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

Primary Purpose

Early-Onset Neonatal Sepsis, Antibiotic Side Effect

Status
Recruiting
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Individualized treatment duration strategy
Sponsored by
Ulrikka Nygaard
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Early-Onset Neonatal Sepsis focused on measuring neonatal, early-onset, infection, antibiotic

Eligibility Criteria

1 Hour - 72 Hours (Child)All SexesDoes not accept 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

Sites / Locations

  • Ulrikka NygaardRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Individualized treatment duration

Standard treatment duration

Arm Description

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.

Standard treatment duration is seven days.

Outcomes

Primary Outcome Measures

Readmission due to infection.
Readmission due to infection, defined as symptoms, affected biomarkers and antibiotic treatment > 72 hours
Death
Death of any cause
Total use of antibiotics
Use of antibiotics (in hours)

Secondary Outcome Measures

C-reactive protein (CRP)
CRP (mg/l) levels at follow-up
Readmission due to infection within 3 months
Readmission due to infection, defined as symptoms, affected biomarkers and antibiotic treatment > 72 hours

Full Information

First Posted
April 7, 2022
Last Updated
June 26, 2022
Sponsor
Ulrikka Nygaard
Collaborators
Innovation Fund Denmark, University of Copenhagen
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1. Study Identification

Unique Protocol Identification Number
NCT05329701
Brief Title
Individualized Duration of Antibiotic Treatment in Early Onset Infection in Newborns.
Acronym
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.
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 22, 2022 (Actual)
Primary Completion Date
April 18, 2025 (Anticipated)
Study Completion Date
April 18, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ulrikka Nygaard
Collaborators
Innovation Fund Denmark, University of Copenhagen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Early-Onset Neonatal Sepsis, Antibiotic Side Effect
Keywords
neonatal, early-onset, infection, antibiotic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
488 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Individualized treatment duration
Arm Type
Experimental
Arm Description
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.
Arm Title
Standard treatment duration
Arm Type
No Intervention
Arm Description
Standard treatment duration is seven days.
Intervention Type
Other
Intervention Name(s)
Individualized treatment duration strategy
Intervention Description
As listed under arm description.
Primary Outcome Measure Information:
Title
Readmission due to infection.
Description
Readmission due to infection, defined as symptoms, affected biomarkers and antibiotic treatment > 72 hours
Time Frame
From 1-21 days after end of first course of antibiotic treatment.
Title
Death
Description
Death of any cause
Time Frame
From 1-21 days after end of first course of antibiotic treatment.
Title
Total use of antibiotics
Description
Use of antibiotics (in hours)
Time Frame
From initiation of antibiotics and the next 28 days.
Secondary Outcome Measure Information:
Title
C-reactive protein (CRP)
Description
CRP (mg/l) levels at follow-up
Time Frame
CRP measured at follow-up 2 days after initial antibiotic treatment ended
Title
Readmission due to infection within 3 months
Description
Readmission due to infection, defined as symptoms, affected biomarkers and antibiotic treatment > 72 hours
Time Frame
From 1-100 days after first course of antibiotics ended.
Other Pre-specified Outcome Measures:
Title
Hospital stay
Description
Length of hospital stay within 28 days after initial antibiotic treatment started
Time Frame
From initiation of antibiotics and the next 28 days.
Title
Positive blood cultures
Description
Numbers of culture positive infections
Time Frame
From 1-21 days after end of first course of antibiotic treatment.
Title
Serious adverse events (SAE)
Description
Any serious adverse events related to the study intervention
Time Frame
From initiation of antibiotics and the next 100 days.
Title
Total use of antibiotics
Description
Use of antibiotics (in hours)
Time Frame
From initiation of antibiotics and the next 100 days.
Title
Breastfeeding
Description
Exclusive and partial breastfeeding rates
Time Frame
At 2 day and 21 day follow up, after end of initial antibiotic treatment.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Hour
Maximum Age & Unit of Time
72 Hours
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Emma Malchau Carlsen, MD,PhD
Phone
+4527380508
Email
emma.louise.malchau.carlsen@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Ulrikka Nygaard, MD,PhD
Email
ulrikka.nygaard@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emma Malchau Carlsen, MD, PhD
Organizational Affiliation
Department of Neonatology, Rigshospitalet, Copenhagen, Denmark
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Tine Brink Henriksen, MD, Prof
Organizational Affiliation
Department of Neonatology, Skejby Sygehus, Aarhus, Denmark
Official's Role
Study Director
Facility Information:
Facility Name
Ulrikka Nygaard
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ulrikka Nygaard
Phone
40794656
Email
Ulrikka@dadlnet.dk

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Researchers who provide a methodologically sound proposal will be granted access to a full copy of individual deidentified data.
IPD Sharing Time Frame
The data will be available from 3 months after the publication of the study, ending 5 years after publication.
IPD Sharing 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).

Learn more about this trial

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

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