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ClinicalTrials.gov ID

NCT07791914

Lead Sponsor

Ulrikka NygaardOTHER

Overall Status

Not yet recruiting

Study Type

Interventional

Phase

Phase 4

Enrollment

150Estimated

Last Update Posted

Aug 28, 2026Actual

Start Date

Sep 1, 2026Estimated

Primary Completion Date

Nov 1, 2029Estimated

Completion Date

Nov 1, 2029Estimated

Official Title

Early Oral Switch Versus Intravenous Antibiotics in Previously Healthy Children and Adolescents With Bloodstream Infections

Brief Summary

This nationwide, multicenter, randomized, non-inferiority trial of children and adolescents with uncomplicated bloodstream infections aims to investigate if early-oral antibiotic switch (experimental arm) is non-inferior to standard intravenous antibiotics (control arm) with respect to treatment failure.

Detailed Description

Background:

Bloodstream infections are among the leading causes of hospital admission and prolonged intravenous (IV) antibiotic therapy in children and adolescents. Current international guidelines recommend IV-only or prolonged IV antibiotic therapy before an oral switch (1,2), but these recommendations rely primarily on historical convention and low-quality evidence rather than randomized controlled trials (RCTs) (1,2). Both adult and pediatric studies suggest that shorter IV courses followed by oral step-down therapy may be safe and effective across a range of serious infections. However, no RCT has explicitly investigated early oral switch in previously healthy children with bloodstream infections.

Objective:

The trial objective is to determine whether early IV-to-oral antibiotic switch, once clinically stable, is non-inferior to continued standard IV therapy with respect to treatment failure in previously healthy children and adolescents aged 4 weeks to 17 years with bloodstream infections.

Study design:

This is an investigator-initiated, nationwide, open-label, parallel-group, randomised (1:1), controlled, non-inferiority trial, with randomization stratified by pathogen group (Staphylococcus aureus, Gram-negative bacteria, and other bacteria).

Patients:

150 previously healthy children and adolescents aged 4 weeks to 17 years with bloodstream infections will be recruited from all 18 pediatric departments in Denmark.

Procedure:

Eligible children will be randomized 1:1 to an early oral switch strategy or standard IV therapy. The choice of oral and IV antibiotics will not be determined by randomization but will be made by the treating clinician according to the isolated pathogen, antimicrobial susceptibility, infectious focus and current treatment guidelines. The total antibiotic treatment duration will be the same in both treatment groups and determined by the site of infection, per Danish guidelines.

Participants allocated to the early oral switch arm (experimental arm) will switch to oral antibiotic therapy as soon as possible after clinical stability and within 4 days after initiation of effective IV antibiotic therapy. Children who have not received antibiotics, or who have received oral antibiotics before the blood culture becomes positive, may also be randomized to oral therapy; thus, prior IV therapy is not required in the experimental arm.

Participants allocated to the standard IV arm (control arm) will continue IV therapy for at least 5 days after initiation of effective IV antibiotic therapy, with 7 days recommended, followed by oral step-down if appropriate.

Sample size calculation:

The study aims to enroll a minimum of 150 participants. The sample size calculation is based on an expected treatment failure risk of 3% in both treatment arms, a non-inferiority margin of 10 percentage points, a one-sided alpha level of 2.5%, and the use of an appropriate statistical method that accounts for the expected low number of events. Assuming a dropout rate of up to 5%, enrollment of 150 participants will provide approximately 80% power to demonstrate non-inferiority.

Recruitment is planned for approximately 36 months and may be extended if required and feasible to achieve the target sample size. If 150 participants are enrolled within the initial 36-month recruitment period, enrollment will continue until the end of the 36-month recruitment period or until a maximum of 200 participants has been enrolled, whichever occurs first, to increase statistical power to approximately 90%.

• Bloodstream Infection
• Bacteremia Sepsis

• Oral antibiotic therapy
• Standard IV antibiotic therapy

Ages Eligible for Study

Child (0-17)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

INCLUSION CRITERIA

1. Age 4 weeks to 17 years
2. Positive blood culture with a i) pathogenic bacterium (eg, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Enterobacterales, Fusobacterium spp. and other pathogenic bacteria) or ii) preliminary blood culture result (eg, Gram-negative rods or Gram-positive cocci in clusters/chains) judged by the investigator to be clinically relevant (ie, not a contaminant) and for which IV antibiotic therapy would be indicated according to standard guidelines
3. Clinical stability, defined as: (a) respiratory and haemodynamic stability, without need for oxygen, IV fluid therapy or inotropic support; and (b) well-appearing with signs of clinical improvement (eg, improved physical activity), as judged by the investigator
4. Tolerating oral fluids and diet, as judged by the investigator
5. Within the randomization window (see below)
6. Informed consent obtained from a parent or guardian, and from the patient if aged 15 years or older

Randomization window:

Randomization will take place (1) as soon as possible after eligibility is confirmed, and (2) before completion of a maximum of 4 days (96 hours) of effective IV antibiotic therapy, including the duration of the last IV dose (eg, 8 hours for penicillin and 24 hours for ceftriaxone)

EXCLUSION CRITERIA

1. Complicated infections: a. Suspicion of endocarditis (echocardiography not performed routinely), b. Suspicion of CNS infection or post-septal cellulitis, c. Foreign material (eg, bone infection involving prosthetic material). d. Complicated postoperative course (eg, perforated appendicitis)
2. Blood culture positive with a. Neisseria meningitidis, b. Streptococcus pneumoniae if afebrile within 24 hours of blood culture collection, c. bacteria considered possible contaminants (eg, coagulase-negative staphylococci, Corynebacterium spp., Micrococcus spp.)
3. Premature infants with a corrected age of less than 28 days
4. No available suitable oral antibiotic (eg, due to antimicrobial resistance or contraindications)
5. Known chronic disease associated with an increased risk of severe infection: i) Immunosuppression, e.g., chemotherapy or biological therapy predisposing to severe infections, ii) Permanent central venous catheter due to an underlying condition, iii) Severe urinary tract abnormalities predisposing to bacteremia, including children receiving prophylactic antibiotic treatment.

Primary Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

Single

Lead Sponsor

Ulrikka NygaardOTHER

mette.holm@skejby.rm.dk

anders.egede.sandager.budtz@rsyd.dk

lisbeth.samsoe.schmidt@regionh.dk

brenda.masomi.kaaya@regionh.dk

paam@rn.dk

dva@regionsjaelland.dk

kathrine.work.havelund@rsyd.dk

sabine.froelich@midt.rm.dk

metnin@rm.dk