Information for the Public

UPDATE TO PRIVACY NOTICE

The personal identifiers, NHS Number and Date of Birth, will be shared with NHS England for the purposes of linkage and extraction of outcomes data, and
If the study participant is not happy with this, they can apply to withdraw from the study.
https://www.manchester.ac.uk/discover/privacy-information/data-protection/privacy-notices/

Latest news

The ADAPT Sepsis trial paper has recently been published in JAMA

Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected SepsisThe ADAPT-Sepsis Randomized Clinical Trial

Paul Dark, MD, PhD¹Link opens in a new windowLink opens in a new windowLink opens in a new window; Anower Hossain, PhD²Link opens in a new windowLink opens in a new windowLink opens in a new window; Daniel F. McAuley, MD^3,11Link opens in a new windowLink opens in a new windowLink opens in a new window; et al
https://jamanetwork.com/journals/jama/fullarticle/2828036

Lay Summary of study results

Final Report

Background

Sepsis is a common life-threatening condition that is triggered by infection. In sepsis, the body’s defence mechanisms (immune system) react excessively, resulting in widespread inflammation and swelling. If not treated quickly, sepsis can result in the shutdown of vital organs which can result in death. Each year in the UK, more than 100,000 people are admitted to hospital with sepsis and around 37,000 will die. Earlier research indicates that early recognition of sepsis and rapid antibiotic treatments are the most crucial factors for patient survival. Many patients with sepsis are treated in intensive care units in hospitals where they be provided with high levels of skilled clinical care.

The human body naturally has certain organic compounds that can be measured in laboratories. The level of some of these compounds – called biomarkers – change when there is an infection. The levels of two in particular - called procalcitonin (PCT) and C-Reactive protein (CRP) - are raised when a person has sepsis. As a patient recovers from sepsis, these elevated levels fall.

The normal, or standard, treatment of sepsis is a course of powerful antibiotics lasting seven days or more. Whilst this is normally successful, it is not without risk to the patient and excessive or unnecessary use of antibiotics can lead to the increased risk of antibiotic resistance. Antibiotic resistance can make the treatment of other infections more difficult. A trial was therefore developed that explored whether the regular measuring of the PCT and CRP biomarkers could lead to the reduced use of antibiotics and improved outcomes for patients.

The Trial

The Trial was designed to determine whether the regular monitoring of PCT or CRP compared with standard care in critically ill patients with sepsis could lead to reduced antibiotic use without compromising patient safety or outcomes.

The Trail was conducted in a total of 41 hospitals between January 2018 and July 2024. It was paused between March 2020 and August 2020 during the COVID-19 pandemic. Not all the hospitals that were taking part before this closure rejoined afterwards but new ones were subsequently recruited. These hospitals ranged in size from relatively small district general hospitals to large, multi-specialist teaching centres and were located throughout the United Kingdom.

A total of 2760 patients were recruited to the trial randomly allocated to one of three trial arms –one for the measuring PCT levels (a total of 918 patients), one measured CRP levels (a total of 924 patients) and one provided standard care (a total of 918 patients). All the patients were over 18 years of age, likely to still be in hospital and receiving antibiotics intravenously for at least 72 hours and had been identified within 24 hours of first receiving antibiotic treatment. Each patient was randomly allocated to one of the arms by an automated computer system run through the Warwick University Clinical Trials Unit (Warwick CTU). The primary aim of the Trial was to assess the use of antibiotics up to 28 days from the day that the patient enrolled in the Trial. Patients were, however, continued to be monitored for up to 90 days so that clinical outcomes could be monitored and compared.

Methods

The Trial required that a sample of blood be taken daily from each participant and sent to the local NHS quality assured biomarker testing laboratory. For those patients in the PCT and CRP arms, known as the ‘intervention arms,’ the sample was tested, and these results were entered into a database hosted at the Warwick CTU. Samples from those in the standard care arm were not tested for biomarkers but were still tested for other relevant conditions such as white blood cell count. In all cases, the clinicians treating the patients received standardised reports that, in the case of the intervention arms, recommended continuing or discontinuing the use of antibiotics. The guidance was informed by the reported levels of the biomarker. In the case of those in the standard care arm, the recommendation was for a continuation of standard care. The treating clinician was not, however, aware of the particular arm that the patient was in.

Results

Compared with the standard care, there was a consistent average reduction in the use of antibiotics in those patients whose levels of PCT were monitored but no significant reduction was identified for those whose CRP levels were monitored. This reduction amounted to an average of 1 day of antibiotics per patient for an average of 10 days of antibiotics used for sepsis up to 28 days. Although this 10% saving in antibiotics may seem a modest reduction, considering the number of critically ill patients with sepsis that are treated each year across the UK, the reduction equates to a meaningful reduction in the use of antibiotics in patients with sepsis.

In terms of patient safety, there were no detectable differences in patient morbidity or mortality at either 28 or 90 days between any of the three arms.

This report focusses on the clinical aspects of the Trial. A further report is to be prepared in due course that considers health economics and procedural aspects.

Conclusion

Sepsis patient care guided by measurement of PCT reduces antibiotic duration safely compared with standard care, but CRP does not.