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

Antibiotic Side Effect Clinical Trial

— DurATi-n  

Official title:

Individualized Duration of Antibiotic Treatment in Culture Negative Early Onset Infection in Term Born Newborns: A Nationwide Randomized Controlled Non-inferiority Trial.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05329701
• Other study ID #: H-21004823
• Status: Recruiting
• Phase: Phase 4
• Start date: April 22, 2022
• Est. completion date: April 18, 2028

Study information

• Verified date: June 2022
• Source: Rigshospitalet, Denmark
• Contact: Emma Malchau Carlsen, MD,PhD
• Phone: +4527380508
• Email: emma.louise.malchau.carlsen[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 488
• Est. completion date: April 18, 2028
• Est. primary completion date: April 18, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 72 Hours

Eligibility

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

Related Conditions & MeSH terms

• Antibiotic Side Effect
• Early-Onset Neonatal Sepsis
• Infections
• Neonatal Sepsis

Intervention

Other:
• Individualized treatment duration strategy
As listed under arm description.

Locations

Country	Name	City	State
Denmark	Ulrikka Nygaard	Copenhagen

Sponsors (3)

Lead Sponsor	Collaborator
Ulrikka Nygaard	Innovation Fund Denmark, University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hospital stay	Length of hospital stay within 28 days after initial antibiotic treatment started	From initiation of antibiotics and the next 28 days.
Other	Positive blood cultures	Numbers of culture positive infections	From 1-21 days after end of first course of antibiotic treatment.
Other	Serious adverse events (SAE)	Any serious adverse events related to the study intervention	From initiation of antibiotics and the next 100 days.
Other	Total use of antibiotics	Use of antibiotics (in hours)	From initiation of antibiotics and the next 100 days.
Other	Breastfeeding	Exclusive and partial breastfeeding rates	At 2 day and 21 day follow up, after end of initial antibiotic treatment.
Primary	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.
Primary	Death	Death of any cause	From 1-21 days after end of first course of antibiotic treatment.
Primary	Total use of antibiotics	Use of antibiotics (in hours)	From initiation of antibiotics and the next 28 days.
Secondary	C-reactive protein (CRP)	CRP (mg/l) levels at follow-up	CRP measured at follow-up 2 days after initial antibiotic treatment ended
Secondary	Readmission due to infection within 3 months	Readmission due to infection, defined as symptoms, affected biomarkers and antibiotic treatment > 72 hours	From 1-100 days after first course of antibiotics ended.