Impact of a PCT(Procalcitonin) Rapid Test -Based Approach on ATB (Antibiotics) Use in Children With Fever Without Source

Study Overview
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Brief Summary
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Because a newly available point-of-care test may have real interest especially for children in the Emergency Department (ED) setting, by limiting painful and stressful venipunctures and decreasing the length of stay in the ED, the investigators hypothesize that integrating this new capillary Procalcitonin (PCT) rapid test in the DIAFEVER CPR (Clinical Prediction Rules) could represent a highly valuable diagnostic tool to identify a group with low Invasive Bacterial Infection (IBI) risk and could limit unnecessary exams and antibiotic prescriptions. The aim of this present study is to demonstrate the impact of this new PCT rapid-test-based CPR on antibiotic prescription rate in young children with Fever Without Source (FWS) presenting to the ED and on morbidity and mortality

Detailed Description
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This prospective multicentric randomized study will include 5000 febrile children aged six days to three years, diagnosed with fever without source, in 26 participating French and Swiss emergency departments, during a 36-month period. During one period, all children will receive usual care. In a second period, the DIAFEVER algorithm will be applied in half of the clusters, and in the remaining clusters, children will still receive usual care. Then in the last period of one year, all centers will apply the new PCT-based algorithm. At day 15 after the first consultation, data concerning death, intensive care unit admission, disease-specific complications, diagnosis of bacterial infections and proportion of antibiotic treatments will be assessed by questioning parents by use of an online electronic case report form or a phone call. The endpoints will be compared between the two groups by using a mixed logistic regression model adjusted on clustering of participants within centers and period within centers. To perform complementary studies, a biocollection will be proposed to parents when blood tests will be indicated.

Official Title
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Impact of a New Sequential Approach on Antimicrobial Use in Young Children With Fever Without Source in Emergency Department

Conditions
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Fever Without Source

Intervention / Treatment
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* Diagnostic Test: DIAFEVER algorithm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Febrile children aged 6 days to <36 months old presenting to an ED at their initial visit with an acute illness for a maximum of 8 days and diagnosed with a FWS defined as body temperature (measured at home or the ED) > 38°C and a physical examination by a physician without source Oral non-opposition will be requested from one of the parents or caregivers of the patient. No current antibiotic treatment or within the 48 hours before the ED presentation. Parental affiliation with an appropriate health insurance system Parents speaking French Exclusion Criteria: A clear source of fever identified after a careful inspection of medical history and a physical examination No fever on consultation or previously subjectively assessed by parents without use of a thermometer Refusal of the parents to participate Child ≥ 36 months or < 6 days old (ie, early-onset neonatal infection) Ongoing ABT treatment or within the 48 hours before ED presentation Children with FWS who revisited the ED after their initial visit Participation with another interventional study involving human subjects or being in the exclusion period at the end of a previous study involving human subjects

Ages Eligible for Study
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Minimum Age: 6 Days
Maximum Age: 36 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is an open cluster randomized clinical trial with random and sequential crossover of clusters from control to intervention until all clusters are exposed. Clusters are defined as EDs. 2 periods will be considered, one when all children will receive usual care, whatever the cluster, and a second one when, in half of the clusters, the DIAFEVER algorithm will be applied, and in the remaining clusters, children will still receive usual care.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Usual care<br>Local usual management of FWS (pragmatic approach) | |
| Experimental: DIAFEVER algorithm<br>New DIAFEVER sequential algorithm PCT rapid test-based will be applied | Diagnostic Test: DIAFEVER algorithm<br>* PCT rapid test-based predictive algorithm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in antibiotics exposure | Related to the superiority objective : change in antibiotics exposure based on the proportion of children who received ABT | at day 15 after the first ED consultation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of the current epidemiology of FWS among children < 36 months old admitted in an ED | The incidence of FWS among children admitted in EDs, the incidence of Severe Bacterial Infection (SBI) and IBI among the children admitted in the ED with FWS | At inclusion visit | 
| Diagnostic value of the DIAFEVER prediction rule for SBI and IBI diagnosis | Assessment of sensitivity, specificity, predictive values, Likelihood Ratio, of the DIAFEVER prediction rule (combining high- and intermediate-risk versus low-risk populations) considering the SBI/IBI diagnosis as the gold standard | At inclusion visit | 
| Impact of the DIAFEVER prediction rule on median length of stay in the ED |  | at day 15 after the first ED consultation | 
| Impact of the DIAFEVER prediction rule on the proportion of children with laboratory tests prescription |  | at day 15 after the first ED consultation | 
| Impact of the DIAFEVER prediction rule on hospitalization rates |  | at day 15 after the first ED consultation | 
| vaccine coverage of children consulting for FWS evaluated by the vaccination coverage rate (among children with FWS) |  | at day 15 after the first ED consultation | 
| theoretically vaccine-preventable SBI | theoretically vaccine-preventable SBI is defined as an infection with an identified serotype included in the national vaccine schedule and occurring in a child with untimely vaccination | at day 15 after the first ED consultation | 
| morbidity and mortality | Morbidity and mortality based on a binary composite outcome considering occurrence or not during the 15 days after discharge from the ED of one of the following events: death intensive care unit admission for any reason disease-specific complications (ie, cerebral damage with neurologic impairment, deathless, blindness amputation, cutaneous necrosis requiring surgery, definitive renal failure etc.) diagnosis of Invasive Bacterial Infection or Serious Bacterial Infection | at day 15 after the first ED consultation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bacteriemia, meningitis, Urinary tract infection, antibiotic treatment