Personalised Risk Assessment in Febrile Illness to Optimise Real-life Management Across the European Union (PERFORM)

NCT03502993 | Completed Results

• 2 other identifiers: REC ref: 16/LO/1684BIVA studies
• Study Type: observational
• Target: 7,247
• Locations: 1 country
• Sites: 1

Brief Summary

Childhood fever is a prevalent problem. Most febrile children who visit hospital improve without treatment, but a minority require treatment, and a few will have severe disease. The investigators want to improve the diagnosis and management of febrile children by developing tests to distinguish between bacterial and viral disease so that antibiotic treatment can be initiated promptly and only when required. Judicious and prudent use of antibiotics will reduce the likelihood of developing resistant organisms and save treatment costs. The investigators will prospectively recruit acutely febrile children presenting to hospital, collecting research samples for validation of biomarkers, in combination with clinical phenotypic markers and host genetic markers (BIVA-studies). Any febrile child newborn to under 18 presenting to hospital will be eligible for recruitment. The study will last 5 years.

Conditions

Fever; Infection; Inflammation

Keywords

children

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Clinically-assigned Retrospective Phenotype

  Clinically-assigned retrospective phenotype, according to the cause of illness

  Participants were monitored for outcome throughout their stay in hospital, and received follow-up review at 10 days

Study Arms (2)

BIVA studies - children with fever and/or suspected infection

A minimum of 3,000 children will be recruited to the BIVA-ED (Biomarker Validation in Emergency Department) study, in order to capture sufficient children with confirmed bacterial infection. Additional children with less common febrile illnesses will also be recruited: 500 critically ill (BIVA-PIC); 200 at high-risk of bacterial illness through primary or secondary immunodeficiency (BIVA-HR); 150 with an inflammatory diagnosis, whose initial presentation is difficult to discriminate from bacterial infection (BIVA-INF). Samples collected from recruits in the BIVA studies will be used for the validation of biomarkers (clinical, proteomic and transcriptomic biomarkers) for diagnosis of febrile illness, including markers of bacterial and viral infection (confirmed by culture and/or molecular microbiology) and inflammatory conditions.

Diagnostic Test: Validation of biomarker

BIVA studies - control children without fever or suspicion of infection

Afebrile children \<18 years (16 years depending in the setting) of age who are having blood tests for reasons other than for investigation of infectious or inflammatory illness or whom parents give consent for bloods taken for research purposes. Controls may have a range of clinical presentations including co-morbidities without infection. One set of samples will be taken from controls, no follow up data or samples taken.

Diagnostic Test: Validation of biomarker

Interventions

Validation of biomarker DIAGNOSTIC_TEST

BIVA studies - children with fever and/or suspected infection; BIVA studies - control children without fever or suspicion of infection

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Children with fever \>38ºC, or a history of fever (within 3 days) who requires a blood test for clinical reasons or consents for research bloods to be taken,

You may qualify if:

• All children \<18 years with fever \>38ºC, or a history of fever (within 3 days), in whom the attending clinician determines the need for blood sampling or whom parents give consent for bloods taken for research purposes
• All children \<18 years suspected of infection, including the full spectrum of disease severity and co-morbidities.
• Afebrile control children who are having blood tests for reasons other than for investigation of infectious or inflammatory illness.

You may not qualify if:

• Children from whom parent/legal guardian signed consent is not received
• For healthy control children only: febrile illness or vaccination within the last 3 weeks.

Sponsors & Collaborators

• Imperial College London: lead
• London School of Hygiene and Tropical Medicine: collaborator
• University of Liverpool: collaborator
• University of Newcastle Upon-Tyne: collaborator
• Erasmus Medical Center: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• National and Kapodistrian University of Athens: collaborator
• Stichting Katholieke Universiteit: collaborator
• University of Graz: collaborator
• University of Ljubljana: collaborator
• Riga Stradins University: collaborator
• Medical Research Council Unit, The Gambia: collaborator
• Ludwig-Maximilians - University of Munich: collaborator
• University of Bern: collaborator
• University of Oxford: collaborator
• University Hospital, Paris: collaborator
• University of Santiago de Compostela: collaborator
• Servicio Gallego de Salud: collaborator
• BioMérieux: collaborator
• Micropathology Ltd, University of Warwick: collaborator

Study Sites (1)

Imperial College London

London, W2 1PG, United Kingdom

Location

Related Publications (2)

• Habgood-Coote D, Wilson C, Shimizu C, Barendregt AM, Philipsen R, Galassini R, Calle IR, Workman L, Agyeman PKA, Ferwerda G, Anderson ST, van den Berg JM, Emonts M, Carrol ED, Fink CG, de Groot R, Hibberd ML, Kanegaye J, Nicol MP, Paulus S, Pollard AJ, Salas A, Secka F, Schlapbach LJ, Tremoulet AH, Walther M, Zenz W; Pediatric Emergency Medicine Kawasaki Disease Research Group (PEMKDRG); UK Kawasaki Genetics consortium; GENDRES consortium; EUCLIDS consortium; PERFORM consortium; Van der Flier M, Zar HJ, Kuijpers T, Burns JC, Martinon-Torres F, Wright VJ, Coin LJM, Cunnington AJ, Herberg JA, Levin M, Kaforou M. Diagnosis of childhood febrile illness using a multi-class blood RNA molecular signature. Med. 2023 Sep 8;4(9):635-654.e5. doi: 10.1016/j.medj.2023.06.007. Epub 2023 Aug 18.

  PMID: 37597512 RESULT

• Hartman SJF, Upadhyay PJ, Hagedoorn NN, Mathot RAA, Moll HA, van der Flier M, Schreuder MF, Bruggemann RJ, Knibbe CA, de Wildt SN. Current Ceftriaxone Dose Recommendations are Adequate for Most Critically Ill Children: Results of a Population Pharmacokinetic Modeling and Simulation Study. Clin Pharmacokinet. 2021 Oct;60(10):1361-1372. doi: 10.1007/s40262-021-01035-9. Epub 2021 May 26.

  PMID: 34036552 DERIVED

Related Links

• publications and conference proceedings pertaining to PERFORM - BIVA studies

Biospecimen

Retention: SAMPLES WITH DNA

blood, urine, nasopharyngeal aspirate/throat swab, stool

MeSH Terms

Conditions

Fever; Infections; Inflammation

Condition Hierarchy (Ancestors)

Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Results Point of Contact

• Title: Dr J Herberg
• Organization: Imperial College London

j.herberg@imperial.ac.uk

0207 594 3900

Study Officials

• Michael Levin

  Imperial College London

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: March 27, 2018
• First Posted: April 19, 2018
• Study Start: June 2, 2016
• Primary Completion: January 25, 2021
• Study Completion: December 31, 2021
• Last Updated: October 13, 2023
• Results First Posted: October 13, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)