Short duration antibiotic therapy for critically ill patients with sepsis (SHORTER trial): a mixed-methods process evaluation of a randomised controlled trial.
Sepsis is a life-threatening organ dysfunction resulting from infection, and a leading global cause of death.1 Timely antibiotic administration is crucial, with guidelines recommending initiation within one hour of recognising severe sepsis.2 Yet, the optimal treatment duration remains uncertain. Antibiotic overuse contributes to the rise of antimicrobial resistance, leading to increased mortality and healthcare costs.3,4 Evidence suggests excessive antibiotic use in critical care settings.5 The SHORTER trial, funded by NIHR Health Technology Assessment (NIHR134101), evaluates short-duration antibiotic therapy's clinical and cost-effectiveness for critically ill sepsis patients.
Methods/Approach
Diverse organisational and participant characteristics, alongside anticipated variations in antibiotic prescribing and de-escalation practices, add to the complexity of successfully delivering this trial. To tackle this complexity, a mixed-methods process evaluation (PE) has been integrated into the trial. The objectives are to 1) assess implementation fidelity, 2) understand clinical staff responses, 3) identify implementation barriers and facilitators, and 4) explore contextual importance. The PE employs a theory-driven approach, integrating the SHORTER intervention logic model, the Conceptual Framework for Implementation Fidelity, and Normalisation Process Theory. All elements of the trial are approved by the Research Ethics Committee (Ref. 23/WA/0197).
Results Structure and Timelines
The trial will span a 43-month period and involve up to 50 UK intensive care units, with an internal pilot conducted during the initial 12 months of recruitment. The PE comprises three phases of data collection – pre, during, and end of trial. Data will be gathered through a combination of questionnaires, semi-structured interviews, observations and routinely collected trial data. Qualitative data will be analysed using a framework approach, enabling synthesis within and across phases. The relationship between SHORTER intervention delivery and trial outcomes will be investigated. Dissemination will be via publications, presentations and media engagement.
Potential Relevance and Impact
Despite large numbers of trials in critical care, few yield positive results, with the process often fraught with challenges.8 Critical care presents unique difficulties for research due to complex ethical and legal requirements, and clinicians having to balance risks and potential benefits.9,10 Despite this, the use of PE in this setting remains low. Enhancing the understanding of factors influencing complex intervention trials in critical care will help to optimise current and future trial delivery. This PE will generate insights into intervention delivery and outcomes, aiding in its application and integration into practice, if successful. It represents a novel approach in critical care research, combining a PE framework with behavioural change theory.
References
1.Shankar-Hari M, Harrison DA, Rubenfeld GD, et al. Epidemiology of sepsis and septic shock in critical care units: comparison between sepsis-2 and sepsis-3 populations using a national critical care database. Br J Anaesth. 2017; 119(4): 626–36.
2.Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021; 49(11): e1063–143.
3.Cassini A, Högberg LD, Plachouras D, et al. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. Lancet Infect Dis. 2019; 19(1): 56–66.
4.Dadgostar P. Antimicrobial Resistance: Implications and Costs. Infect Drug Resist. 2019; 12:3903-3910.
5.Public Health England. English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR): Report 2019 to 2020. Public Health Engl. 2020. www.gov.uk/phe%0Awww.facebook.com/PublicHealthEngland
6.Carroll C, Patterson M, Wood S, et al. conceptual framework for implementation fidelity. Implement Sci. 2007; 2(1): 40.
7.Murray E, Treweek S, Pope C, et al. Normalisation process theory: A framework for developing, evaluating and implementing complex interventions. BMC Medicine. 2010; 8.
8.Laffey JG, Kavanagh BP. Negative trials in critical care: why most research is probably wrong. Lancet Respir Med. 2018; 6(9): 659-660.
9.François B, Clavel M, Vignon P, et al. Perspective on optimising clinical trials in critical care: how to puzzle out recurrent failures. Journal of Intensive Care. 2016; 4(1) :67.
10.Reader TW, Reddy G, Brett SJ. Impossible decision? An investigation of risk trade-offs in the intensive care unit. Ergonomics. 2018; 61(1): 122-133.
Citation
Wojcik, G., Emerson, L., & Hellyer, T. (2024, September). Short duration antibiotic therapy for critically ill patients with sepsis (SHORTER trial): a mixed-methods process evaluation of a randomised controlled trial. Presented at International Clinical Trials Methodology Conference, Edinburgh, UK
Presentation Conference Type
Conference Abstract
Conference Name
International Clinical Trials Methodology Conference
Start Date
Sep 30, 2024
End Date
Oct 3, 2024
Acceptance Date
Aug 15, 2024
Online Publication Date
Sep 30, 2024
Publication Date
2024
Deposit Date
Oct 22, 2024
Peer Reviewed
Peer Reviewed
Pages
388
Book Title
International Clinical Trials Methodology Conference Book of Abstracts
Keywords
Process Evaluation, Clinical Trials, Critical Care, Antibiotic Resistance, Behaviour Change
