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Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients (SuDDICU)

Primary Purpose

Critical Illness, Sepsis, Septic Shock

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
SDD Oral Paste
SDD Gastric Suspension
Intravenous Antibiotic
Sponsored by
The George Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Critical Illness

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Site inclusion for cluster study- A general ICU or complex of ICUs (medical, surgical, mixed) capable of treating mechanically ventilated critically ill adult patients.

Patient inclusion criteria

  1. All patients who are mechanically ventilated via an endotracheal tube on admission to ICU and who are predicted to remain ventilated beyond the end of the calendar day after the day of ICU admission, or
  2. All patients who become mechanically ventilated via an endotracheal tube during their ICU stay and who are predicted to remain ventilated beyond the end of the calendar day after the day they are first ventilated, or
  3. All patients not already recruited who are receiving mechanical ventilation via an endotracheal tube and are expected to receive ongoing ventilation for a further 48 hours or more despite an earlier prediction that ventilation would be discontinued earlier.

Site exclusion criteria for cluster study-

  1. Unwilling or unable to follow trial protocols.
  2. Unable to capture the minimum data set required for the study.
  3. Isolated specialty ICUs not co-located with a general ICU, such as solely cardiac, neurological/neurosurgical and burns ICUs, but such specialty patients cared for in general ICUs will be included
  4. Specialty paediatric ICUs

Exclusion Criteria:

Patient exclusion criteria

  1. Patients enrolled in a trial that would interact with the intervention
  2. Patients with a known allergy, sensitivity or interaction to trial topical intervention drugs
  3. Patients who are known or suspected to be pregnant
  4. Patients who are moribund and not expected to survive the next 12 hours
  5. Patients less than 16 years of age will not be enrolled in the UK

Sites / Locations

  • The George Institute for Global Health
  • Sunnybrook Health Sciences Centre
  • Imperial College London

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Control group- standard care

SDD intervention group

Arm Description

Standard care- In Australia there are no national guidelines so local policy is determined by each ICU. We are recommending (but not mandating) that control and SDD group management be in line with these national guidelines. We will recommend control and SDD group management is in line with current national standards of practice that may or may not include a VAP bundle. We will monitor record data regarding the nature and delivery of the control and SDD group co-interventions.

The intervention will entail: A six-hourly topical application of 0.5g paste, containing colistin 10mg, tobramycin 10mg and nystatin 125,000 IU, to the buccal mucosa and oropharynx A six-hourly administration of 10 mL of a suspension containing 100 mg colistin, 80 mg tobramycin and 2 x 10^6 IU nystatin, to the gastrointestinal tract via a gastric/post-pyloric tube A four-day course of an IV antibiotic. Patients not already receiving a therapeutic antibiotic will be prescribed cefotaxime 1g six-hourly or ceftriaxone 1g daily, with dose adjusted as appropriate for organ dysfunction. Ciprofloxacin (400mg 12-hourly) may be used as an alternative if there is a contraindication to cephalosporins (e.g. allergy). Patients already receiving an alternative IV antibiotic to treat infection will not receive this additional IV antibiotic, but will continue the prescribed antibiotic for the usual duration of therapy.

Outcomes

Primary Outcome Measures

Hospital Mortality
all-cause mortality at time of hospital discharge

Secondary Outcome Measures

Total antibiotic usage
Total antibiotic usage (as daily defined doses) during ICU admission in all ICU admissions.
The incidence of antibiotic resistant organisms in cultures from blood or other sterile sites
The incidence of antibiotic resistant organisms in cultures from blood or other sterile sites during ICU admission in all ICU admissions.
The incidence of antibiotic-resistant organism in non-sterile clinical and surveillance specimens
The incidence of antibiotic-resistant organism in non-sterile clinical and surveillance specimens during ICU admission in all ICU admissions
The incidence of C. difficile infections
The incidence of C. difficile infections during ICU admission in all ICU admissions
Changes in antibiotic resistance rates between study epochs (pre-trial, interperiod gap and post-trial) within groups
Changes in ARO rates between time epochs (pre-trial, trial, inter-period gap and post-trial) within groups. With control group data to give the secular trend in ARO with time and SDD group data studying the effects of SDD withdrawal from practice in the year after SDD delivery
Duration of mechanical ventilation
Duration that the patient is mechanically ventilated in the ICU
ICU length of stay
The length of time a patient stays in the ICU
Hospital length of stay
The total hospital length of stay for patient
ICU Mortality
mortality at time of ICU discharge

Full Information

First Posted
March 2, 2015
Last Updated
August 9, 2023
Sponsor
The George Institute
Collaborators
Imperial College London, Sunnybrook Health Sciences Centre
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1. Study Identification

Unique Protocol Identification Number
NCT02389036
Brief Title
Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients
Acronym
SuDDICU
Official Title
A Crossover, Cluster Randomised Controlled Trial of Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients (SuDDICU)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
May 1, 2017 (Actual)
Primary Completion Date
April 26, 2023 (Actual)
Study Completion Date
April 26, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The George Institute
Collaborators
Imperial College London, Sunnybrook Health Sciences Centre

