Biomarkers of Acute Serious Illness in Children

NCT03238040 | Completed

• 1 other identifier: 13SG19
• Study Type: observational
• Target: 674
• Locations: 1 country
• Sites: 4

Brief Summary

This study is a large multi-centre collaboration between a busy regional paediatric intensive care transport service (Children's Acute Transport Service, CATS), four large paediatric intensive care units (PICUs at Great Ormond Street Hospital, St Mary's Hospital and Royal London Hospital in London, and Addenbrookes Hospital in Cambridge) and the Department of Paediatrics at Imperial College, London. CATS transports over 800 sick children on life support to the three PICUs each year. We aim to improve our understanding of the genetic basis and biological pathways by which children with acute infection or injury become critically ill and develop failure of vital organs, and how these factors influence outcome. We will establish well-characterised cohorts of sick children with diverse pathologies, in whom blood, urine and other samples will be collected at an early stage of critical illness. Samples will be analysed using genomic, transcriptomic, proteomic and metabolomic approaches. Advanced bioinformatics techniques will be used to identify biomarkers for early diagnosis and robust risk stratification. We will focus on biomarkers to help distinguish between serious bacterial infections, viral infections and other causes of critical illness; diagnose incipient organ failure; and accurately identify, early on, children at high risk of developing a poor outcome. We will recruit critically ill children at first contact with the CATS team, during emergency transport to PICU. Due to the emergency nature of the research, and minimal risk associated with the study procedure, we will seek deferred, written informed consent from parents/guardians once their child has been stabilised, within 24-48 hours following PICU admission. By studying these important questions, we aim to better understand how we can diagnose and provide early life-saving treatments to critically ill children. The research team have an established track record of successful completion of several large clinical studies in critical care as well as validation of biomarkers in other diseases.

Conditions

Critical Illness; Infection, Mixed; Children, Only

Keywords

Critical illness; PICU; biomarkers

Outcome Measures

Primary Outcomes (3)

• Diagnosis of bacterial infection

  Diagnosis of a bacterial infection by laboratory tests (culture, molecular diagnostics)

  From recruitment until PICU discharge or up to 28 days, whichever occurs earlier

• Multiorgan failure

  Failure of two or more organs using the PELOD score

  From recruitment until PICU discharge or up to 28 days, whichever occurs earlier

• Poor outcome at intensive care unit discharge

  Mortality or development of severe disability

  From recruitment until PICU discharge or up to 28 days, whichever occurs earlier

Secondary Outcomes (2)

• Long term health related quality of life

  12 months after PICU discharge

• Long term behavioural outcome

  12 months after PICU discharge

Interventions

None, observational study OTHER

Observational study, no interventions

Eligibility Criteria

• Age: 0 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Critically ill children transported to an intensive care unit in an emergency

You may qualify if:

• Critically ill children aged 0-16 years requiring emergency transfer by the Children's Acute Transport Service (CATS) to participating paediatric intensive care units
• Presence of an indwelling catheter (arterial and/or venous) for blood sampling
• Presence of a urinary catheter for urine sample collection.

You may not qualify if:

• CATS transfers to other intensive care units or non-intensive care destination units
• Premature newborns (under 36 weeks corrected gestational age)
• Children with a known do-not-resuscitate (DNR) order in place.

Sponsors & Collaborators

• Great Ormond Street Hospital for Children NHS Foundation Trust: lead
• Imperial College London: collaborator
• Barts & The London NHS Trust: collaborator
• Imperial College Healthcare NHS Trust: collaborator
• University of Cambridge: collaborator

Study Sites (4)

Cambridge University Hospitals NHS Trust

Cambridge, United Kingdom

Location

Barts Health NHS Trust

London, United Kingdom

Location

Great Ormond Street Hospital for Children NHS Foundation Trust

London, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, United Kingdom

Location

Related Publications (3)

• Feinstein Y, Walker JC, Peters MJ, Nadel S, Pathan N, Edmonds N, Herberg J, Kaforou M, Wright V, Levin M, Ramnarayan P. Cohort profile of the Biomarkers of Acute Serious Illness in Children (BASIC) study: a prospective multicentre cohort study in critically ill children. BMJ Open. 2018 Nov 8;8(11):e024729. doi: 10.1136/bmjopen-2018-024729.

  PMID: 30413517 BACKGROUND

• Wijeyesekera A, Wagner J, De Goffau M, Thurston S, Rodrigues Sabino A, Zaher S, White D, Ridout J, Peters MJ, Ramnarayan P, Branco RG, Torok ME, Valla F, Meyer R, Klein N, Frost G, Parkhill J, Holmes E, Pathan N. Multi-Compartment Profiling of Bacterial and Host Metabolites Identifies Intestinal Dysbiosis and Its Functional Consequences in the Critically Ill Child. Crit Care Med. 2019 Sep;47(9):e727-e734. doi: 10.1097/CCM.0000000000003841.

  PMID: 31169619 RESULT

• Kean IRL, Wagner J, Wijeyesekera A, De Goffau M, Thurston S, Clark JA, White DK, Ridout J, Agrawal S, Kayani R, O'Donnell R, Ramnarayan P, Peters MJ, Klein N, Holmes E, Parkhill J, Baker S, Pathan N. Profiling gut microbiota and bile acid metabolism in critically ill children. Sci Rep. 2022 Jun 21;12(1):10432. doi: 10.1038/s41598-022-13640-0.

  PMID: 35729169 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Blood in EDTA tube (DNA), PAX gene tube (RNA), Plasma, Serum (5 ml in total, or 0.8 ml/kg whichever is lower) Urine in universal container (5-10 ml)

MeSH Terms

Conditions

Critical Illness; Coinfection

Interventions

Observation

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Padmanabhan Ramnarayan

  Children's Acute Transport Service, Great Ormond Street Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2017
• First Posted: August 3, 2017
• Study Start: April 1, 2014
• Primary Completion: December 31, 2017
• Study Completion: December 31, 2017
• Last Updated: October 4, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (4)