Efficacy, Pharmacokinetics and Safety of Meropenem in Infants Below 90 Days With Clinical or Confirmed Late-onset Sepsis (NeoMero-1)
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.
|Sepsis||Drug: Meropenem Drug: Ampicillin + gentamicin or cefotaxime + gentamicin||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Efficacy, Pharmacokinetics and Safety of Meropenem in Infants Below 90 Days of Age (Inclusive) With Clinical or Confirmed Late-onset Sepsis : a European Multicenter Randomised Phase III Trial|
- percentage of patients with a favorable outcome in the two arms [ Time Frame: an expected average of 14 days ]
The proportions of participants with a favourable outcome will be calculated in the meropenem arm and in the SOC arm. A favourable outcome is met when an infant:
- Is alive
- Has resolution or significant improvement of all abnormalities that defined LOS at entry and has no new clinical or laboratory abnormalities requiring a new course of antibiotic therapy
- Has microbiological eradication either confirmed or presumed and no new pathogens identified.
- Nature, frequency and numbers of clinical and biological adverse events [ Time Frame: 3 - 28 days ]Adverse events will also be summarised according to the need of a specific medical intervention or not. Analyses by time period will also be shown (from D0 to TOC visit and from TOC visit to follow-up). The number of patients experiencing at least one adverse event between D0 and TOC visit will be compared by treatment group.
|Study Start Date:||September 2012|
|Study Completion Date:||December 2014|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Infants will received the Meropenem 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.
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.
Other Name: Meropenem trihydrate
Active Comparator: Standard of care
The two accepted therapeutic options are:
Drug: Ampicillin + gentamicin or cefotaxime + gentamicin
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
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)
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.
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01551394
|Padova, Italy, 35128|
|Principal Investigator:||Ursula Trafojer||Clinica Pediatrica, Padova|
|Principal Investigator:||Irja Lutsar||University of Tartu, Estonia|
|Study Chair:||Jean-Pierre Aboulker||Institut National de la Santé Et de la Recherche Médicale, France|