Procalcitonin and Duration of AntiBiotherapy In Late Onset Sepsis of Neonate (PROABIS)

The duration of antibiotic (ATB) therapy in late onset sepsis (LOS) of the neonate is currently not based on scientific data. The current PROABIS trial will study the use of a biological marker, procalcitonin (PCT), to guide ATB therapy duration in neonates with LOS.

Our hypothesis is that the use of procalcitonin guidance can reduce of 30% the duration of ATB treatment without increasing recurrence of infection and mortality.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Randomized controlled multicenter open trial comparing the efficacy of PCT guided strategy (superiority aspect) and safety (non-inferiority aspect) versus usual strategy in LOS of the neonate.

After inclusion, patients are randomly assigned (in a 1:1 ratio) to duration of ATB therapy according to PCT guidance (experimental group) or to standard of care (control group).

Experimental group:

For patients randomly assigned in the PCT-guided group, a PCT concentration is measured at D0 (randomisation), at D2 and then, every two days until PCT value is equal or below 0.5 ng/mL.

The physician in charge of the neonate will be strongly encouraged to stop ATB treatment as soon as the PCT value is equal or below 0.5 ng/mL.

Control group:

In the control group, management of LOS and treatment are based on the attending clinician's practice and according to the usual practice (No PCT dosage).

In both groups data will be collected at the follow-up visit (day 14±2 after randomization) or the day of discharge from the hospital (if before 14±2 days) and at the end of the study visit (day 28± 2 after randomization) In case of transfer to another service or hospital or known re hospitalization before day28, outcomes will be collected from the service receiving the patient.

A phone call will be made to the parents, only in case of discharge before 28 days. following randomization. This phone call will be made 28± 2 days after randomization to identify adverse outcomes.

Study Type

Interventional

Enrollment (Actual)

511

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Tours
      • Paris, Tours, France, 37044
        • Department of Neonatology Bretonneau Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 days to 1 month (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Neonates born at 24 or more weeks of gestation,
  • Aged over 96 hours of life, i.e. from the 5th day of life and less than 45 gestational weeks at diagnosis of assumed or proven LOS,
  • Weight at the inclusion ≥ 700 g,
  • Treated by ATB therapy for less than 48 hours,
  • When the physician decides to continue de empiric ATB treatment beyond the initial 48-h period,
  • Written informed consent signed by both parents (in the absence of one of the two parents the day of inclusion, the new born can be included with the signature of only one parent.The second parent must give oral consent and sign the consent form as soon as possible "before day 28"),
  • Affiliation to a social security system (recipient or assign).

Exclusion Criteria:

  • Neonates with non-indication of ATB treatment following the 48h-initial empiric period.
  • ATB treatment within the 48h before the current episode of infection; except for taking antibiotics for prophylactic purposes (ex: digestive decontamination), pulmonary-targeted treatments for atypical germs and antibiotics by local means (ex.: eye drops).
  • Patients diagnosed with severe infections (meningitis and/or septic shock) or needing prolonged therapy (ex: endocarditis, bone infection, deep seated infection, abscesses). Septic shock is defined by fluid resistant hypotension requiring vasopressor therapy.
  • Infections not contracted during the hospitalization in the neonatal period or revealed more than 48 hours after hospital discharge.
  • Neonates during treatment by extracorporeal membrane oxygenation or extra-corporeal circulation, and within the 72h after the end of the treatment.
  • Neonates previously included in the Proabis study.
  • Participation with another interventional study involving human subjects or being in the exclusion period at the end of a previous study involving human subjects.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PCT-guided strategy
Measurement of PCT concentration will be performed every two days and the ATB therapy will be stopped when PCT level reaches a value equal or below 0.5ng/mL.
Measurement of PCT concentration will be performed every two days and the ATB therapy will be stopped when PCT level reaches a value equal or below 0.5ng/mL.
No Intervention: Usual practice (control group)
Management of LOS and treatment is based on the attending clinician's practice and according to the usual practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of the PCT guided ATB strategy on the duration of ATB treatment compared to usual ATB strategy
Time Frame: up to 28 days
Number of days between start and end of treatment, including treatment of the recurrence, if any
up to 28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Non-inferiority of the PCT-guided ATB strategy to usual strategy on mortality at 28 days following randomization
Time Frame: 28 days
Mortality rate at 28 days following randomization
28 days
Non-inferiority of the PCT-guided ATB strategy to usual strategy on recurrence of infection within 72 hours after ending ATB therapy.
Time Frame: 28 days
Proportion of infants with a treatment failure and recurrence of infection within 72h after ending ATB treatment and requiring additional course of ATBs.
28 days
Description on the total number of assumed or proven bacterial infections within the 28 days following randomization.
Time Frame: 28 days
Total number of assumed or proven bacterial infections within the 28 days following randomization, excluding the primary infection and its recurrence
28 days
To compare the cumulative dose of received ATB treatment (mg/kg).
Time Frame: Day 28
Cumulative dose of ATB treatment (mg/kg), defined as the total dose (in mg/kg) between start and end of treatment, including treatment of the recurrence, if any
Day 28
To describe the bacteriological epidemiology of LOS
Time Frame: 28 days
Recording of all the bacteriological species identified in blood or other samples during the LOS
28 days
Proportion of patients with bronchopulmonary dysplasia
Time Frame: 28 days
Proportion of patients with bronchopulmonary dysplasia in order to assess the proportion of patients with bronchopulmonary dysplasia at 28 days
28 days
Proportion of patients with at least one event between randomization and day 28 among death, recurrence of infection and bronchopulmonary dysplasia.
Time Frame: 28 days
Proportion of patients with at least one event between randomization and day 28 among death, recurrence of infection and bronchopulmonary dysplasia in order to evaluate the endpoint combining death or recurrence of infection or bronchopulmonary dysplasia
28 days
Antibiotics free days at D28
Time Frame: 28 days
Antibiotics free days at D28is defined as the number of days alive without any antibiotics at day 28.
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Delphine MITANCHEZ, PU-PH, Department of Neonatology Bretonneau Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 15, 2019

Primary Completion (Actual)

March 7, 2023

Study Completion (Actual)

March 7, 2023

Study Registration Dates

First Submitted

November 2, 2018

First Submitted That Met QC Criteria

November 2, 2018

First Posted (Actual)

November 5, 2018

Study Record Updates

Last Update Posted (Actual)

March 8, 2024

Last Update Submitted That Met QC Criteria

March 7, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

  • P 170928J
  • 2018-AO1396-49 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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