PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal use of antibiotics in the emergency department (PRONTO): protocol for a multicentre, open-label, randomised controlled trial
Introduction Sepsis is a common, potentially life-threatening complication of infection. The optimal treatment for sepsis includes prompt antibiotics and intravenous fluids, facilitated by its early and accurate recognition. Currently, clinicians identify and assess severity of suspected sepsis usin...
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2022-06-01
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| author | David Taylor-Robinson Steve Goodacre Neil French Richard Body Kerenza Hood Emma Thomas-Jones Jane Daniels Sarah Walker Ingeborg Welters Mike Bradburn Paul Schmidt Enitan Carrol Lucy Brookes-Howell Sarah Milosevic Andrew Tabner Philip Pallmann Stephen Aston Gavin Barlow Emma Richards Emmanuel Nsutebu Philip Howard Matthew Inada-Kim Stacy Todd Fiona McGill Martin Llewelyn Louis Wihelmus Niessen Joanne Euden Julie Carman Stephanie Gilbert Sam Clarkstone Jacqui Hughes Lena Meister Angela Brain Matthew Scarborough Sian O'Shea Claire James |
| author_facet | David Taylor-Robinson Steve Goodacre Neil French Richard Body Kerenza Hood Emma Thomas-Jones Jane Daniels Sarah Walker Ingeborg Welters Mike Bradburn Paul Schmidt Enitan Carrol Lucy Brookes-Howell Sarah Milosevic Andrew Tabner Philip Pallmann Stephen Aston Gavin Barlow Emma Richards Emmanuel Nsutebu Philip Howard Matthew Inada-Kim Stacy Todd Fiona McGill Martin Llewelyn Louis Wihelmus Niessen Joanne Euden Julie Carman Stephanie Gilbert Sam Clarkstone Jacqui Hughes Lena Meister Angela Brain Matthew Scarborough Sian O'Shea Claire James |
| collection | DOAJ |
| description | Introduction Sepsis is a common, potentially life-threatening complication of infection. The optimal treatment for sepsis includes prompt antibiotics and intravenous fluids, facilitated by its early and accurate recognition. Currently, clinicians identify and assess severity of suspected sepsis using validated clinical scoring systems. In England, the National Early Warning Score 2 (NEWS2) has been mandated across all National Health Service (NHS) trusts and ambulance organisations. Like many clinical scoring systems, NEWS2 should not be used without clinical judgement to determine either the level of acuity or a diagnosis. Despite this, there is a tendency to overemphasise the score in isolation in patients with suspected infection, leading to the overprescription of antibiotics and potentially treatment-related complications and rising antimicrobial resistance. The biomarker procalcitonin (PCT) has been shown to be useful in specific circumstances to support appropriate antibiotics prescribing by identifying bacterial infection. PCT is not routinely used in the care of undifferentiated patients presenting to emergency departments (EDs), and the evidence base of its optimal usage is poor. The PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal (PRONTO) study is a randomised controlled trial (RCT) in adults with suspected sepsis presenting to the ED to compare standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment with standard clinical management based on NEWS2 scoring alone and compare if this approach reduces prescriptions of antibiotics without increasing mortality.Methods and analysis PRONTO is a parallel two-arm open-label individually RCT set in up to 20 NHS EDs in the UK with a target sample size of 7676 participants. Participants will be randomised in a ratio of 1:1 to standard clinical management based on NEWS2 scoring or standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment. We will compare whether the addition of PCT measurement to NEWS2 scoring can lead to a reduction in intravenous antibiotic initiation in ED patients managed as suspected sepsis, with at least no increase in 28-day mortality compared with NEWS2 scoring alone (in conjunction with local standard care pathways). PRONTO has two coprimary endpoints: initiation of intravenous antibiotics at 3 hours (superiority comparison) and 28-day mortality (non-inferiority comparison). The study has an internal pilot phase and group-sequential stopping rules for effectiveness and futility/safety, as well as a qualitative substudy and a health economic evaluation.Ethics and dissemination The trial protocol was approved by the Health Research Authority (HRA) and NHS Research Ethics Committee (Wales REC 2, reference 20/WA/0058). In England and Wales, the law allows the use of deferred consent in approved research situations (including ED studies) where the time dependent nature of intervention would not allow true informed consent to be obtained. PRONTO has approval for a deferred consent process to be used. Findings will be disseminated through peer-reviewed journals and presented at scientific conferences.Trial registration number ISRCTN54006056. |
