Individualized Duration of Antibiotic Treatment in Early Onset Infection in Newborns.

NCT05329701 | Completed Phase 4 DMC

• 1 other identifier: H-21004823
• Study Type: interventional
• Target: 488
• Locations: 1 country
• Sites: 1

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.

Conditions

Early-Onset Neonatal Sepsis; Antibiotic Side Effect

Keywords

neonatal; early-onset; infection; antibiotic

Outcome Measures

Primary Outcomes (3)

• Readmission due to infection.

  Readmission due to infection, defined as symptoms, affected biomarkers and antibiotic treatment \> 72 hours

  From 1-21 days after end of first course of antibiotic treatment.

• Death

  Death of any cause

  From 1-21 days after end of first course of antibiotic treatment.

• Total use of antibiotics

  Use of antibiotics (in hours)

  From initiation of antibiotics and the next 28 days.

Secondary Outcomes (2)

• C-reactive protein (CRP)

  CRP measured at follow-up 2 days after initial antibiotic treatment ended

• Readmission due to infection within 3 months

  From 1-100 days after first course of antibiotics ended.

Other Outcomes (5)

• Hospital stay

  From initiation of antibiotics and the next 28 days.

• Positive blood cultures

  From 1-21 days after end of first course of antibiotic treatment.

• Serious adverse events (SAE)

  From initiation of antibiotics and the next 100 days.

Study Arms (2)

Individualized treatment duration

EXPERIMENTAL

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.

Other: Individualized treatment duration strategy

Standard treatment duration

NO INTERVENTION

Standard treatment duration is seven days.

Interventions

Individualized treatment duration strategy OTHER

As listed under arm description.

Individualized treatment duration

Eligibility Criteria

• Age: 1 Hour - 72 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ulrikka Nygaard: lead
• Innovation Fund Denmark: collaborator
• University of Copenhagen: collaborator

Study Sites (1)

Ulrikka Nygaard

Copenhagen, 2100, Denmark

Location

MeSH Terms

Conditions

Neonatal Sepsis; Infections

Condition Hierarchy (Ancestors)

Sepsis; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Emma Malchau Carlsen, MD, PhD

  Department of Neonatology, Rigshospitalet, Copenhagen, Denmark

  PRINCIPAL INVESTIGATOR

• Tine Brink Henriksen, MD, Prof

  Department of Neonatology, Skejby Sygehus, Aarhus, Denmark

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD,Phd, Consultant, Associate Professor

Model Details: 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.

Study Record Dates

• First Submitted: April 7, 2022
• First Posted: April 15, 2022
• Study Start: April 22, 2022
• Primary Completion: April 5, 2025
• Study Completion: August 10, 2025
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The data will be available from 3 months after the publication of the study, ending 5 years after publication.
• Access Criteria: Proposals should be directed to the corresponding author of this article, and access can be granted after the proposal is approved by the trial steering committee. Data will be available at a third party website after a data access agreement is signed (link to website will be shared after request is approved).

Locations

DK (1)