FeverPERFORMNCT03502993
Personalised Risk Assessment in Febrile Illness to Optimise Real-life Management Across the European Union (PERFORM)
An observational study of Fever and Infection, run by Imperial College London at 1 site in United Kingdom.
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… Read more about this study
- Who is it for?
- Ages Up to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Fever, Infection, Inflammation
- What is being tested?
- Validation of biomarker
- How many people
- 7,247 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 2 Jun 2016to 31 Dec 2021
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 17 years
- All sexes
- Healthy volunteers accepted
- Child
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,
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
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.
- Conditions
- Fever, Infection, Inflammation
- Being tested
- Validation of biomarker
- Keywords
- children
- Medical subject headings
- Fever, Infections, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Validation of biomarkerDiagnostic test
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Diagnostic Test: Validation of biomarker |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Clinically-assigned Retrospective Phenotype
Clinically-assigned retrospective phenotype, according to the cause of illness
Measured: Participants were monitored for outcome throughout their stay in hospital, and received follow-up review at 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2018
- Study start2 Jun 2016
- Primary completion25 Jan 2021
- Study completion31 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for FeverStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 7,247 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- 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 Stradins University, Medical Research Council Unit, The Gambia, Ludwig-Maximilians - University of Munich, University of Bern, University of Oxford, University Hospital, Paris, University of Santiago de Compostela, Servicio Gallego de Salud, BioMérieux, Micropathology Ltd, University of Warwick
- Responsible party
- Sponsor
- Investigators
- Michael Levin, Study chair, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03502993
- Sponsor's protocol ID
- REC ref: 16/LO/1684
- Other IDs
- BIVA studies
- Acronym
- PERFORM
- Status last verified
- Oct 2023
- First submitted
- 27 Mar 2018
- Last updated
- 13 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37597512Hartman 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.
PubMed 34036552
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Personalised Risk Assessment in Febrile Illness to Optimise Real-life Management Across the European Union (PERFORM)
- ClinicalTrials.gov ID
- NCT03502993
- Acronym / sponsor ID
- PERFORM / REC ref: 16/LO/1684
- Conditions
- Fever, Infection, Inflammation
- Keywords
- children
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 7,247 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- 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 Stradins University, Medical Research Council Unit, The Gambia, Ludwig-Maximilians - University of Munich, University of Bern, University of Oxford, University Hospital, Paris, University of Santiago de Compostela, Servicio Gallego de Salud, BioMérieux, Micropathology Ltd, University of Warwick
- Study start
- 2 Jun 2016 (actual)
- Primary completion
- 25 Jan 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 19 Apr 2018 (actual)
- Results
- Posted 13 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
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
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BIVA studies - children with fever and/or suspected infection | – | Diagnostic Test: Validation of biomarkerA 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. |
| BIVA studies - control children without fever or suspicion of infection | – | Diagnostic Test: Validation of biomarkerAfebrile 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. |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- 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,
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Validation of biomarker | Diagnostic test | BIVA studies - children with fever and/or suspected infection, BIVA studies - control children without fever or suspicion of infection |
Primary outcome
Number of Participants With Clinically-assigned Retrospective Phenotype
Time frame: Participants were monitored for outcome throughout their stay in hospital, and received follow-up review at 10 days
Clinically-assigned retrospective phenotype, according to the cause of illness
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 37597512Habgood-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.
- Derived from this study: PubMed 34036552Hartman 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.
- publications and conference proceedings pertaining to PERFORM - BIVA studiesLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Levin study chair
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Fever and Infection, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Clinically-assigned Retrospective Phenotype (time frame: Participants were monitored for outcome throughout their stay in hospital, and received follow-up review at 10 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03502993, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2023.