Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05259683 |
| Other study ID # |
278080 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 1, 2022 |
| Est. completion date |
December 31, 2023 |
Study information
| Verified date |
February 2024 |
| Source |
Queen's University, Belfast |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Febrile infants under 3 months of age represent a high risk group for invasive bacterial
infection (IBI) and UTI with approximately 10-20% having bacteremia, meningitis or urinary
tract infection. The assessment of febrile infants is challenging, and current National
Institute for Health and Care Excellence (NICE) guidance advocates a cautious approach with
the majority of infants requiring a septic screen, parenteral broad-spectrum antibiotics, and
admission to hospital. Internationally there is significant variation in the approach to
febrile infants with European and USA guidance advocating a tailored approach based on
clinical features and biomarker testing. None of the available clinical decision aids (CDA)
have been validated in a UK and Irish cohort. The main objectives of the FIDO study are to
report performance accuracy of CDA in a UK (United Kingdom) and Irish population, and
describe the aetiology of SBI in young infants.
The FIDO study is a prospective observational cohort study of infants under 90 days of age
with a measured fever greater than 38 Centrigrade within 24 hours of presentation. The study
will run for approximately 12 months and recruit a minimum of 1000 participants.Symptoms,
clinical features and laboratory results will be recorded on an electronic case report form
(CRF) by the attending clinician.
Description:
Background
Infants below three months of age are at high risk of invasive bacterial infections (IBI) and
urinary tract infections (UTI). Recent studies have reported the combined rate of IBI and UTI
in the range of 10 - 20% , with IBI (bacteremia and meningitis) account for to up to 3% of
the total. Unlike older children infants regularly appear well or have non-specific features
despite having an IBI or UTI, with history and physical examination alone not sufficient to
detect all cases. Furthermore, the clinical differentiation between fever caused by bacteria
and viruses is most challenging in the less than three month age group. The majority of
children still have self-limiting illness in this age group making risk assessment
challenging for clinicians.
The ideal approach to the assessment and management of febrile infants is not clear, as
exemplified by the contrasting approaches advocated by the National Institute for Health and
Care Excellence (NICE). The NICE guideline 51 (NG51) "Sepsis: recognition, diagnosis and
early management" advises that all febrile infants (under 3 months of age) receive parenteral
antibiotics immediately whereas NICE guideline 143 (NG143) "Fever in under 5s: assessment and
initial management" suggests a tailored approach based on clinical assessment and laboratory
testing. The recently proposed British Society for Antimicrobial Chemotherapy (BSAC) guidance
also supports a tailored approach similar to the NICE guideline NG143. The primary aim of
this study is to prospectively validate these CDA.
Objectives Primary Objectives
- Report the aetiology of IBI in febrile infants under three months in the UK and Ireland.
- Describe the clinical and laboratory predictors of IBI in febrile infants under three
months of age.
- Report the performance of tailored CDAs to correctly identify a cohort suitable for
management without parenteral antibiotics.
- Report the performance of tailored CDAs to correctly identify a cohort suitable for
management without lumbar puncture.
Secondary Objectives
- Report a cost analysis for different CDAs.
- Report parents/guardians' and clinicians' views on how best to communicate different
treatment strategies, including the risks and benefits of each.
Study Design A multicentre observational prospective cohort study in the UK and Ireland
conducted via Paediatric Emergency Research in the UK and Ireland (PERUKI).
Study Population All infants 90 days of age and under with a fever of greater than 38
Centigrade during their time in the Emergency Department (ED) or Assessment Unit (AU) or with
a history of fever of greater than 38 Centigrade recorded by anyone via any thermometer type
within the last 24 hours. There are no exclusion criteria, but data will be recorded
regarding gestational age, antenatal complications, underlying health conditions and recent
admissions to hospital.
Setting PERUKI sites across the UK and Ireland.
Screening Eligible participants will be screened by appropriately trained clinical staff,
using the case report form (CRF). The CRF will be used to record anonymised non-personal data
such as baseline demographic data, clinical features and initial examination findings.
Procedures All eligible participants will be enrolled. In all instances routine care will not
be interrupted. Where possible an additional 1ml of blood will be taken and stored for PCT
testing. This blood will be collected during routine phlebotomy. There will be no additional
phlebotomy events beyond those required for routine clinical care. Seven days after discharge
the CRF will be completed by a trained member of the local study team. This will involve
reviewing the medical records and a phone call (maximum of three attempts) to the
parent/guardian to determine if there had been any subsequent unplanned re-attendances to
hospital.
Reference Standards The reference standard is the diagnosis of IBI (meningitis/bacteremia)
and urinary tract infection (excluding contaminants).
Urinary Tract Infection (UTI) will be confirmed by >100,000 CFU/ml of a single organism from
a single clean urine (clean catch, suprapubic aspiration, urethral catheter specimen) or
>100,000 Colony Forming Units (CFU)/ml of the same single organism from two non-clean urines
(pads, bags, cotton wool) and the presence of pyuria (>5 white blood cells per high
powered-field) on laboratory microscopy.
Meningitis will be confirmed by culture or molecular testing of cerebrospinal fluid (CSF).
The reference standard test will be performed by staff blinded to the clinical data and
suspected diagnosis.
Bacteremia will be confirmed by culture or molecular testing of blood. The reference standard
test will be performed by staff blinded to the clinical data and suspected diagnosis.
Contaminants include coagulase negative Staphylococcus, Propionibacterium acnes,
Streptococcus viridans, or Diphtheroides. A list of all suspected contaminants will be
provided at the end of the study.
