biomArker-guided Duration of Antibiotic treatment in hospitalised Patients with suspecTed Sepsis (ADAPT-Sepsis): A protocol for a multicentre randomised controlled trial

Paul Dark; Gavin D Perkins; Ronan McMullan; Danny McAuley; Anthony C Gordon; Jonathan Clayton; Dipesh Mistry; Keith Young; Scott Regan; Nicola McGowan; Matt Stevenson; Simon Gates; Gordon L Carlson; Tim Walsh; Nazir I Lone; Paul R Mouncey; Mervyn Singer; Peter Wilson; Tim Felton; Kay Marshall; Anower M Hossain; Ranjit Lall

doi:10.1177/17511437231169193

biomArker-guided Duration of Antibiotic treatment in hospitalised Patients with suspecTed Sepsis (ADAPT-Sepsis): A protocol for a multicentre randomised controlled trial

J Intensive Care Soc. 2023 Nov;24(4):427-434. doi: 10.1177/17511437231169193. Epub 2023 Apr 25.

Authors

Paul Dark¹, Gavin D Perkins², Ronan McMullan³, Danny McAuley³, Anthony C Gordon⁴, Jonathan Clayton⁵, Dipesh Mistry², Keith Young², Scott Regan², Nicola McGowan², Matt Stevenson⁶, Simon Gates⁷, Gordon L Carlson⁸, Tim Walsh⁹, Nazir I Lone⁹, Paul R Mouncey¹⁰, Mervyn Singer¹¹, Peter Wilson¹², Tim Felton¹³, Kay Marshall¹⁴, Anower M Hossain², Ranjit Lall²

Affiliations

¹ Division of Immunology, Immunity to Infection and Respiratory Medicine, University of Manchester, Critical Care Unit, Northern Care Alliance NHS Foundation Trust, Salford Care Organisation, Greater Manchester, UK.
² Warwick Medical School, Clinical Trials Unit, University of Warwick, Coventry, UK.
³ Wellcome Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast, UK.
⁴ Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, UK.
⁵ Clinical Biochemistry Department, Lancashire Teaching Hospitals NHS Foundation Trust, Sharoe Green Lane, Fulwood, Preston Lancashire, UK.
⁶ School of Health and Related Research, The University of Sheffield Western Bank, Sheffield, UK.
⁷ Cancer Research Clinical Trials Unit, Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
⁸ National Intestinal Failure Centre, Northern Care Alliance NHS Foundation Trust, Salford Care Organisation, Greater Manchester, UK.
⁹ Anaesthesia, Critical Care and Pain Medicine, Usher Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh Royal Infirmary, Edinburgh, UK.
¹⁰ Clinical Trials Unit, Intensive Care National Audit and Research Centre, Napier House, London, UK.
¹¹ Centre for Intensive Care Medicine, Experimental and Translational Medicine, Division of Medicine, Faculty of Medical Sciences, University College London, London, UK.
¹² Clinical Microbiology, University College London Hospitals NHS Foundation Trust, London, UK.
¹³ Respiratory Academic Group, Division of Immunology, Immunity to Infection and Respiratory Medicine, University of Manchester, Wythenshawe Hospital, Manchester, UK.
¹⁴ Pharmacy and Pharmaceutical Sciences, School of Health Sciences, University of Manchester, Manchester, UK.

Abstract

Aim: To describe the protocol for a multi-centre randomised controlled trial to determine whether treatment protocols monitoring daily CRP (C-reactive protein) or PCT (procalcitonin) safely allow a reduction in duration of antibiotic therapy in hospitalised adult patients with sepsis.

Design: Multicentre three-arm randomised controlled trial.

Setting: UK NHS hospitals.

Target population: Hospitalised critically ill adults who have been commenced on intravenous antibiotics for sepsis.

Health technology: Three protocols for guiding antibiotic discontinuation will be compared: (a) standard care; (b) standard care + daily CRP monitoring; (c) standard care + daily PCT monitoring. Standard care will be based on routine sepsis management and antibiotic stewardship. Measurement of outcomes and costs. Outcomes will be assessed to 28 days. The primary outcomes are total duration of antibiotics and safety outcome of all-cause mortality. Secondary outcomes include: escalation of care/re-admission; infection re-lapse/recurrence; antibiotic dose; length and level of critical care stay and length of hospital stay. Ninety-day all-cause mortality rates will also be collected. An assessment of cost effectiveness will be performed.

Conclusion: In the setting of routine NHS care, if this trial finds that a treatment protocol based on monitoring CRP or PCT safely allows a reduction in duration of antibiotic therapy, and is cost effective, then this has the potential to change clinical practice for critically ill patients with sepsis. Moreover, if a biomarker-guided protocol is not found to be effective, then it will be important to avoid its use in sepsis and prevent ineffective technology becoming widely adopted in clinical practice.

Keywords: Antibiotic duration; C-reactive protein; biomarkers; procalcitonin; sepsis.