SNIP-AFRICA

The challenge

Sepsis is one of the most common causes of death of neonates and young infants – globally, it is responsible for more than two million deaths a year. It is one reason why the number of neonatal deaths has shown only a small recent decline, despite a significant fall in wider child mortality.

Sepsis is a clinical challenge because it can be triggered by a range of different infections, requiring different treatments. Some of these infections can be acquired in hospitals, including infections with several Gram-negative pathogens that have become increasingly common in hospital settings and are often resistant to multiple antibiotics and hard to treat.

Because the causes of sepsis vary widely and can differ markedly between hospitals, it is difficult to organise conventional clinical treatment trials, which usually involve testing a single treatment against a specific pathogen. Hence, there is very limited evidence to guide clinical decision-making. This is especially problematic as the standard WHO-recommended treatments for bacterial infections in neonates are becoming less effective in many settings, due to antibiotic resistance.

The project

The SNIP-AFRICA project is pioneering a new approach to generate evidence to inform management of sepsis in neonates and young infants in sub-Saharan Africa. It links specialist hospital sites in the region, creating a network through which data can be collected and used in research studies to evaluate the impact of different sepsis treatments.

Within SNIP-AFRICA, a clinical trial called NeoSep1, sponsored by the Global Antibiotic Research and Development Partnership (GARDP), is testing different antibiotic treatments for newborn sepsis at the same time. Instead of focusing on a single drug, the trial compares several treatment options, including combinations of off-patent antibiotics and commonly prescribed antibiotics, such as those recommended by the WHO.

At each hospital, doctors and the trial team select the most relevant treatments to be tested, based on local patterns of infection and antibiotic resistance, as well as the condition of the babies being treated. The aim is to rank these antibiotic options to guide doctors’ clinical decisions across different settings and conditions. The trial will compare options not only in terms of survival, but also side effects, resistance, availability and cost, helping doctors choose the most effective and practical treatments for newborns with sepsis.

A second important component of the SNIP-AFRICA platform is clinical and microbiological surveillance. By embedding data collection for research within routine care, the project will also collate a wealth of additional evidence across different sites, for example, on microbial epidemiology, clinical management, use of healthcare resources, and antibiotic prescribing practices in neonatal units. A real-time data dashboard will be developed to support hospital decision-makers, for example, by showing how local causes of sepsis and resistance patterns are changing. In addition, data collection will provide rapid insights into the impact of changes in clinical practice. 

Pharmacokinetic studies will also be embedded in the platform to explore how circulating drug levels are associated with treatment success. One such study, conducted at South African sites, will improve understanding of how to dose the antibiotic colistin more appropriately in neonates and children under two years of age.

Adaptive platform trials are relatively new and complex to manage. Experience to date suggests that strong governance structures and decision-making rules are needed to ensure clarity on how patients will be treated under different scenarios. The SNIP-AFRICA project will establish a strong but lean governance framework. It will also carry out extensive consultation with health service and community stakeholders to understand their perspectives on adaptive trials and ensure support for research activities embedded within clinical care.

Impact

The SNIP-AFRICA project represents a fundamental shift in how research on the treatment of neonatal sepsis is carried out. It will:

• Establish a multicentre platform able to conduct research and evaluate multiple treatment options for neonatal and infant sepsis.
• Evaluate how well different antibiotic combinations work compared to current global standards and reveal which combinations could help improve the survival of neonates and young infants with sepsis.
• Provide a wealth of additional information for clinicians and hospital managers to optimise local clinical management of sepsis.
• Increase awareness and experience of adaptive platform methodologies across multiple sub-Saharan African countries. 

The SNIP-AFRICA project has the potential to significantly improve the management of sepsis in newborns, generating evidence on potential new treatment options while also demonstrating the power of adaptive trial platforms to simultaneously address multiple knowledge gaps.