Individualized Duration of Antibiotic Treatment in Early Onset Infection in Newborns. (DurATi-n)

Ulrikka Nygaard

Status and phase: Enrolling; Phase 4

Conditions: Antibiotic Side Effect; Early-Onset Neonatal Sepsis

Treatments: Other: Individualized treatment duration strategy

Study type: Interventional

Funder types: Other

Identifiers

NCT05329701

H-21004823

Details and patient eligibility

About

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.

Full 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.

Enrollment: 488 estimated patients

Sex: All

Ages: 1 to 72 hours old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

488 participants in 2 patient groups

Individualized treatment duration

Experimental group

Description:

Antibiotic treatment will be discontinued when both of the following two criteria are fulfilled: 1. The infant has had 24 hours without clinical symptoms of infection, after systematic clinical evaluation by a neonatologist. Clinical symptoms specified in Table 1. 2. CRP is \< 30 mg/l. If CRP is \> 30 at the time when the infant has been symptom-free for 24 hours, CRP will be assessed once every 24 -48 hours and antibiotics will be stopped when CRP \< 30.

Treatment:

Other: Individualized treatment duration strategy

Standard treatment duration

No Intervention group

Description:

Standard treatment duration is seven days.