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Introduction- Hospital acquired infections (HAI) are a major cause of morbidity and mortality and increase health care costs. Critically ill patients are particularly susceptible to these infections and have an even higher mortality. One intervention that has gained much interest in the medical literature for reducing infection rates and deaths from HAIs is selective decontamination of the digestive tract (SDD). SDD involves the application of antibiotic paste to the mouth, throat, stomach and a short course of intravenous antibiotics. The evidence supporting the use of SDD for saving lives and preventing infections is actually quite strong. However, health care professionals in many parts of the world have refrained from using SDD due to fears of the effects of overuse of antibiotics on the frequency of infections with resistant bacteria such as multi-resistant Gram negative organisms, MRSA and Clostridium difficile. SuDDICU is a cross-over, cluster randomised trial comparing the effect of using selective decontamination of the digestive tract (SDD) plus standard care, to standard care alone on hospital mortality in patients receiving mechanical ventilation in the intensive care unit (ICU). Secondary outcomes include an ecological assessment and a long-term health economic analysis.
Detailed Description
Design- international, multicentre, crossover, cluster randomised controlled trial (x-cRCT) of eligible patients in participating ICUs using two 12-month interventional trial periods separated by a 3-month inter-period gap. An observational ecological assessment will be conducted in all ICU patients during one week of each month during the 3-month surveillance period before the first intervention period; in all trial eligible patients during the two 12-month intervention periods; in all ICU patients during one week of each month of the final 3-months of the two intervention periods; in all ICU patients during one week of each month during the 3-month inter-period and post-trial periods. Participants- General ICUs that admit mechanically ventilated patients will be randomised in the first 12-month period to either implement the SDD protocol in addition to standard care or to continue standard care without SDD, and then to cross over to the other arm during the second 12-month period. Eligible patients are defined as: All patients who are mechanically ventilated via an endotracheal tube on admission to the ICU and who are predicted to remain ventilated beyond the end of the calendar day after the day of ICU admission, or All patients who become mechanically ventilated via an endotracheal tube during their ICU stay and who are predicted to remain ventilated beyond the end of the calendar day after the day they are first ventilated, or All patients who not already recruited but are receiving mechanical ventilation via an endotracheal tube and are expected to receive ongoing ventilation for a further 48-hours or more despite an earlier prediction that ventilation would be discontinued earlier. All patients eligible for the intervention will receive the following in addition to the usual infection control measures: 1. A six-hourly topical application of 0.5g paste, containing colistin 10mg, tobramycin 10mg and nystatin 125,000 IU, to the buccal mucosa and oropharynx A six-hourly administration of 10 mL of a suspension containing 100 mg colistin, 80 mg tobramycin and 2 x 106 IU nystatin, to the gastrointestinal tract via a gastric/post-pyloric tube A four-day course of an IV antibiotic. Patients not already receiving a therapeutic antibiotic will be prescribed cefotaxime 1g six-hourly or ceftriaxone 1g daily, with dose adjusted as appropriate for organ dysfunction. Ciprofloxacin (400mg 12-hourly) may be used as an alternative if there is a contraindication to cephalosporins (e.g. allergy). Patients already receiving an alternative IV antibiotic to treat infection will not receive this additional IV antibiotic, but will continue the prescribed antibiotic for the usual duration of therapy. Statistical considerations and sample size- SuDDICU will recruit 10 000 to 15 000 patients from 29 ICUs and will have 80% power to detect an absolute reduction in hospital mortality of 3-5% from a baseline mortality of 29%, depending on the precise number of clusters.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Critical Illness, Sepsis, Septic Shock, Ventilator Associated Pneumonia

