Early-onset Neonatal InfectionDIACORDNCT02590198
Diagnostic Performance Comparison Between Procalcitonin-based vs. ANAES-based Guidelines
An observational study of Early-onset Neonatal Infection, run by Nantes University Hospital at 14 sites in France.
Trial summary
Neonatal bacterial infection remains a serious pathology in industrialized countries despite the use of prophylaxis measures for group B streptococcus (GBS) (peri-partum antibiotic in women with GBS colonization), which was implemented in the United States in 1996 and in France in 2001 and has led to a dramatic… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Early-onset Neonatal Infection
- What is being tested?
- ANAES algorithm and PCT algorithm
- How many people
- 9,201 participants
- Where
- 14 sitesFrance
- Study dates
- 3 May 2016to 22 Jan 2017
- Phase
- Observational
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Children included in the DIACORD study will be born at > 36 weeks gestation in one of the 15 participating maternity or neonatology units and suspected of EOSI according to the ANAES recommendations (clinical suspicion of chorioamnionitis; intrapartum maternal fever > 38°C, infected twin, spontaneous premature delivery at < 37 gestational weeks, prolonged rupture of membrane for > 12 hours, maternal colonization with group B Streptococcus without full prophylactic antibiotic treatment, or signs of fetal asphyxia).
Who may be able to join
- All children born at > 36 weeks gestation in one of the 15 participating maternity or neonatology units and suspected having EONI according to the ANAES recommendations (clinical suspicion of chorioamnionitis, intrapartum maternal fever > 38°C, infected twin, spontaneous premature delivery at < 37 gestational weeks, prolonged rupture of membrane for > 12 hours, maternal group B Streptococcus colonization without full prophylactic antibiotic treatment, or signs of fetal asphyxia) will be included in the study.
- Oral Consent (Non Opposition).
Who cannot join
- Newborns will be considered ineligible if:
- Parental non opposition is not obtained, if the parents do not speak French, present severe dementia and/or cannot be reached on day 6.
- Nosocomial neonatal infection, severe congenital malformation or obstetrically explained neonatal asphyxia are diagnosed.
- Secondary parental opposition.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
France14 sites
Angers University Hospital
Angers, 49933
Bordeaux University Hospital
Bordeaux, 33404
Brest University Hospital
Brest, 29609
Créteil Intercommunal Center
Créteil, 94010
Lorient Hospital
Lorient, 56322
Private clinic - Polyclinique de l'Atlantique
Nantes, 44819
La Pitié Salpétrière Hospital (AP-HP)
Paris, 75010
Robert Debré Hospital (AP-HP)
Paris, 75010
Trousseau Hospital (AP-HP)
Paris, 75010
Saint Joseph Hospital
Paris, 75014
Poissy-Saint germain Hospital
Poissy, 78300
Poitiers University Hospital
Poitiers, 86021
Rennes University Hospital
Rennes, 35033
Tours University Hospital
Tours, 37044
About this study
Official title: Diagnostic Performance Comparison Between Procalcitonin-based vs. ANAES-based Guidelines; Impact on Antibiotic Use in Newborns With Suspected Early-onset Neonatal Infection (EONI)
Neonatal bacterial infection remains a serious pathology in industrialized countries despite the use of prophylaxis measures for group B streptococcus (GBS) (peri-partum antibiotic in women with GBS colonization), which was implemented in the United States in 1996 and in France in 2001 and has led to a dramatic decrease in the incidence of neonatal bacterial infections. However, early onset neonatal infection (EONI), which is defined as an infection occurring during the first 6 days after birth (as opposed to late onset neonatal infections (LONI) occurring between days 7-89), is still one of the leading causes of neonatal morbidity and mortality. Physicians consider EONI a significant diagnostic and therapeutic emergency due to the potential for sudden onset and rapid evolution of sepsis in newborns with immature immune systems. Currently, in France, detection of EONI is based on national consensus guidelines published in 2002 (ANAES recommendations). There are broad indications to provide empirical antibiotic treatment pending diagnostic confirmation through different complementary exams. To ensure that every infected newborn is diagnosed, biological assessments are often repeated and result in the use of invasive and painful procedures, anemia and financial concerns. Moreover, in cases of abnormal biological results, many newborns are subjected to intravenous (IV) antibiotic treatments requiring hospitalization and separation from their mother. However recent studies have shown that antibiotics can have a potentially deleterious effect on the neonatal digestive microbiota and result in the appearance of antibiotic-resistant bacteria, with possible long-term consequences on the health of the child.