| format | Article |
| id | doaj-art-06a8ecad423d4fceb4fae3c4acfa0355 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2022-06-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-06a8ecad423d4fceb4fae3c4acfa03552025-01-24T05:20:09ZengBMJ Publishing GroupBMJ Open2044-60552022-06-0112610.1136/bmjopen-2022-063424PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal use of antibiotics in the emergency department (PRONTO): protocol for a multicentre, open-label, randomised controlled trial David Taylor-Robinson0Steve Goodacre1Neil French2Richard Body3Kerenza Hood4Emma Thomas-Jones5Jane Daniels6Sarah Walker7Ingeborg Welters8Mike Bradburn9Paul Schmidt10Enitan Carrol11Lucy Brookes-Howell12Sarah Milosevic13Andrew Tabner14Philip Pallmann15Stephen Aston16Gavin BarlowEmma Richards17Emmanuel Nsutebu18Philip Howard19Matthew Inada-Kim20Stacy Todd21Fiona McGill22Martin Llewelyn23Louis Wihelmus Niessen24Joanne Euden25Julie Carman26Stephanie Gilbert27Sam ClarkstoneJacqui HughesLena MeisterAngela BrainMatthew ScarboroughSian O'SheaClaire James1 Department of Public Health, Policy and Systems, University of Liverpool, Liverpool, UKThe University of Sheffield, Sheffield Centre for Health and Related Research (SCHARR), Sheffield, UKprofessor in infectious diseasesDivision of Cardiovascular Sciences, The University of Manchester, Manchester, UKCardiff University College of Biomedical and Life Sciences, Cardiff, UKCentre for Trials Research, Cardiff University College of Biomedical and Life Sciences, Cardiff, UKNottingham Clinical Trials Unit, School of Medicine, University of Nottingham Faculty of Medicine and Health Sciences, Nottingham, Nottingham, UK3 University of Exeter Medical School, Exeter, UKInstitute of Life Course and Medical Science, University of Liverpool, Liverpool, UKSchool of Health and Related Research (ScHARR), The University of Sheffield, Sheffield, UKAcute Medical Unit, Portsmouth Hospitals NHS Trust, Portsmouth, UKInstitute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UKCentre for Trials Research, Cardiff University, Cardiff, UKCentre for Trials Research, Cardiff University, Cardiff, UKSchool of Medicine, University of Nottingham, Medical School, Nottingham, UK1 Centre for Trials Research, Cardiff University College of Biomedical and Life Sciences, Cardiff, UK3 Tropical and Infectious Diseases Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UKENT, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UKinfectious disease physicianSchool of Healthcare, University of Leeds, Leeds, UKDepartment of Acute Medicine, Hampshire Hospitals NHS Foundation Trust, Winchester, UKDepartment of Respiratory Medicine, Tropical and Infectious Disease Unit, Intensive care Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UKInstitute of Infection, Veterinary and Ecological sciences, University of Liverpool, Liverpool, Merseyside, UKDepartment of Microbiology and Infection, University Hospitals Sussex NHS Foundation Trust, Brighton, UKDepartment of International Public Health, Liverpool School of Tropical Medicine, Liverpool, UKCentre for Trials Research, Cardiff University College of Biomedical and Life Sciences, Cardiff, UK2Bristol-Myers Squibb, New Jersey, United States of AmericaCentre for Trials Research, Cardiff University, Cardiff, UKIntroduction Sepsis is a common, potentially life-threatening complication of infection. The optimal treatment for sepsis includes prompt antibiotics and intravenous fluids, facilitated by its early and accurate recognition. Currently, clinicians identify and assess severity of suspected sepsis using validated clinical scoring systems. In England, the National Early Warning Score 2 (NEWS2) has been mandated across all National Health Service (NHS) trusts and ambulance organisations. Like many clinical scoring systems, NEWS2 should not be used without clinical judgement to determine either the level of acuity or a diagnosis. Despite this, there is a tendency to overemphasise the score in isolation in patients with suspected infection, leading to the overprescription of antibiotics and potentially