Protocol summary and statistical analysis plan for the Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients (SuDDICU) crossover, cluster randomized controlled trial

TY - JOUR

T1 - Protocol summary and statistical analysis plan for the Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients (SuDDICU) crossover, cluster randomized controlled trial

AU - The SuDDICU Investigators

AU - Billot, Laurent

AU - Cuthbertson, Brian

AU - Gordon, Anthony

AU - Al-Beidh, Farah

AU - Correa, Maryam

AU - Davis, Joshua

AU - Finfer, Simon

AU - Glass, Parisa

AU - Goodman, Fiona

AU - Hammond, Naomi

AU - Iredell, Jonathon

AU - Miller, Jennene

AU - Murthy, Srinivas

AU - Rose, Louise

AU - Seppelt, Ian

AU - Taylor, Colman

AU - Young, Paul

AU - Myburgh, John

N1 - Funding Information: The study is funded by the National Health and Medical Research Council (NHMRC) of Australia (Project Grant 1084244) and the Canadian Institutes of Health Research (Strategy for Patient Orientated Research Project Grant 381434 and Project Grant 378431). These agencies had no input into the study design, and will have no input into study conduct, data analysis, or presentation and publication of the trial results. Funding Information: Acknowledgements: Anthony Gordon is funded by a National Institute for Health Research Professorship and is supported by the NIHR Imperial Biomedical Research Centre; Joshua Davis is supported by an NHMRC Career Development Fellowship; Simon Finfer is supported by an NHMRC Practitioner Fellowship; Naomi Hammond is supported by an NHMRC Investigator Grant; Jonathon Iredell is supported by an NHMRC Practitioner Fellowship; Srinivas Murthy is funded by a Health Research Foundation and Innovative Medicines Canada Research Chair program; John Myburgh is supported by an NHMRC Leadership Fellowship. This article is endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group. Funding Information: Anthony Gordon is funded by a National Institute for Health Research Professorship and is supported by the NIHR Imperial Biomedical Research Centre; Joshua Davis is supported by an NHMRC Career Development Fellowship; Simon Finfer is supported by an NHMRC Practitioner Fellowship; Naomi Hammond is supported by an NHMRC Investigator Grant; Jonathon Iredell is supported by an NHMRC Practitioner Fellowship; Srinivas Murthy is funded by a Health Research Foundation and Innovative Medicines Canada Research Chair program; John Myburgh is supported by an NHMRC Leadership Fellowship. This article is endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group. Funding Information: Two pre-specified, independently funded substudies will run concurrently with the SuDDICU x-cRCT. First, an ecological substudy will be conducted in selected Australian ICUs to determine rates of colonisation by antibiotic-resistant organisms in patients treated with SDD and non-SDD antibiotics. This will involve characterisation of microflora and microbiome genomics, metagenomic changes over time, and associations between these changes and clinical outcomes. This substudy is funded by the NHMRC (Project Grant APP1127292). Second, a process evaluation exploring context and process of trial implementation will be conducted in Canadian and UK ICUs. This substudy is funded by the Canadian Institutes of Health Research (Grant 171478). Publisher Copyright: © 2021, College of Intensive Care Medicine. All rights reserved.