Procalcitonin (PCT) is a calcitonin prohormone secreted from the parenchymal tissues. This marker of inflammation has been shown to be a valuable diagnostic marker for bacterial infection in adults and in children. It also seems to be a reliable marker for neonatal bacterial infection, which would make it useful in the detection of EONI. Because physiological levels of PCT vary during the first days of life, possibly due to postnatal intestinal bacterial colonization, levels of this marker are difficult to interpret in the early neonatal period. However, in a study of 2151 newborns with suspected EONI, Nicolas Joram et al. found that PCT obtained from the umbilical blood cord, prior to newborn intestinal colonization, bypasses this postnatal physiological peak of PCT and effectively constitutes a discriminant marker to distinguish between infected and healthy infants using a cutoff value of 0.6 ng/ml.
Read more
Subsequent to this pilot study, several studies on PCT in umbilical blood cord confirmed its good diagnostic performance for EONI, particularly when included in a diagnostic algorithm. This marker could contribute to a better estimation of EONI risk in order to limit the use of unnecessary complementary exams and prescription of antibiotics and their associated short- and long-term side effects in healthy newborns.
Therefore, in this study, the investigators propose to test the diagnostic value of a PCT-based algorithm in newborns suspected of having EONI. The investigators hypothesize that this algorithm is as efficient as those currently used (ANAES), but will limit coinciding biological exams and exposure to antibiotics during the neonatal period.
- Conditions
- Early-onset Neonatal Infection
- Being tested
- ANAES algorithm, PCT algorithm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ANAES algorithmOther
care as recommended by ANAES, with ANAES algorithm
PCT algorithmOther
care based on PCT algorithm
| Study group | Role | What they receive |
|---|---|---|
| ANAES algorithm | Each center will start the study by applying the usual ANAES algorithm. The date of implementation of the new algorithm based on PCT will be determined randomly. Therefore, within each center, there will be an initial period in which the standard algorithm is applied and a second one during which the PCT-based algorithm is applied Receives: Other: ANAES algorithm; Other: PCT algorithm | |
| PCT algorithm | Each center will start the study by applying the usual ANAES algorithm. The date of implementation of the new algorithm based on PCT will be determined randomly. Therefore, within each center, there will be an initial period in which the standard algorithm is applied and a second one during which the PCT-based algorithm is applied Receives: Other: ANAES algorithm; Other: PCT algorithm |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary outcome is a composite outcome including: death from any cause, intensive care unit admission for any reason, disease-specific complications, diagnosis of EONI after maternity discharge, need for antibiotics with hospital readmission
The primary noninferiority endpoint is a composite of overall adverse outcomes induced by EONI occuring within 6 days following birth. It includes death, Neonatal Intensive care Unit (NICU) admission, or hospital readmission. The investigators chose this primary endpoint because the French definition of EONI diagnostic is subjective, specifically in case of possible EONI in case of gastric fluid positivity, and is finally rarely objectivated. Moreover, the new PCT-based algorithm do not require any gastric fluid analysis and modify the usual French definition of possible EONI, impossible to use in this context. Focusing on serious adverse event outcomes seems a very pragmatic and efficient methodologic strategy.
Measured: 6 days after birth
Secondary outcomes (8)
death
components of the primary outcome (death/NICU/rehospitalisation + antibiotics) will be considered independently, as is advised for a composite outcome.
Measured: Day 6 and Day 90
NICU admission
components of the primary outcome (death/NICU/rehospitalisation + antibiotics) will be considered independently, as is advised for a composite outcome.
Measured: Day 6 and Day 90
rehospitalisation in connection with antibiotic treatment
components of the primary outcome (death/NICU/rehospitalisation + antibiotics) will be considered independently, as is advised for a composite outcome.
Measured: Day 6 and Day 90
Inter-period frequency comparison of secondary adverse effect (SAE) and adverse effect (AE) related to antibiotics.
Measured: Day 6 and Day 90
Number of blood samples induced by the 2 algorithms
EONI diagnostic exams frequency for EONI induced by the 2 algorithms (number of blood samples)
Measured: Day 6 and Day 90
Number of newborns investigated by the 2 algorithms
EONI diagnostic exams frequency for EONI induced by the 2 algorithms ( number of newborns investigated).
Measured: Day 6 and Day 90
Inter-period cumulated hospital stay length (including maternity stay)
Measured: Day 90
clinical and biological description of EONI and LONI
Description of EONI and LONI bacteriological epidemiology (No recent data in France and Europe): frequency, typology...
