Clinical trial NCT05329701: Individualized Duration of Antibiotic Treatment in Early Onset Infection in Newborns.
Official title: Individualized Duration of Antibiotic Treatment in Culture Negative Early Onset Infection in Term Born Newborns: A Nationwide Randomized Controlled Non-inferiority Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Early-Onset Neonatal Sepsis
Antibiotic Side Effect
Keywords: neonatal
early-onset
infection
antibiotic
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Innovation Fund Denmark
name: University of Copenhagen
First posted: 2022-04-15
Enrollment: 488
Sex: ALL
Minimum age (years): 1
Maximum age (years): 72
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study is a nationwide multicenter open label non-inferiority pragmatic randomized controlled trial. Patients will be randomized 1:1 to experimental treatment duration or standard care. Patients will be stratified based on if maximum CRP level is above or below 90 mg/l.
Primary purpose: TREATMENT

Brief summary: A nationwide multicenter open label randomized controlled non-inferiority trial, including 18 departments. The study aims to compare an individualized antibiotic treatment duration with standard seven days of antibiotic treatment for culture negative early-onset infection in term newborns.

Detailed description: There is a documented antibiotic overuse in newborns, and a lack of evidence for the optimal duration of antibiotic therapy in culture-negative infection. The study aims to evaluate the effect of individualized treatment duration in early-onset infection.

The study aims to compare an individualized treatment duration with seven days of treatment for culture negative early-onset infection. The investigators hypothesize that the individualized treatment duration, based on structured clinical assessment of symptoms and level of CRP is non-inferior to the standard care being seven days of treatment. In the experimental treatment arm, antibiotics will be stopped when the participant had 24 hours without symptoms and at same time point have decreasing level of CRP, with an absolute threshold of CRP ≤ 30 mg/l. The investigators hypothesize that individualized treatment will shorten the duration of antibiotic therapy in newborns with early onset infection with very little risk of relapse. Newborns who fulfill criteria to stop antibiotics within 48 hours will not be eligible for inclusion.

Eligibility criteria: Inclusion Criteria:

* Gestational age ≥ 35 weeks
* Birth weight ≥ 2000
* Probable or possible infection according to the structured infection risk assessment
* Sufficient size blood culture, preferably 0.5-1 ml, but at least 0.2 ml, drawn after onset of symptoms but before start of antibiotic treatment
* Negative blood culture after 48 hours

Exclusion Criteria:

* Infants with positive blood culture
* Blood culture volume prior to antibiotics of \< 0.2 ml
* Site-specific infection as for example, meningitis or osteomyelitis
* Infant fulfill current recommendation to stop antibiotic treatment at 36-48 hours; Low suspicion of sepsis initially including few and vague symptoms, CRP maximum 35-50 mg/l, negative blood culture and no symptoms after 48 hours of treatment

Primary outcomes:
measure: Readmission due to infection.
timeFrame: From 1-21 days after end of first course of antibiotic treatment.
measure: Death
timeFrame: From 1-21 days after end of first course of antibiotic treatment.
measure: Total use of antibiotics
timeFrame: From initiation of antibiotics and the next 28 days.
Secondary outcomes:
measure: C-reactive protein (CRP)
timeFrame: CRP measured at follow-up 2 days after initial antibiotic treatment ended
measure: Readmission due to infection within 3 months
timeFrame: From 1-100 days after first course of antibiotics ended.
Other outcomes:
measure: Hospital stay
timeFrame: From initiation of antibiotics and the next 28 days.
measure: Positive blood cultures
timeFrame: From 1-21 days after end of first course of antibiotic treatment.
measure: Serious adverse events (SAE)
timeFrame: From initiation of antibiotics and the next 100 days.
measure: Total use of antibiotics
timeFrame: From initiation of antibiotics and the next 100 days.
measure: Breastfeeding
timeFrame: At 2 day and 21 day follow up, after end of initial antibiotic treatment.
Locations:
city: Copenhagen
country: Denmark
facility: Ulrikka Nygaard
Study officials:
affiliation: Department of Neonatology, Rigshospitalet, Copenhagen, Denmark
name: Emma Malchau Carlsen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Neonatology, Skejby Sygehus, Aarhus, Denmark
name: Tine Brink Henriksen, MD, Prof
role: STUDY_DIRECTOR
References: