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

Inflammation Clinical Trial

— PERFORM  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03502993
• Other study ID #: REC ref: 16/LO/1684
• Secondary ID: BIVA studies
• Status: Completed
• Start date: June 2, 2016
• Est. completion date: December 31, 2021

Study information

• Verified date: October 2023
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

The problem to be addressed:

Fever is among the commonest symptoms for which parents consult health care providers worldwide. Distinction between life-threatening bacterial infection and viral infection is clinically difficult, and many children worldwide receive unnecessary antibiotic treatment, or undergo invasive investigations and hospitalization, whilst bacterial infection is missed in others.

Objective:

The investigators aim to validate biomarkers that will identify children with bacterial infection, viral infection and inflammatory syndromes, using whole-blood RNA expression, proteomic and metabolomics signatures. The investigators aim to assess how efficacious these biomarkers would be if they formed the basis of a diagnostic test.

Design:

The investigators will use established case-control groups of febrile children presenting to hospital, recruited across Europe as part of previous (and current) ethically-approved studies, to discover signatures of febrile illness. The investigators will validate these signatures in samples prospectively collected from children as part of this observational study.

The investigators will use prospective, observational BIVA studies to recruit febrile children with infectious and inflammatory diseases in order to validate diagnostic biomarkers. The investigators will also recruit non-febrile controls in order to discover and validate disease-specific biomarkers and to understand their biological significance.

STUDY SIZE at least 4000 febrile children;

PROCEDURES;

Informed consent using age appropriate patient/parent/guardian information sheets will be taken from parents (or from children aged 16 and over), assent will be taken from the child under the age of 16 (if appropriate).

Routine clinical and laboratory data and research samples from three timepoints (presentation, 48 hours after presentation, 28 days after admission). If patients present to hospital with fever on subsequent occasions, clinical data will be recorded and further research samples will be taken at those times.

Samples; Blood, urine, stool (in the case of gastroenteritis), nasopharyngeal/throat swab

CONTROLS:

The investigators will collect samples from age-matched control patients will not have had a febrile illness, major trauma or vaccination within the previous three weeks and who are having routine blood sampling for reasons other than investigation of infectious or inflammatory disease.

Control children may include critically ill children without infection or those with healthcare associated infections.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7247
• Est. completion date: December 31, 2021
• Est. primary completion date: January 25, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 17 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Fever
• Infection
• Inflammation

Intervention

Diagnostic Test:
• Validation of biomarker

Locations

Country	Name	City	State
United Kingdom	Imperial College London	London

Sponsors (20)

Lead Sponsor

Collaborator

Imperial College London

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

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

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, Sa — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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

External Links

•   publications and conference proceedings pertaining to PERFORM - BIVA studies