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2015 (estimated)
- Study start3 May 2016
- Primary completion22 Jan 2017
- Study completion22 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Early-onset Neonatal InfectionStudies 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 9,201 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Tours, University Hospital, Brest, Rennes University Hospital, Poitiers University Hospital, University Hospital, Angers, University Hospital, Bordeaux, Centre Hospitalier de Bretagne Sud, University Hospital, Paris, Créteil Hospital, Nantes Polyclinic
- Responsible party
- Sponsor
- Investigators
- GRAS-LEGUEN Christele, PU-PH, Principal investigator, Nantes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02590198
- Sponsor's protocol ID
- RC15_0063
- Acronym
- DIACORD
- Status last verified
- Sep 2019
- First submitted
- 12 Oct 2015
- Last updated
- 20 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diagnostic Performance Comparison Between Procalcitonin-based vs. ANAES-based Guidelines; Impact on Antibiotic Use in Newborns With Suspected Early-onset Neonatal Infection (EONI)
- ClinicalTrials.gov ID
- NCT02590198
- Acronym / sponsor ID
- DIACORD / RC15_0063
- Conditions
- Early-onset Neonatal Infection
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 9,201 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Collaborators
- University Hospital, Tours, University Hospital, Brest, Rennes University Hospital, Poitiers University Hospital, University Hospital, Angers, University Hospital, Bordeaux, Centre Hospitalier de Bretagne Sud, University Hospital, Paris, Créteil Hospital, Nantes Polyclinic
- Study start
- 3 May 2016 (actual)
- Primary completion
- 22 Jan 2017 (actual)
- Study completion
- 22 Jan 2017 (actual)
- First posted
- 28 Oct 2015 (estimated)
- 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.
Neonatal bacterial infection remains a serious pathology in industrialized countries despite the use of prophylaxis measures for group B streptococcus (GBS) (peri-partum antibiotic in women with GBS colonization), which was implemented in the United States in 1996 and in France in 2001 and has led to a dramatic decrease in the incidence of neonatal bacterial infections. However, early onset neonatal infection (EONI), which is defined as an infection occurring during the first 6 days after birth (as opposed to late onset neonatal infections (LONI) occurring between days 7-89), is still one of the leading causes of neonatal morbidity and mortality. Physicians consider EONI a significant diagnostic and therapeutic emergency due to the potential for sudden onset and rapid evolution of sepsis in newborns with immature immune systems. Currently, in France, detection of EONI is based on national consensus guidelines published in 2002 (ANAES recommendations). There are broad indications to provide empirical antibiotic treatment pending diagnostic confirmation through different complementary exams. To ensure that every infected newborn is diagnosed, biological assessments are often repeated and result in the use of invasive and painful procedures, anemia and financial concerns. Moreover, in cases of abnormal biological results, many newborns are subjected to intravenous (IV) antibiotic treatments requiring hospitalization and separation from their mother. However recent studies have shown that antibiotics can have a potentially deleterious effect on the neonatal digestive microbiota and result in the appearance of antibiotic-resistant bacteria, with possible long-term consequences on the health of the child.
Procalcitonin (PCT) is a calcitonin prohormone secreted from the parenchymal tissues. This marker of inflammation has been shown to be a valuable diagnostic marker for bacterial infection in adults and in children. It also seems to be a reliable marker for neonatal bacterial infection, which would make it useful in the detection of EONI. Because physiological levels of PCT vary during the first days of life, possibly due to postnatal intestinal bacterial colonization, levels of this marker are difficult to interpret in the early neonatal period. However, in a study of 2151 newborns with suspected EONI, Nicolas Joram et al. found that PCT obtained from the umbilical blood cord, prior to newborn intestinal colonization, bypasses this postnatal physiological peak of PCT and effectively constitutes a discriminant marker to distinguish between infected and healthy infants using a cutoff value of 0.6 ng/ml.
Subsequent to this pilot study, several studies on PCT in umbilical blood cord confirmed its good diagnostic performance for EONI, particularly when included in a diagnostic algorithm. This marker could contribute to a better estimation of EONI risk in order to limit the use of unnecessary complementary exams and prescription of antibiotics and their associated short- and long-term side effects in healthy newborns.
