Fever Without SourceDIAFEVERNCT03607162
Impact of a PCT(Procalcitonin) Rapid Test -Based Approach on ATB (Antibiotics) Use in Children With Fever Without Source
A study testing DIAFEVER algorithm in people with Fever Without Source, run by Nantes University Hospital at 26 sites in 2 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 6 days to 36 months
- Conditions the study is for
- Fever Without Source
- What is being tested?
- DIAFEVER algorithm
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4,928 participants
- Where
- 26 sitesin 2 countries
- Study dates
- 1 Nov 2018to 3 Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 6 days to 36 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
26 sites in 2 countries.
26 sites in 2 countries
France25 sites
University Hospital
Angers
University Hospital
Bordeaux
University Hospital
Brest
University Hospital
Caen
AP-HP Antoine Béclère
Clamart
University Hospital
Clermont-Ferrand
Hopital Louis Mourier
Colombes
Centre Hospitalier Intercommunal
Créteil
University Hospital
Grenoble
CHD Vendée
La Roche-sur-Yon
Regional University Hospital
Lille
Saint Antoine Saint Vincent Hospital
Lille
Southern Bretagne Hospital
Lorient
Hospices civils de Lyon
Lyon
University Hospital
Montpellier
Regional University Hospital
Nancy
University Hospital
Nice
AP-HP Necker-Enfants Malades
Paris
AP-HP Robert Debré
Paris
Regional University Hospital
Rennes
CHU
Rouen
Saint Brieuc Hospital
Saint-Brieuc
Chu Saint Etienne
Saint-Etienne
University Hospital
Strasbourg
University Hospital
Toulouse
About this study
Official title: 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
Read the 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.
- Conditions
- Fever Without Source
- Being tested
- DIAFEVER algorithm
- Keywords
- Bacteriemia, meningitis, Urinary tract infection, antibiotic treatment
- Medical subject headings
- Meningitis, Urinary Tract Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DIAFEVER algorithmDiagnostic test
PCT rapid test-based predictive algorithm
| Study group | Role | What they receive |
|---|---|---|
| Usual care | No intervention | Local usual management of FWS (pragmatic approach) |
| DIAFEVER algorithm | Experimental | New DIAFEVER sequential algorithm PCT rapid test-based will be applied Receives: Diagnostic Test: DIAFEVER algorithm |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in antibiotics exposure
Related to the superiority objective : change in antibiotics exposure based on the proportion of children who received ABT
Measured: at day 15 after the first ED consultation
Secondary outcomes (8)
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
Measured: 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
Measured: At inclusion visit
Impact of the DIAFEVER prediction rule on median length of stay in the ED
Measured: at day 15 after the first ED consultation
Impact of the DIAFEVER prediction rule on the proportion of children with laboratory tests prescription
Measured: at day 15 after the first ED consultation
Impact of the DIAFEVER prediction rule on hospitalization rates
Measured: 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)
Measured: 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
Measured: 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
Measured: at day 15 after the first ED consultation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2018
- Study start1 Nov 2018
- Primary completion3 Dec 2021
- Study completion3 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Fever Without SourceStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- 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 blind
- Who is masked
- Participant
- Enrolment
- 4,928 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03607162
- Sponsor's protocol ID
- RC18_0042
- Acronym
- DIAFEVER
- Status last verified
- Dec 2021
- First submitted
- 10 Jul 2018
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Malorey D, Tavernier E, Drouard A, Vrignaud B, Bailhache M, Guyon G, Titomanlio L, Brehin C, Abalea L, Gervaix A, Basmaci R, Dubos F, Tran A, Desgranges M, Launay E, Gras-Leguen C; Diafever Study Group. Point-of-care decision rule for antibiotic prescriptions in young children with fever without source: an open cluster randomised trial. Arch Dis Child. 2026 Mar 17:archdischild-2025-329438. doi: 10.1136/archdischild-2025-329438. Online ahead of print.
PubMed 41407517Hubert 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.
PubMed 32792425
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of a New Sequential Approach on Antimicrobial Use in Young Children With Fever Without Source in Emergency Department
- ClinicalTrials.gov ID
- NCT03607162
- Acronym / sponsor ID
- DIAFEVER / RC18_0042
- Conditions
- Fever Without Source
- Keywords
- Bacteriemia, meningitis, Urinary tract infection, antibiotic treatment
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4,928 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Study start
- 1 Nov 2018 (actual)
- Primary completion
- 3 Dec 2021 (actual)
- Study completion
- 3 Dec 2021 (actual)
- First posted
- 31 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Usual care | No intervention | –Local usual management of FWS (pragmatic approach) |
| DIAFEVER algorithm | Experimental | Diagnostic Test: DIAFEVER algorithmNew DIAFEVER sequential algorithm PCT rapid test-based will be applied |
Who may qualify
- Ages
- 6 days to 36 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
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 |
|---|---|---|
| DIAFEVER algorithmPCT rapid test-based predictive algorithm | Diagnostic test | DIAFEVER algorithm |
Primary outcome
Change in antibiotics exposure
Time frame: at day 15 after the first ED consultation
Related to the superiority objective : change in antibiotics exposure based on the proportion of children who received ABT
8 secondary outcomes
Description of the current epidemiology of FWS among children < 36 months old admitted in an ED
Time frame: At inclusion visit
Diagnostic value of the DIAFEVER prediction rule for SBI and IBI diagnosis
Time frame: At inclusion visit
Impact of the DIAFEVER prediction rule on median length of stay in the ED
Time frame: at day 15 after the first ED consultation
Impact of the DIAFEVER prediction rule on the proportion of children with laboratory tests prescription
Time frame: at day 15 after the first ED consultation
Impact of the DIAFEVER prediction rule on hospitalization rates
Time frame: 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)
Time frame: at day 15 after the first ED consultation
theoretically vaccine-preventable SBI
Time frame: at day 15 after the first ED consultation
morbidity and mortality
Time frame: at day 15 after the first ED consultation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
- Results publication: PubMed 41407517Malorey D, Tavernier E, Drouard A, Vrignaud B, Bailhache M, Guyon G, Titomanlio L, Brehin C, Abalea L, Gervaix A, Basmaci R, Dubos F, Tran A, Desgranges M, Launay E, Gras-Leguen C; Diafever Study Group. Point-of-care decision rule for antibiotic prescriptions in young children with fever without source: an open cluster randomised trial. Arch Dis Child. 2026 Mar 17:archdischild-2025-329438. doi: 10.1136/archdischild-2025-329438. Online ahead of print.
- Derived from this study: PubMed 32792425Hubert 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.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
26 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing DIAFEVER algorithm in people with Fever Without Source, run by Nantes University Hospital at 26 sites in 2 countries.
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 5 inclusion and 7 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 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in France, Switzerland. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in antibiotics exposure (time frame: at day 15 after the first ED consultation). 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 NCT03607162, 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 14 Sep 2026.