eoSep1: a study to determine the ranking of existing and new antibiotics combinations to treat newborn babies who are in hospital with severe sepsis

Phase 2

• Conditions: eonatal sepsis; Infections and Infestations

• Registration Number: ISRCTN48721236
• Lead Sponsor: Global Antibiotic Research & Development Partnership

Brief Summary

2024 Poster results see attached file ISRCTN48721236 NeoSEP Part1 results ESPID poster_30Apr24.pdf Part 1 results (added 10/06/2024)

Detailed Description

Not available

Study Timeline

• Study Start: 2022-02-24
• Last Update Posted: 24 June 2024
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 3060

Inclusion Criteria

1. Currently admitted to hospital
2. Aged =28 days (post-natal age)
3. Weight >1000 g
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) developed using baseline clinical information and subsequent mortality from the NeoOBS study; specifically, a baseline assessment NeoSep Severity Score of 4 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 >24 h 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 the administration of first-line antibiotics at no or minimal delay.

Exclusion Criteria

1. A 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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Part 1:<br>1. PK parameters derived for fosfomycin and flomoxef using the population PK model using Day 1 PK samples taken at 5 min, 30 min, and 4 h post-treatment or 15 min, 1 h, and 6 h post-treatment from the population:<br>1.1. Clearance (CL)<br>1.2. Central volume of distribution (V)<br>1.3. Postnatal maturation function parameters: fraction of size and scaled clearance at birth (Fm) and the rate of postnatal maturation of clearance (Km)<br><br>Part 2:<br>1. 28-day mortality  measured from patient records at 28 days