An open-label randomised controlled trial comparing novel combination and currently used antibiotic regimens for the empiric treatment of neonatal sepsis with a run-in confirmatory pharmacokinetic phase: NeoSep1
- Conditions
- Neonatal Diseases
- Registration Number
- PACTR202208856270989
- Lead Sponsor
- Global Antibiotic Research and Development Partnership GARDP
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- All
- Target Recruitment
- 3000
1. Currently admitted to hospital
2. Aged =28 days (post-natal age)
3. Weight =1000g
4. Clinical diagnosis of a new episode of sepsis together with planned treatment with IV
antibiotics
5. At moderate to high risk of death from this episode of sepsis, based on a neonatal sepsis
severity score (NeoSep Severity Score), adapted from the WHO PSBI based scores for the
hospital setting and developed using baseline clinical information and subsequent mortality
from the NeoOBS study as described in Table 5:5; specifically, a baseline assessment NeoSep
Severity Score of 5 or higher
6. Can receive at least 2 of the potential treatment options, ensuring randomisation is possible
(Part 2 only)
7. IV antibiotics about to be started OR not received more than 24 hours of IV antibiotics for
this episode of neonatal sepsis at the point of randomisation
8. Parent/guardian willing and able to provide consent (written or, if their baby is severely ill,
verbal consent confirmed by written consent as soon as possible). Verbal consent allows for
administration of first-line antibiotics at no or minimal delay (see Section 4.5 for details)
1. A known serious, non-infective co-morbidity including major congenital abnormalities (other
than prematurity), anticipated to cause death within this admission
2. Previously enrolled in this trial
3. Current participation in any other clinical study of an Investigational Medicinal Product (IMP)
that is a systemic drug, unless it has received prior approval by the NeoSep1 Trial
Management Group (TMG)
4. Known contraindication to any of the trial antibiotics on the randomisation list for the
relevant neonatal sub-population in that site (see Section 6; these will vary according to the
antibiotics on the specific randomisation list
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method For fosfomycin and flomoxef, the following primary pharmacokinetic (PK) parameters will be estimated from the population PK model:<br>• clearance (CL), central volume of distribution (V) <br>• postnatal maturation function parameters: fraction of size and scaled clearance at birth <br>(Fm) and the rate of postnatal maturation of clearance (Km)
- Secondary Outcome Measures
Name Time Method For fosfomycin and flomoxef, the following secondary PK parameters will be derived from the population PK model:<br>• Maximum plasma concentration (Cmax)<br>• Time to Cmax (Tmax)<br>• Apparent terminal elimination half-life (t1/2)Area under the plasma concentration-time curve from 0 to last observed time point (AUC0–last)<br>• Area Under the Curve to infinity (AUC(0–8))<br>• Volume of distribution at steady state (Vss)<br>Potential PK/PD relationships:<br>• Free drug AUC ratio to Minimum Inibitory Concentration (MIC) (fosfomycin)<br>• Fraction of time for free concentration above MIC (flomoxef)<br>Safety<br>• Adverse events (AEs) based on the International Neonatal Consortium Neonatal Adverse Event Severity Scale (NAESS) through Day 28<br>• Modification (including discontinuation) of antibiotics for adverse reactions