Impact of Procalcitonin-guided Algorithm on Early Discontinuation of Antibiotic Therapy

Last updated: September 23, 2024
Sponsor: University Hospital, Toulouse
Overall Status: Active - Recruiting

Phase

N/A

Condition

Bacterial Infections

Treatment

Measurement of the PCT plasma levels

Usual practice based on guidelines

Clinical Study ID

NCT05350813
RC31/21/0334
2022-A00246-37
  • Ages 3-17
  • All Genders

Study Summary

In this randomized controlled open-label trial, conducted in 7 French Pediatric and Neonatal Intensive Care Units (ICUs), investigator team hypothesize that the use of a procalcitonin (PCT)-guided algorithm to discontinue antibiotic treatment will decrease antibiotic duration in critically ill children treated for a suspected or proven bacterial infection. Two hundred and ninety-six eligible patients will be randomly assigned in two groups: either PCT-guided or standard-of-care antibiotic discontinuation, and monitored over 28 days, until the end of their hospitalization, or up to the end of antibiotic treatment for bacterial infection recurrence occurring up to 28 days after the day of randomization.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Neonates, infants and children hospitalized in Pediatric and Neonatal ICU andreceiving intravenous antibiotics for less than 24 hours for an episode of suspectedor proven community-acquired or nosocomial bacterial infection.

  • Written informed consent signed by both parents or legal guardians.

  • Affiliated to a social security scheme.

  • Parents French-speaking.

Exclusion

Exclusion Criteria:

  • Newborns <72 hours old.

  • Neonates <37 weeks postmenstrual age.

  • Age ≥18 years.

  • Pregnant or breastfeeding women.

  • Patients with cystic fibrosis.

  • Immunocompromised patients including patients with hereditary immunodeficiency,agranulocytosis (neutrophils count <500/mm3), HIV infection with CD4 count <200/mm3,sickle cell disease, those who have undergone splenectomy, those who have a historyof solid organ or hematopoietic stem cell transplant, those with hemopathy or solidorgan tumor treated with chemotherapy, and those on immunosuppressive drugsincluding systemic corticosteroids taken daily for at least 15 days prior to Day 0.

  • Inflammatory situations increasing PCT plasma concentrations in the absence ofinfection: burns, extracorporeal membrane oxygenation (ECMO), first 48 hoursfollowing an open-heart cardiac surgery with cardiopulmonary bypass.

  • Infections requiring prolonged antibiotic therapy: infected thrombophlebitis,infective endocarditis, mediastinitis, abscess or empyema (e.g. peritonsillarabscess, retropharyngeal abscess, adenophlegmon, retroauricular abscess,retroorbital abscess, pulmonary abscess, pleural empyema, liver abscess, splenicabscess, brain abscess, subdural empyema, extradural empyema, epidural abscess,intramuscular abscess), necrotizing dermohypodermitis or necrotizing fasciitis,osteomyelitis, osteitis, arthritis, spondylodiscitis, prostatitis, tuberculosis,meningitis except those caused by Haemophilus and Meningococcus, infection on adevice excluding intravascular catheter, endotracheal tube, tracheostomy, andurinary catheter.

  • Antibiotic for prophylaxis.

  • Children previously included in an interventional study in progress.

Study Design

Total Participants: 296
Treatment Group(s): 2
Primary Treatment: Measurement of the PCT plasma levels
Phase:
Study Start date:
May 02, 2023
Estimated Completion Date:
February 02, 2027

Study Description

Infections are widespread in Pediatric and Neonatal ICU, and antibiotic treatments widely used. Long courses of antibiotic treatment increase the duration of hospitalization and are associated with changes in the microbiome, emergence of multidrug resistant organisms, and antibiotic-associated adverse events. In Pediatric and Neonatal ICU, PCT has a high negative predictive value to rule out bacterial infection. Thus, in sepsis patients and patients who initially appear to have sepsis but whose final diagnosis of bacterial infection is not retained, the use of a PCT-guided algorithm may be of value to shorten antibiotic duration without increasing infection recurrences. The algorithm has provided strong evidence of efficacy and safety among critically ill adults, excluding immunocompromised patients, patients with cystic fibrosis, and infections requiring prolonged antibiotic therapy. Similar data in critically ill children are lacking. A Spanish team from Sant Joan de Déu published three prospective non-randomized studies in Pediatric ICU (PICU), with encouraging results. Only one American randomized controlled trial (RCT) has been published in PICU with mixed results. One RCT is ongoing in India. Thus, our study will be the first French RCT to study the use of a PCT-guided algorithm to de-escalate antibiotic therapy in PICU, in order to provide evidence of efficacy and safety of such an algorithm in critically ill children with a suspected or proven bacterial infection. In addition, investigator team will also study the economic impact of a PCT-guided algorithm which has never been done before.

In the PCT-guided arm, PCT dosage will be done at Day 0 (day of randomization) and Day 1, and then every 48 hours until cessation of antibiotics in hospital or discharge from hospital if the patient is discharged with an antibiotic treatment. Antibiotic treatment will be stopped according to PCT value and patient clinical evolution. In the control group, antibiotic duration will be determined by usual practices based on guidelines. Inpatient evaluations will be conducted every day so long as patients receives antibiotics in hospital and usual clinical, biological and/or radiological monitoring will be conducted in both groups. To monitor infection recurrence occurring up to 28 days after the day of randomization and antibiotic-related adverse events, an evaluation will be conducted at the end of hospitalization, another at Day 28 (Day 0 = day of randomization), and a last at the end of antibiotic treatment bacterial infection recurrence, if the patient is discharged from hospital on or before Day 28 and is still treated with antibiotics for a bacterial infection recurrence at Day 28, or if the patient is discharged from hospital after Day 28 and is still treated for recurrence on the last day of hospitalization with antibiotics for a bacterial infection recurrence.

Connect with a study center

  • CHU Amiens Picardie

    Amiens,
    France

    Site Not Available

  • CHU de Bordeaux

    Bordeaux,
    France

    Site Not Available

  • CHU de Clermont Ferrand

    Clermont-Ferrand,
    France

    Active - Recruiting

  • CHU de NANTES

    Nantes,
    France

    Active - Recruiting

  • APHP

    Paris,
    France

    Site Not Available

  • CHU La Réunion

    Saint-Denis,
    France

    Active - Recruiting

  • University Hospital of Toulouse

    Toulouse, 31100
    France

    Active - Recruiting

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