Trial | NCT03247920  Report issue

Title

Reduction of Intravenous Antibiotics In Neonates
Intravenous to Oral Antibiotic Switch Therapy for Probable Neonatal Bacterial Infections: Clinical Efficacy, Safety and Cost-effectiveness

  • Phase

    Phase 4

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    510
Randomized controlled open-label non-inferiority trial comparing complete intravenous antibiotic treatment with a short iv. course followed by oral antibiotics in neonates (0-28 days) with probable bacterial infection.

Primary outcome:

- Bacterial re-infection within 28 days after finishing of antibacterial therapy.

Secondary outcome(s):

Pharmacokinetic profile of oral amoxicillin/clavulanic acid
Quality of life
Cost-effectiveness
Alterations in gut microbiome
Use of molecular techniques for better detection of bacterial pathogens
Neonates have a high antibiotic consumption because of their susceptibility for bacterial infections. Since the early diagnosis of bacterial infection in neonates is difficult, intravenous broad-spectrum antimicrobial therapy is usually started promptly after subtle symptoms. The majority of neonates become asymptomatic shortly after initiation; when infection is probable or proven by elevated inflammatory markers and/or a positive blood culture, intravenous antibiotics are administered for at least 7 days.

However, for neonates blood culture has a limited sensitivity. Therefore, the majority of neonates with probable infection are treated for a prolonged time with intravenous broad-spectrum antimicrobial therapy. In older children, intravenous antibiotics are often changed to oral antibiotics after cessation of symptoms and decreasing inflammatory parameters. This is not yet widely practised in neonates because of uncertainties in pharmacokinetics. Two explorative small studies from France and Italy into neonatal antibiotic switch therapy suggest that follow-up treatment with an oral antibiotic is promising; but the non-inferiority and safety was not yet properly addressed. Neonatal switch therapy, if proven to be safe and efficacious, would have a major impact on neonatal well-being, mother-to-child bonding and moreover costs.
Study Started
Nov 04
2017
Primary Completion
Jun 15
2021
Study Completion
Jul 15
2021
Last Update
Aug 24
2021

Drug Amoxicillin Clavulanate [amoxicillin, clavulanate (Augmentin)]

Dose 75 mg/kg/day, (3dd 25 mg/kg). Concentration amoxicillin/clavulanic acid: 4:1

Drug Antibiotics

Intravenous antibiotic therapy following local protocol

Oral group Active Comparator

After 48 hours of intravenous antibiotics eligible neonates will switch to amoxicillin/clavulanic acid suspension for the remaining 5 days. When the oral suspension is well tolerated neonates can be discharged from hospital. In order to investigate the pharmacokinetic profile of oral amoxicillin/clavulanic acid serum levels will be measured.

Intravenous group Active Comparator

Neonates will complete the full course of antibiotics of 7 days intravenously in hospital following local protocol.

Criteria 

Inclusion Criteria:

Neonates (≥ 35+0 weeks, 0-28 days old, ≥ 2 kg)
Probable bacterial infection defined as clinical symptoms and/or maternal risk factors and elevated inflammatory markers for which empiric broad-spectrum antibiotic treatment was initiated and needs to be continued for > 48 hours
Clinically well
Toleration of oral feeding without overt vomiting
Signed informed consent

Exclusion Criteria:

Proven bloodstream infection
Absence of blood culture
Severe localized infection (meningitis, osteomyelitis, necrotizing enterocolitis)
Severe clinical sepsis (compromised circulation, need for mechanical ventilation)
Continuous need for a central venous line
Severe hyperbilirubinemia exceeding the exchange level
Parents inability to administer medication
Major congenital or syndromic anomalies
No Results Posted