Diagnostic Performance Comparison Between Procalcitonin-based vs. ANAES-based Guidelines

NCT02590198 | Completed

• 1 other identifier: RC15_0063
• Study Type: observational
• Target: 9,201
• Locations: 1 country
• Sites: 14

Brief 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 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.

Conditions

Early-onset Neonatal Infection

Outcome Measures

Primary Outcomes (1)

• 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.

  6 days after birth

Secondary Outcomes (8)

• death

  Day 6 and Day 90

• NICU admission

  Day 6 and Day 90

• rehospitalisation in connection with antibiotic treatment

  Day 6 and Day 90

• Inter-period frequency comparison of secondary adverse effect (SAE) and adverse effect (AE) related to antibiotics.

  Day 6 and Day 90

• Number of blood samples induced by the 2 algorithms

  Day 6 and Day 90

Study Arms (2)

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

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

Other: ANAES algorithm; Other: PCT algorithm

Interventions

ANAES algorithm OTHER

care as recommended by ANAES, with ANAES algorithm

ANAES algorithm; PCT algorithm

PCT algorithm OTHER

care based on PCT algorithm

ANAES algorithm; PCT algorithm

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

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).

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nantes University Hospital: lead
• University Hospital, Tours: collaborator
• University Hospital, Brest: collaborator
• Rennes University Hospital: collaborator
• Poitiers University Hospital: collaborator
• University Hospital, Angers: collaborator
• University Hospital, Bordeaux: collaborator
• Centre Hospitalier de Bretagne Sud: collaborator
• University Hospital, Paris: collaborator
• Créteil Hospital: collaborator
• Nantes Polyclinic: collaborator

Study Sites (14)

Angers University Hospital

Angers, 49933, France

Location

Bordeaux University Hospital

Bordeaux, 33404, France

Location

Brest University Hospital

Brest, 29609, France

Location

Créteil Intercommunal Center

Créteil, 94010, France

Location

Lorient Hospital

Lorient, 56322, France

Location

Private clinic - Polyclinique de l'Atlantique

Nantes, 44819, France

Location

La Pitié Salpétrière Hospital (AP-HP)

Paris, 75010, France

Location

Robert Debré Hospital (AP-HP)

Paris, 75010, France

Location

Trousseau Hospital (AP-HP)

Paris, 75010, France

Location

Saint Joseph Hospital

Paris, 75014, France

Location

Poissy-Saint germain Hospital

Poissy, 78300, France

Location

Poitiers University Hospital

Poitiers, 86021, France

Location

Rennes University Hospital

Rennes, 35033, France

Location

Tours University Hospital

Tours, 37044, France

Location

Study Officials

• GRAS-LEGUEN Christele, PU-PH

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2015
• First Posted: October 28, 2015
• Study Start: May 3, 2016
• Primary Completion: January 22, 2017
• Study Completion: January 22, 2017
• Last Updated: September 20, 2019

Record last verified: 2019-09

Locations

FR (14)