Therefore, in this study, the investigators propose to test the diagnostic value of a PCT-based algorithm in newborns suspected of having EONI. The investigators hypothesize that this algorithm is as efficient as those currently used (ANAES), but will limit coinciding biological exams and exposure to antibiotics during the neonatal period.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ANAES algorithm | – | Other: ANAES algorithm, Other: PCT algorithmEach center will start the study by applying the usual ANAES algorithm. The date of implementation of the new algorithm based on PCT will be determined randomly. Therefore, within each center, there will be an initial period in which the standard algorithm is applied and a second one during which the PCT-based algorithm is applied |
| PCT algorithm | – | Other: ANAES algorithm, Other: PCT algorithmEach center will start the study by applying the usual ANAES algorithm. The date of implementation of the new algorithm based on PCT will be determined randomly. Therefore, within each center, there will be an initial period in which the standard algorithm is applied and a second one during which the PCT-based algorithm is applied |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Children included in the DIACORD study will be born at > 36 weeks gestation in one of the 15 participating maternity or neonatology units and suspected of EOSI according to the ANAES recommendations (clinical suspicion of chorioamnionitis; intrapartum maternal fever > 38°C, infected twin, spontaneous premature delivery at < 37 gestational weeks, prolonged rupture of membrane for > 12 hours, maternal colonization with group B Streptococcus without full prophylactic antibiotic treatment, or signs of fetal asphyxia).
Key inclusion criteria (2 listed)
- All children born at > 36 weeks gestation in one of the 15 participating maternity or neonatology units and suspected having EONI according to the ANAES recommendations (clinical suspicion of chorioamnionitis, intrapartum maternal fever > 38°C, infected twin, spontaneous premature delivery at < 37 gestational weeks, prolonged rupture of membrane for > 12 hours, maternal group B Streptococcus colonization without full prophylactic antibiotic treatment, or signs of fetal asphyxia) will be included in the study.
- Oral Consent (Non Opposition).
Key exclusion criteria (4 listed)
- Newborns will be considered ineligible if:
- Parental non opposition is not obtained, if the parents do not speak French, present severe dementia and/or cannot be reached on day 6.
- Nosocomial neonatal infection, severe congenital malformation or obstetrically explained neonatal asphyxia are diagnosed.
- Secondary parental opposition.
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 |
|---|---|---|
| ANAES algorithmcare as recommended by ANAES, with ANAES algorithm | Other | ANAES algorithm, PCT algorithm |
| PCT algorithmcare based on PCT algorithm | Other | ANAES algorithm, PCT algorithm |
Primary outcome
Primary outcome is a composite outcome including: death from any cause, intensive care unit admission for any reason, disease-specific complications, diagnosis of EONI after maternity discharge, need for antibiotics with hospital readmission
Time frame: 6 days after birth
The primary noninferiority endpoint is a composite of overall adverse outcomes induced by EONI occuring within 6 days following birth. It includes death, Neonatal Intensive care Unit (NICU) admission, or hospital readmission. The investigators chose this primary endpoint because the French definition of EONI diagnostic is subjective, specifically in case of possible EONI in case of gastric fluid positivity, and is finally rarely objectivated. Moreover, the new PCT-based algorithm do not require any gastric fluid analysis and modify the usual French definition of possible EONI, impossible to use in this context. Focusing on serious adverse event outcomes seems a very pragmatic and efficient methodologic strategy.
8 secondary outcomes
death
Time frame: Day 6 and Day 90
NICU admission
Time frame: Day 6 and Day 90
rehospitalisation in connection with antibiotic treatment
Time frame: Day 6 and Day 90
Inter-period frequency comparison of secondary adverse effect (SAE) and adverse effect (AE) related to antibiotics.
Time frame: Day 6 and Day 90
Number of blood samples induced by the 2 algorithms
Time frame: Day 6 and Day 90
Number of newborns investigated by the 2 algorithms
Time frame: Day 6 and Day 90
Inter-period cumulated hospital stay length (including maternity stay)
Time frame: Day 90
clinical and biological description of EONI and LONI
Time frame: 12 months
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 20 Sep 2019.
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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.
GRAS-LEGUEN Christele, PU-PH principal investigator
Nantes University Hospital
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Early-onset Neonatal Infection, run by Nantes University Hospital at 14 sites in France.
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 2 inclusion and 4 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 20 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in France. 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?
Primary outcome is a composite outcome including: death from any cause, intensive care unit admission for any reason, disease-specific complications, diagnosis of EONI after maternity discharge, need for antibiotics with hospital readmission (time frame: 6 days after birth). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Sep 2019.