Introduction

Newborn babies are vulnerable to infections caused by bacteria, so antibiotics are given as soon as a doctor suspects an infection. 

Infections needing antibiotics, despite negative lab results, are common. The bacteria or other pathogen causing the infection is often hard to identify, but the infant needs treatment urgently. There are many different antibiotics used to treat infections in babies, and it is often unclear which is best to prescribe. Antibiotics can be given at different doses, lengths of time, and in different combinations – but it is not always known antibiotic regimens which work best in the neonatal population.

A certain antibiotic, dose or length of treatment could be problematic because the good bacteria living in the baby’s gut could be altered or become resistant to antibiotics. Antibiotics may then not work as well for future infections if the resistant bacteria spreads. Therefore, it is essential that research about optimal antibiotic management of neonatal infections is designed and delivered to understand the best treatment approach and improve the clinical outcomes of these unwell infants.

Challenges in Clinical Trials

The best way to study treatments is in a clinical trial, which is often challenging with unwell or very premature newborns. Parents and healthcare professionals find infections worrying and struggle to consider whether it is right for their baby or patient to take part in research. Babies with different problems are looked after on neonatal units, for example those born too early or those with surgical conditions. This makes it difficult to decide whether a certain antibiotic, dose or treatment length will work well for each individual baby. Also, identifying any unwanted effects of a treatment is hard because babies on neonatal units may have other problems and it is not clear which are related to the trial treatment.

This project will aim to work out how some of these challenges can be addressed when designing a new clinical trial investigating optimal antibiotic management of neonatal sepsis. National and international academic experts, as well as parents and healthcare professionals from UK-based neonatal units, will be recruited to interviews and focus groups to gather their lived experiences of the neonatal unit. This data will be used to inform a set of guidelines and tools that can be used by researchers in the field to ensure the priorities of future research studies are aligned with the needs of parents, healthcare professionals, and trial teams. Ultimately, these types of trial will help to identify the best treatments for newborns on the neonatal unit, resulting in improved health and clinical outcomes.

Adapative Platform Trials

The NeoSep-ADAPT trial will be a special kind of trial that can be used to answer many questions for babies with different characteristics at the same time, called an adaptive platform trial. An adaptive platform trial is suitable when doctors have many possible treatment options, but it is not known which is the best for a specific baby.

In a regular trial, the decisions about how the trial will be run are decided before it starts. However, in an adaptive trial it is possible to change the treatments that are being studied, as well as how many babies receive each of the treatments, when the trial is already running. This is a very unique trial design, which was used throughout the COVID-19 trials, and would also be a suitable design to look at the different antibiotics which might be best to treat neonatal infections.

During the trial, any treatment changes are made based on a set of rules from collected information from babies already in the study which assesses how well they are doing. This makes it possible to target better performing treatments to more babies and to eventually drop treatments that are not working so well. Adaptive trials tend to be faster and more efficient, which should hopefully result in better treatments being made available more quickly.