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

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

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

Study Overview

• Status: Completed
• Conditions: Fever Without Source
• Intervention / Treatment: Diagnostic test: DIAFEVER algorithm

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 4928
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France
    • University Hospital
  • Bordeaux, France
    • University Hospital
  • Brest, France
    • University Hospital
  • Caen, France
    • University Hospital
  • Clamart, France
    • AP-HP Antoine Béclère
  • Clermont-Ferrand, France
    • University Hospital
  • Colombes, France
    • Hopital Louis Mourier
  • Créteil, France
    • Centre Hospitalier Intercommunal
  • Grenoble, France
    • University Hospital
  • La Roche-sur-Yon, France
    • CHD Vendee
  • Lille, France
    • Regional University Hospital
  • Lille, France
    • Saint Antoine Saint Vincent Hospital
  • Lorient, France
    • Southern Bretagne Hospital
  • Lyon, France
    • Hospices Civils de Lyon
  • Montpellier, France
    • University Hospital
  • Nancy, France
    • Regional University Hospital
  • Nice, France
    • University Hospital
  • Paris, France
    • AP-HP Necker-Enfants malades
  • Paris, France
    • AP-HP Robert Debré
  • Rennes, France
    • Regional University Hospital
  • Rouen, France
    • CHU
  • Saint-Brieuc, France
    • Saint Brieuc Hospital
  • Saint-Étienne, France
    • CHU Saint Etienne
  • Strasbourg, France
    • University Hospital
  • Toulouse, France
    • University Hospital
• Switzerland
  • Geneva, Switzerland
    • Hôpital des Enfants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Publications and helpful links

General Publications

• Hubert G, Launay E, Feildel Fournial C, Chauvire-Drouard A, Lorton F, Tavernier E, Giraudeau B, Gras Le Guen C. Assessment of the impact of a new sequential approach to antimicrobial use in young febrile children in the emergency department (DIAFEVERCHILD): a French prospective multicentric controlled, open, cluster-randomised, parallel-group study protocol. BMJ Open. 2020 Aug 13;10(8):e034828. doi: 10.1136/bmjopen-2019-034828.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): December 3, 2021
• Study Completion (Actual): December 3, 2021

Study Registration Dates

• First Submitted: July 10, 2018
• First Submitted That Met QC Criteria: July 30, 2018
• First Posted (Actual): July 31, 2018

Study Record Updates

• Last Update Posted (Actual): December 21, 2021
• Last Update Submitted That Met QC Criteria: December 20, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: meningitis; Urinary tract infection; antibiotic treatment; Bacteriemia
• Additional Relevant MeSH Terms: Body Temperature Changes; Fever
• Other Study ID Numbers: RC18_0042

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No