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

NCT ID: NCT05350813

Last Updated: 2024-09-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 296 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-02
• Study Completion Date: 2027-02-02

Brief 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.

Detailed 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.

Conditions

Bacterial Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

PCT-guided arm

Group of patients whose duration of antibiotic therapy will depend on procalcitonin (PCT) plasma levels on days 0 and 1, then on PCT plasma level every 48 hours and on patient clinical evolution evaluated by the fever, the infected organ, and the pSOFA (Pediatric Sequential Organ Failure Assessment) score every day until cessation of antibiotics in hospital or until discharge from hospital if the patient is discharged with an antibiotic treatment.

Group Type: EXPERIMENTAL

Measurement of the PCT plasma levels

Intervention Type: PROCEDURE

antibiotic treatment duration will be based on PCT plasma levels

standard-of-care arm

A group of patients whose duration of antibiotic therapy will be determined by the type of infection, microbiological findings and clinical, biological and/or radiological course, according to standard practice based on guidelines.

Group Type: ACTIVE_COMPARATOR

Usual practice based on guidelines

Intervention Type: PROCEDURE

antibiotic therapy duration will be determined by the type of infection, microbiological results and clinical, biological and/or radiological evolution, according to the usual practice based on guidelines.

Interventions

Measurement of the PCT plasma levels

antibiotic treatment duration will be based on PCT plasma levels

Intervention Type: PROCEDURE

Usual practice based on guidelines

antibiotic therapy duration will be determined by the type of infection, microbiological results and clinical, biological and/or radiological evolution, according to the usual practice based on guidelines.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Neonates, infants and children hospitalized in Pediatric and Neonatal ICU and receiving intravenous antibiotics for less than 24 hours for an episode of suspected or 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 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 history of solid organ or hematopoietic stem cell transplant, those with hemopathy or solid organ tumor treated with chemotherapy, and those on immunosuppressive drugs including systemic corticosteroids taken daily for at least 15 days prior to Day 0.
• Inflammatory situations increasing PCT plasma concentrations in the absence of infection: burns, extracorporeal membrane oxygenation (ECMO), first 48 hours following an open-heart cardiac surgery with cardiopulmonary bypass.
• Infections requiring prolonged antibiotic therapy: infected thrombophlebitis, infective endocarditis, mediastinitis, abscess or empyema (e.g. peritonsillar abscess, retropharyngeal abscess, adenophlegmon, retroauricular abscess, retroorbital abscess, pulmonary abscess, pleural empyema, liver abscess, splenic abscess, 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 a device excluding intravascular catheter, endotracheal tube, tracheostomy, and urinary catheter.
• Antibiotic for prophylaxis.
• Children previously included in an interventional study in progress.

• Minimum Eligible Age: 3 Days
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Romain AMADIEU, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Toulouse

Locations

CHU Amiens Picardie

Amiens, , France

Site Status: ACTIVE_NOT_RECRUITING

CHU de Bordeaux

Bordeaux, , France

Site Status: ACTIVE_NOT_RECRUITING

CHU de Clermont Ferrand

Clermont-Ferrand, , France

Site Status: RECRUITING

CHU de NANTES

Nantes, , France

Site Status: RECRUITING

APHP

Paris, , France

Site Status: ACTIVE_NOT_RECRUITING

CHU La Réunion

Saint-Denis, , France

Site Status: RECRUITING

University Hospital of Toulouse

Toulouse, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Romain AMADIEU, MD

Role: CONTACT

amadieu.r@chu-toulouse.fr

053-455-7495

Gwennaëlle ALPHONSA

Role: CONTACT

alphonsa.g@chu-toulouse.fr

056-777-1394

Facility Contacts

Nadia SAVY, MD

Role: primary

Brendan TRAVERT, MD

Role: primary

Pauline DUPORT, MD

Role: primary

Armelle BRIDIER, MD

Role: primary

Other Identifiers

2022-A00246-37

Identifier Type: OTHER

Identifier Source: secondary_id

RC31/21/0334

Identifier Type: -

Identifier Source: org_study_id