Personalised Risk Assessment in Febrile Illness to Optimise Real-life Management Across the European Union (PERFORM)
Study Details
Study Description
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.
There are two parts to recruitment in this study; the first is to assess the management and outcome of febrile children who seek medical treatment in hospital (MOFICHE study). The data will be used to model management strategies for febrile children and enable a cost-effectiveness analysis.
Secondly 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed 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.
There are two components to the study design;
- MOFICHE study:
Observe the management and outcome of children presenting to Emergency Departments (ED) with fever across Europe (MOFICHE study.
STUDY SIZE: at least 50,000 febrile children
PROCEDURES:
Data of all febrile children will be flagged at triage and a standardised dataset will be collected.
- Biomarker Validation (BIVA studies):
Validate biomarkers using prospectively recruited patients and patient samples (Biomarker Validation studies (BIVA))
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).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| MOFICHE This is an observational study assessing the management and outcome of children presenting to Emergency Departments (ED) with fever across Europe. This study will use large departmental datasets to collect information on at least 50,000 febrile episodes . This study will use large-scale, pseudo-anonymized departmental data, and will not involve consented patient recruitment; nor will it use patient samples. Data included in MOFICHE will be based on that collected as part of routine clinical care. Antibiotic prescription, hospitalisation and number/type of investigations, re-attendance at ED within 5 days of the first hospital presentation will be recorded. |
Other: Antibiotic prescription
Other: re-attendance at ED
Other: Hospitalisation
|
| BIVA studies A minimum of 3,000 children will be recruited to the BIVA-ED 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
|
Outcome Measures
Primary Outcome Measures
- MOFICHE study standardised dataset will be collected [throughout the study over one year]
Duration of antimicrobial treatment
- BIVA studies assessment of the ability of biomarker tests [throughout the study over 3 years]
Assessment of the ability of biomarker tests to distinguish between bacterial and viral disease in febrile children
Secondary Outcome Measures
- MOFICHE study accessed the records [throughout the study one year]
Number of prescriptions of broad spectrum antibiotics versus the number of prescription of narrow spectrum antibiotics (dose in 24 hours)
- BIVA study assessment of the ability of biomarker tests to predict disease severity [throughout the study 3 years]
Assessment of the ability of biomarker tests to predict disease severity
Eligibility Criteria
Criteria
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.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Imperial College London | London | United Kingdom | W2 1PG |
Sponsors and Collaborators
- Imperial College London
- Servizo Galego de Saúde
- London School of Hygiene and Tropical Medicine
- University of Liverpool
- University of Newcastle Upon-Tyne
- Erasmus Medical Center
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- National and Kapodistrian University of Athens
- Stichting Katholieke Universiteit
- University of Graz
- University of Ljubljana
- Riga Stradiņs University
- Medical Research Council Unit, The Gambia
- Ludwig-Maximilians - University of Munich
- University of Bern
- University of Oxford
- University Hospital, Paris
Investigators
- Study Chair: Michael Levin, Imperial College London
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- REC ref: 16/LO/1684