norwich, UK.

Andrew Johnston, MD

Role: PRINCIPAL_INVESTIGATOR

Addenbrooke's Hospital, Cambridge, UK.

Julian Bion, Professor

Role: PRINCIPAL_INVESTIGATOR

Queen Elizabeth Hospital, Birmingham, UK.

Gary Mills, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Halamshire Hospital, Sheffield, UK.

Stephen Bonner, MD

Role: PRINCIPAL_INVESTIGATOR

James Cook University Hospital, Middlesborough, UK.

Mark Garfield, MD

Role: PRINCIPAL_INVESTIGATOR

The Ipswich Hospital, Ipswich, UK.

Ronald Baillie, MD

Role: PRINCIPAL_INVESTIGATOR

Antrim Hospital, Antrim, Northern Ireland.

George Findlay, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Wales, Cardiff,UK.

Geoffrey Bellingan, MD

Role: PRINCIPAL_INVESTIGATOR

UCLH Middlesex Hospital, London, UK.

Tony Gordon, MD

Role: PRINCIPAL_INVESTIGATOR

Charing Cross Hospital, London, UK.

Michelle Hayes, MD

Role: PRINCIPAL_INVESTIGATOR

Chelsea and Westminster Hospital, London, UK.

Dilshan Arawwawala, MD

Role: PRINCIPAL_INVESTIGATOR

Broomfield Hospital, Chelmsford, UK.

Andrew Bentley, MD

Role: PRINCIPAL_INVESTIGATOR

Wythenshawe Hospital, Manchester, UK.

Gareth Thomas, MD

Role: PRINCIPAL_INVESTIGATOR

Hope Hospital, Manchester, UK.

Julian Knight, MD

Role: PRINCIPAL_INVESTIGATOR

Wellcome Trust

Jonathan Thompson, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospitals, Leicester

Jasmeet Soar, MD

Role: PRINCIPAL_INVESTIGATOR

Frenchay Hospital and Southmead Hospital, Bristol

Phil Watt, MD

Role: PRINCIPAL_INVESTIGATOR

Kettering General Hospital

Anton Krige, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Blackburn Hospital

Ian Smith, MD

Role: PRINCIPAL_INVESTIGATOR

Castle Hill Hospital and Hull Royal Infirmary

Achyut Guleri, MD

Role: PRINCIPAL_INVESTIGATOR

Blackpool Victoria Hospital

Shond Laha, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Preston Hospital

Stephen Brett, MD

Role: PRINCIPAL_INVESTIGATOR

Hammersmith Hospitals NHS Trust

Jeronimo Moreno Cuesta, MD

Role: PRINCIPAL_INVESTIGATOR

North Middlesex University Hospital

Pyda Venkatesh, MD

Role: PRINCIPAL_INVESTIGATOR

Coventry University Hospital

Peter Hall, MD

Role: PRINCIPAL_INVESTIGATOR

Huddersfield Royal Infirmary and Calderdale Royal Hospital

Martin Kuper, MD

Role: PRINCIPAL_INVESTIGATOR

The WhittingtonHospital, London. UK

Sia Pesian, MD

Role: PRINCIPAL_INVESTIGATOR

Manor Hospital, Walsall. UK

Andrew Timmins, MD

Role: PRINCIPAL_INVESTIGATOR

Colchester Hospital, Colchester . UK

Stephen Drage, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Sussex County Hospital