treatment-related complications and rising antimicrobial resistance. The biomarker procalcitonin (PCT) has been shown to be useful in specific circumstances to support appropriate antibiotics prescribing by identifying bacterial infection. PCT is not routinely used in the care of undifferentiated patients presenting to emergency departments (EDs), and the evidence base of its optimal usage is poor. The PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal (PRONTO) study is a randomised controlled trial (RCT) in adults with suspected sepsis presenting to the ED to compare standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment with standard clinical management based on NEWS2 scoring alone and compare if this approach reduces prescriptions of antibiotics without increasing mortality.Methods and analysis PRONTO is a parallel two-arm open-label individually RCT set in up to 20 NHS EDs in the UK with a target sample size of 7676 participants. Participants will be randomised in a ratio of 1:1 to standard clinical management based on NEWS2 scoring or standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment. We will compare whether the addition of PCT measurement to NEWS2 scoring can lead to a reduction in intravenous antibiotic initiation in ED patients managed as suspected sepsis, with at least no increase in 28-day mortality compared with NEWS2 scoring alone (in conjunction with local standard care pathways). PRONTO has two coprimary endpoints: initiation of intravenous antibiotics at 3 hours (superiority comparison) and 28-day mortality (non-inferiority comparison). The study has an internal pilot phase and group-sequential stopping rules for effectiveness and futility/safety, as well as a qualitative substudy and a health economic evaluation.Ethics and dissemination The trial protocol was approved by the Health Research Authority (HRA) and NHS Research Ethics Committee (Wales REC 2, reference 20/WA/0058). In England and Wales, the law allows the use of deferred consent in approved research situations (including ED studies) where the time dependent nature of intervention would not allow true informed consent to be obtained. PRONTO has approval for a deferred consent process to be used. Findings will be disseminated through peer-reviewed journals and presented at scientific conferences.Trial registration number ISRCTN54006056.https://bmjopen.bmj.com/content/12/6/e063424.full |
| spellingShingle | David Taylor-Robinson Steve Goodacre Neil French Richard Body Kerenza Hood Emma Thomas-Jones Jane Daniels Sarah Walker Ingeborg Welters Mike Bradburn Paul Schmidt Enitan Carrol Lucy Brookes-Howell Sarah Milosevic Andrew Tabner Philip Pallmann Stephen Aston Gavin Barlow Emma Richards Emmanuel Nsutebu Philip Howard Matthew Inada-Kim Stacy Todd Fiona McGill Martin Llewelyn Louis Wihelmus Niessen Joanne Euden Julie Carman Stephanie Gilbert Sam Clarkstone Jacqui Hughes Lena Meister Angela Brain Matthew Scarborough Sian O'Shea Claire James PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal use of antibiotics in the emergency department (PRONTO): protocol for a multicentre, open-label, randomised controlled trial BMJ Open |
| title | PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal use of antibiotics in the emergency department (PRONTO): protocol for a multicentre, open-label, randomised controlled trial |
| title_full | PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal use of antibiotics in the emergency department (PRONTO): protocol for a multicentre, open-label, randomised controlled trial |
| title_fullStr | PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal use of antibiotics in the emergency department (PRONTO): protocol for a multicentre, open-label, randomised controlled trial |
| title_full_unstemmed | PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal use of antibiotics in the emergency department (PRONTO): protocol for a multicentre, open-label, randomised controlled trial |
| title_short | PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal use of antibiotics in the emergency department (PRONTO): protocol for a multicentre, open-label, randomised controlled trial |
| title_sort | procalcitonin and news2 evaluation for timely identification of sepsis and optimal use of antibiotics in the emergency department pronto protocol for a multicentre open label randomised controlled trial |
| url | https://bmjopen.bmj.com/content/12/6/e063424.full |
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