DurATi-n: Individualized Duration of Antibiotic Treatment in Early Onset Infection in Newborns.
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Individualized treatment duration Antibiotic treatment will be discontinued when both of the following two criteria are fulfilled: The infant has had 24 hours without clinical symptoms of infection, after systematic clinical evaluation by a neonatologist. Clinical symptoms specified in Table 1. 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
As listed under arm description.
|
| No Intervention: Standard treatment duration Standard treatment duration is seven days. |
Outcome Measures
Primary Outcome Measures
- Readmission due to infection. [From 1-21 days after end of first course of antibiotic treatment.]
Readmission due to infection, defined as symptoms, affected biomarkers and antibiotic treatment > 72 hours
- Death [From 1-21 days after end of first course of antibiotic treatment.]
Death of any cause
- Total use of antibiotics [From initiation of antibiotics and the next 28 days.]
Use of antibiotics (in hours)
Secondary Outcome Measures
- C-reactive protein (CRP) [CRP measured at follow-up 2 days after initial antibiotic treatment ended]
CRP (mg/l) levels at follow-up
- Readmission due to infection within 3 months [From 1-100 days after first course of antibiotics ended.]
Readmission due to infection, defined as symptoms, affected biomarkers and antibiotic treatment > 72 hours
Other Outcome Measures
- Hospital stay [From initiation of antibiotics and the next 28 days.]
Length of hospital stay within 28 days after initial antibiotic treatment started
- Positive blood cultures [From 1-21 days after end of first course of antibiotic treatment.]
Numbers of culture positive infections
- Serious adverse events (SAE) [From initiation of antibiotics and the next 100 days.]
Any serious adverse events related to the study intervention
- Total use of antibiotics [From initiation of antibiotics and the next 100 days.]
Use of antibiotics (in hours)
- Breastfeeding [At 2 day and 21 day follow up, after end of initial antibiotic treatment.]
Exclusive and partial breastfeeding rates
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ulrikka Nygaard | Copenhagen | Denmark | 2100 |
Sponsors and Collaborators
- Ulrikka Nygaard
- Innovation Fund Denmark
- University of Copenhagen
Investigators
- Principal Investigator: Emma Malchau Carlsen, MD, PhD, Department of Neonatology, Rigshospitalet, Copenhagen, Denmark
- Study Director: Tine Brink Henriksen, MD, Prof, Department of Neonatology, Skejby Sygehus, Aarhus, Denmark
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- H-21004823