PY - 2021/6

Y1 - 2021/6

N2 - Background: It is unclear whether the use of selective decontamination of the digestive tract (SDD) improves outcomes in ventilated patients in intensive care units (ICUs) and whether SDD is associated with the development of antibiotic resistance. Objective: To describe the study protocol and statistical analysis plan for the Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients (SuDDICU) trial. Design, setting, participants and intervention: SuDDICU is an international, crossover, cluster randomised controlled trial of mechanically ventilated patients in ICUs using two 12-month trial periods. For each period, participating ICUs will implement SDD plus standard care or standard care alone. The SuDDICU drug intervention is an oral paste and gastric suspension of three antibiotics combined with a 4-day course of intravenous antibiotics. Observational ecological assessments will be conducted during five surveillance periods. The trial will be conducted in 19 ICUs in Australia and ten ICUs in Canada and the United Kingdom, and will recruit 15 000–17 000 patients. Recruitment commenced in Australia in 2017. Main outcome measures: The primary outcome is all-cause hospital mortality. Secondary outcomes include: Duration of ventilation, ICU stay and hospital stay; incidence of new antibiotic-resistant organisms during the index ICU admission; changes in antibiotic-resistant organism rates; incidence of new Clostridioides difficile infections; and total use of antibiotics. Results and conclusions: SuDDICU will determine whether the use of SDD plus standard care is associated with a reduction in hospital mortality in ventilated ICU patients compared with standard care alone. It will also quantify the impact of the use of SDD on the development of antibiotic resistance. Trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12615000411549) and ClinicalTrials.gov (NCT02389036).established through critical care clinical trial networks in Australia, New Zealand, Canada and the United Kingdom in 2009. The aim of this international collaboration is to design and conduct an integrated research program to address this fundamental knowledge and implementation gap that has concerned intensive care clinicians for more than 40 years. The program commenced with the publication of systematic reviews about the effects of SDD on mortality and antibiotic resistance,16,17 descriptive studies of barriers to global implementation of SDD,18,19 and feasibility studies.20 These initiatives informed the design of a large scale RCT aimed at determining whether SDD improves patient-centred outcomes without the development of antibiotic resistance. In this article, we describe the study protocol and statistical analysis plan for the Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients (SuDDICU) crossover, cluster RCT.

AB - Background: It is unclear whether the use of selective decontamination of the digestive tract (SDD) improves outcomes in ventilated patients in intensive care units (ICUs) and whether SDD is associated with the development of antibiotic resistance. Objective: To describe the study protocol and statistical analysis plan for the Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients (SuDDICU) trial. Design, setting, participants and intervention: SuDDICU is an international, crossover, cluster randomised controlled trial of mechanically ventilated patients in ICUs using two 12-month trial periods. For each period, participating ICUs will implement SDD plus standard care or standard care alone. The SuDDICU drug intervention is an oral paste and gastric suspension of three antibiotics combined with a 4-day course of intravenous antibiotics. Observational ecological assessments will be conducted during five surveillance periods. The trial will be conducted in 19 ICUs in Australia and ten ICUs in Canada and the United Kingdom, and will recruit 15 000–17 000 patients. Recruitment commenced in Australia in 2017. Main outcome measures: The primary outcome is all-cause hospital mortality. Secondary outcomes include: Duration of ventilation, ICU stay and hospital stay; incidence of new antibiotic-resistant organisms during the index ICU admission; changes in antibiotic-resistant organism rates; incidence of new Clostridioides difficile infections; and total use of antibiotics. Results and conclusions: SuDDICU will determine whether the use of SDD plus standard care is associated with a reduction in hospital mortality in ventilated ICU patients compared with standard care alone. It will also quantify the impact of the use of SDD on the development of antibiotic resistance. Trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12615000411549) and ClinicalTrials.gov (NCT02389036).established through critical care clinical trial networks in Australia, New Zealand, Canada and the United Kingdom in 2009. The aim of this international collaboration is to design and conduct an integrated research program to address this fundamental knowledge and implementation gap that has concerned intensive care clinicians for more than 40 years. The program commenced with the publication of systematic reviews about the effects of SDD on mortality and antibiotic resistance,16,17 descriptive studies of barriers to global implementation of SDD,18,19 and feasibility studies.20 These initiatives informed the design of a large scale RCT aimed at determining whether SDD improves patient-centred outcomes without the development of antibiotic resistance. In this article, we describe the study protocol and statistical analysis plan for the Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients (SuDDICU) crossover, cluster RCT.

UR - http://www.scopus.com/inward/record.url?scp=85127113723&partnerID=8YFLogxK

U2 - 10.51893/2021.2.oa5

DO - 10.51893/2021.2.oa5

M3 - Article

AN - SCOPUS:85127113723

SN - 1441-2772

VL - 23

SP - 183

EP - 193

JO - Critical Care and Resuscitation

JF - Critical Care and Resuscitation

IS - 2

ER -