Martin Stotz, MD

Role: PRINCIPAL_INVESTIGATOR

St. Mary's Hospital, London, UK

Mark Blunt, MD

Role: PRINCIPAL_INVESTIGATOR

Queen Elizabeth Hospital, King's Lynn. UK

Nigel Webster, Professor

Role: PRINCIPAL_INVESTIGATOR

Aberdeen Royal Infirmary

Jane Minton, MD

Role: PRINCIPAL_INVESTIGATOR

St James Hospital, Leeds. UK

Matt Oram, MD

Role: PRINCIPAL_INVESTIGATOR

Cheltenham General Hospital, Cheltenham. UK

Ingrid Krupe, MD

Role: PRINCIPAL_INVESTIGATOR

Lewisham Hospital

Abhiram Mallick, MD

Role: PRINCIPAL_INVESTIGATOR

Leeds General Infirmary, Leeds. UK

Samuel Pambakian, MD

Role: PRINCIPAL_INVESTIGATOR

Frimley Park Hospital, Frimley. UK

Malcolm Watters, MD

Role: PRINCIPAL_INVESTIGATOR

Great Western Hospital, Swindon. UK

Locations

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Southmead Hospital

Bristol, Avon, United Kingdom

Site Status COMPLETED

Royal Berkshire Hospital

Reading, Berkshire, United Kingdom

Site Status RECRUITING

Addenbrooke's Hospital

Cambridge, Cambridgeshire, United Kingdom

Site Status COMPLETED

James Cook University Hospital

Middlesbrough, Cleveland, United Kingdom

Site Status COMPLETED

Antrim Hospital

Antrim, County Antrim, United Kingdom

Site Status COMPLETED

Castle Hill Hospital

Cottingham, East Riding of Yorkshire, United Kingdom

Site Status COMPLETED

Broomfield Hospital

Chelmsford, Essex, United Kingdom

Site Status COMPLETED

Colchester General Hospital

Colchester, Essex, United Kingdom

Site Status COMPLETED

Southend General Hospital

Southend, Essex, United Kingdom

Site Status COMPLETED

Bristol Royal Infirmary

Bristol, Gloucestershire, United Kingdom

Site Status COMPLETED

Cheltenham General Hospital

Cheltenham, Gloucestershire, United Kingdom

Site Status COMPLETED

Withington Hospital

Manchester, Greater Manchester, United Kingdom

Site Status COMPLETED

Wythenshawe Hospital

Manchester, Greater Manchester, United Kingdom

Site Status COMPLETED

Hope Hospital

Manchester, Greater Manchester, United Kingdom

Site Status COMPLETED

Royal Blackburn Hospital

Blackburn, Lancashire, United Kingdom

Site Status COMPLETED

Blackpool Victoria Hospital

Blackpool, Lancashire, United Kingdom

Site Status COMPLETED

Royal Preston Hospital

Preston, Lancashire, United Kingdom

Site Status COMPLETED

Leicester Royal Infirmary

Leicester, Leicestershire, United Kingdom

Site Status RECRUITING

University Hospital Lewisham

Lewisham, London, United Kingdom

Site Status COMPLETED

Queen Elizabeth Hospital

Kings Lynn, Norfolk, United Kingdom

Site Status COMPLETED

Norfolk and Norwich University Hospitals

Norwich, Norfolk, United Kingdom

Site Status COMPLETED

Kettering General Hospital

Kettering, Northants, United Kingdom

Site Status COMPLETED

John Radcliffe Hospital

Oxford, Oxon, United Kingdom

Site Status RECRUITING

University Hospital of Wales

Cardiff, South Glamorgan, United Kingdom

Site Status COMPLETED

Frenchay Hospital

Bristol, South Gloucestershire, United Kingdom

Site Status COMPLETED

The Ipswich Hospital

Ipswich, Suffolk, United Kingdom

Site Status COMPLETED

Frimley Park Hospital

Frimley, Surrey, United Kingdom

Site Status COMPLETED

Royal Sussex County Hospital

Brighton, Sussex, United Kingdom

Site Status COMPLETED

Royal Victoria Infirmary

Newcastle upon Tyne, Tyne and Wear, United Kingdom

Site Status COMPLETED

University Hospital

Coventry, Warwickshire, United Kingdom

Site Status COMPLETED

Queen Elizabeth Hospital

Birmingham, West Midlands, United Kingdom

Site Status RECRUITING

Walsall Manor Hospital

Walsall, West Midlands, United Kingdom

Site Status COMPLETED

Worthing and Southlands Hospitals NHS Trust

Worthing, West Sussex, United Kingdom

Site Status COMPLETED

Calderdale Royal Hospital

Halifax, West Yorkshire, United Kingdom

Site Status COMPLETED

Huddersfield Royal Infirmary

Huddersfield, West Yorkshire, United Kingdom

Site Status COMPLETED

St James's University Hospital

Leeds, West Yorkshire, United Kingdom

Site Status COMPLETED

Hull Royal Infirmary

Hull, Yorkshire, United Kingdom

Site Status COMPLETED

Aberdeen Royal Infirmary

Aberdeen, , United Kingdom

Site Status COMPLETED

Glenfield Hospital

Leicester, , United Kingdom

Site Status RECRUITING

Leicester General Hospital

Leicester, , United Kingdom

Site Status RECRUITING

Homerton Hospital

London, , United Kingdom

Site Status COMPLETED

St Bartholomew's Hospital

London, , United Kingdom

Site Status RECRUITING

North Middlesex University Hospital

London, , United Kingdom

Site Status COMPLETED

Chelsea and Westminster Hospital

London, , United Kingdom

Site Status COMPLETED

Hammersmith Hospital

London, , United Kingdom

Site Status COMPLETED

UCLH Middlesex Hospital

London, , United Kingdom

Site Status COMPLETED

St Mary's Hospital

London, , United Kingdom

Site Status COMPLETED

Charing Cross Hospital

London, , United Kingdom

Site Status COMPLETED

Royal Halamshire Hospital

Sheffield, , United Kingdom

Site Status COMPLETED

The Great Western Hospital

Swindon, , United Kingdom

Site Status COMPLETED

Countries

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United Kingdom

Central Contacts

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Charles J Hinds, MD

Role: CONTACT

+44 20346 57294

Christopher S Garrard, MD PhD

Role: CONTACT

+44 1865 220621

Facility Contacts

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Atul Kapila, MD

Role: primary

0118 9875111

Jonathan Thompson, MD

Role: primary

0300 303 1573

Christopher Garrard, MD

Role: primary

01865 220621

Julian Bion, MD

Role: primary

0121 627 1627

Jonathan Thompson, MD

Role: primary

0300 303 1573

Jonathon Thompson, MD

Role: primary

Charles Hinds, MD

Role: primary

020 7377 7000

References

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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.

Reference Type BACKGROUND
PMID: 11445749 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7674528 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 14683661 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15526005 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10450718 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9218672 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3347221 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12047967 (View on PubMed)

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 Sep 30. doi: 10.1038/s41591-025-03964-5. Online ahead of print.

Reference Type DERIVED
PMID: 41028542 (View on PubMed)

Related Links

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http://www.ukccg-gains.org/

GAinS Website (Genomic Advances in Sepsis)

Other Identifiers

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N8518

Identifier Type: -

Identifier Source: org_study_id

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