Efficacy, Pharmacokinetics and Safety of Meropenem in Infants Below 90 Days With Clinical or Confirmed Late-onset Sepsis
Condition: Sepsis
MeSH terms: Sepsis; Toxemia
Study type: Interventional
Phase: Phase 3

Summary: 
      This phase III multicentric international randomized trial is designed to compare the
      efficacy of Meropenem to the standard of care in infants below 90 days of age with clinical
      or confirmed late-onset sepsis (LOS).

      The aim is to assess efficacy , pharmacokinetics and safety of Meropenem which are not well
      known and documented in this population.
    

Detailed description: 
      The principal objective is to compare the efficacy at test of cure (TOC) visit of meropenem
      to the standard of care (SOC) in the treatment of clinical or confirmed LOS in infants ≤ 90
      days of postnatal age.

      The secondary objectives are:

        -  To compare the safety profile of meropenem to SOC

        -  To compare the efficacy at TOC visit of meropenem to SOC in confirmed sepsis

        -  To compare the response to meropenem and SOC on day 3 of antibacterial therapy

        -  To compare the efficacy at TOC visit of meropenem to SOC ignoring the change of
           antibiotic(s) for safety reasons

        -  To compare the efficacy at TOC visit of meropenem to SOC by SOC regimen

        -  To compare survival at follow up (FU) visit (28 day visit) in the meropenem arm and SOC
           arm

        -  To compare new infections and relapses that occur between TOC and FU visits in
           participants with a favourable outcome at TOC visit by treatment arm

        -  To define the organisms causing LOS

        -  To study antibacterial susceptibility of LOS-causing organisms and to describe clinical
           and microbiological responses according to this

        -  To compare gut colonization by antibiotic resistant organisms after treatment with
           meropenem or SOC

        -  To compare bacterial eradication by treatment arm

        -  To compare time to NICU discharge across the 2 arms

        -  To describe PK of meropenem in infants ≤ 90 days of postnatal age with LOS

        -  To evaluate genetic parameters that may affect response to therapy
    

Intervention name(s): Meropenem; Ampicillin + gentamicin or cefotaxime + gentamicin
Intervention type(s): Drug; Drug
Intervention description(s): 20 mg/kg every 8 hours (every 12 hours in the youngest age group: < 32 weeks GA and < 2 weeks postnatal age). The dose will be given as an infusion over 30 minutes. Treatment duration is 11 ± 3 days.; Ampicillin:
Neonates below 7 days: 50mg/kg every 12 hours Neonates 7-21 days: 50mg/kg every 8 hours Neonates and Infants from day 22 on: 50mg/kg every 6 hours
Gentamicin:
Neonates less than 32 weeks of corrected age: 5mg/kg every 36 hours Neonates 32 weeks and over of corrected age: 5mg/kg every 24 hours (pre-dose ('trough') concentrations should be less than 2mg/l) Infants over 28 days of postnatal age: once daily dose: initially 5-7mg/kg, then adjust according to serum-gentamicin concentration (pre-dose ('trough') concentrations should be less than 1mg/l)
Cefotaxime:
Neonates below 7 days of PNA: 50mg/kg every 12 hours Neonates and infants from day 7 of PNA: 50mg/kg every 8 hours Treatment duration is 11 ± 3 days.
Other intervention name(s): Meropenem trihydrate; Ampicillin sodium; Gentamicin sulphate; Cefotaxime sodium
Intervention MeSH terms: Gentamicins; Meropenem; Ampicillin; Cefotaxime; Cefoxitin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: sepsis; neonates; meropenem