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Model Description
Cluster, crossover, randomized clinical trial
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
20010 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Control group- standard care
Arm Type
No Intervention
Arm Description
Standard care- In Australia there are no national guidelines so local policy is determined by each ICU. We are recommending (but not mandating) that control and SDD group management be in line with these national guidelines. We will recommend control and SDD group management is in line with current national standards of practice that may or may not include a VAP bundle. We will monitor record data regarding the nature and delivery of the control and SDD group co-interventions.
Arm Title
SDD intervention group
Arm Type
Experimental
Arm Description
The intervention will entail: A six-hourly topical application of 0.5g paste, containing colistin 10mg, tobramycin 10mg and nystatin 125,000 IU, to the buccal mucosa and oropharynx A six-hourly administration of 10 mL of a suspension containing 100 mg colistin, 80 mg tobramycin and 2 x 10^6 IU nystatin, to the gastrointestinal tract via a gastric/post-pyloric tube A four-day course of an IV antibiotic. Patients not already receiving a therapeutic antibiotic will be prescribed cefotaxime 1g six-hourly or ceftriaxone 1g daily, with dose adjusted as appropriate for organ dysfunction. Ciprofloxacin (400mg 12-hourly) may be used as an alternative if there is a contraindication to cephalosporins (e.g. allergy). Patients already receiving an alternative IV antibiotic to treat infection will not receive this additional IV antibiotic, but will continue the prescribed antibiotic for the usual duration of therapy.
Intervention Type
Drug
Intervention Name(s)
SDD Oral Paste
Other Intervention Name(s)
Colistin, Tobramycin and Nystatin
Intervention Description
A six-hourly topical application of 0.5g paste, containing colistin 10mg, tobramycin 10mg and nystatin 125,000 IU, to the buccal mucosa and oropharynx
Intervention Type
Drug
Intervention Name(s)
SDD Gastric Suspension
Other Intervention Name(s)
Colistin, Tobramycin and Nystatin
Intervention Description
2. A six-hourly administration of 10 mL of a suspension containing 100 mg colistin, 80 mg tobramycin and 2 x 10 ^6 IU nystatin, to the gastrointestinal tract via a gastric/post-pyloric tube
Intervention Type
Drug
Intervention Name(s)
Intravenous Antibiotic
Other Intervention Name(s)
Ceftriaxone, Cefotaxime or Ciprofloxacin
Intervention Description
A four-day course of an intravenous antibiotic in patients not already receiving a therapeutic antibiotic
Primary Outcome Measure Information:
Title
Hospital Mortality
Description
all-cause mortality at time of hospital discharge
Time Frame
Hospital discharge [up to Day 90 after randomization]
Secondary Outcome Measure Information:
Title
Total antibiotic usage
Description
Total antibiotic usage (as daily defined doses) during ICU admission in all ICU admissions.
Time Frame
during ICU admission
Title
The incidence of antibiotic resistant organisms in cultures from blood or other sterile sites
Description
The incidence of antibiotic resistant organisms in cultures from blood or other sterile sites during ICU admission in all ICU admissions.
Time Frame
during ICU admission
Title
The incidence of antibiotic-resistant organism in non-sterile clinical and surveillance specimens
Description
The incidence of antibiotic-resistant organism in non-sterile clinical and surveillance specimens during ICU admission in all ICU admissions
Time Frame
during ICU admission
Title
The incidence of C. difficile infections
Description
The incidence of C. difficile infections during ICU admission in all ICU admissions
Time Frame
during ICU admission
Title
Changes in antibiotic resistance rates between study epochs (pre-trial, interperiod gap and post-trial) within groups
Description
Changes in ARO rates between time epochs (pre-trial, trial, inter-period gap and post-trial) within groups. With control group data to give the secular trend in ARO with time and SDD group data studying the effects of SDD withdrawal from practice in the year after SDD delivery
Time Frame
Through out all study periods
Title
Duration of mechanical ventilation
Description
Duration that the patient is mechanically ventilated in the ICU
Time Frame
Time of enrolment to ICU discharge within index hospital admission,[up to Day 90 after randomization]
Title
ICU length of stay
Description
The length of time a patient stays in the ICU
Time Frame
From the time of enrolment to ICU discharge, [up to Day 90 after randomization]
Title
Hospital length of stay
Description
The total hospital length of stay for patient
Time Frame
From time of enrolment to hospital discharge within the index hospital admission, [up to Day 90 after randomization]
Title
ICU Mortality
Description
mortality at time of ICU discharge
Time Frame
ICU discharge [up to Day 90 after randomization]

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Site inclusion for cluster study- A general ICU or complex of ICUs (medical, surgical, mixed) capable of treating mechanically ventilated critically ill adult patients. Patient inclusion criteria All patients who are mechanically ventilated via an endotracheal tube on admission to ICU and who are predicted to remain ventilated beyond the end of the calendar day after the day of ICU admission, or All patients who become mechanically ventilated via an endotracheal tube during their ICU stay and who are predicted to remain ventilated beyond the end of the calendar day after the day they are first ventilated, or All patients not already recruited who are receiving mechanical ventilation via an endotracheal tube and are expected to receive ongoing ventilation for a further 48 hours or more despite an earlier prediction that ventilation would be discontinued earlier. Site exclusion criteria for cluster study- Unwilling or unable to follow trial protocols. Unable to capture the minimum data set required for the study. Isolated specialty ICUs not co-located with a general ICU, such as solely cardiac, neurological/neurosurgical and burns ICUs, but such specialty patients cared for in general ICUs will be included Specialty paediatric ICUs Exclusion Criteria: Patient exclusion criteria Patients enrolled in a trial that would interact with the intervention Patients with a known allergy, sensitivity or interaction to trial topical intervention drugs Patients who are known or suspected to be pregnant Patients who are moribund and not expected to survive the next 12 hours Patients less than 16 years of age will not be enrolled in the UK
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Myburgh, MBBCh PhD
Organizational Affiliation
The George Institute
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Brian Cuthbertson, MD FRCA
Organizational Affiliation
Sunnybrook Health Sciences Centre
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Anthony Gordon, MD FRCA
Organizational Affiliation
Imperial College London
Official's Role
Study Chair
Facility Information:
Facility Name
The George Institute for Global Health
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2000
Country
Australia
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Imperial College London
City
London
ZIP/Postal Code
W21PG
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The protocol and statistical analysis plan were made public in 2020. The participant level dataset will not be publicly available immediately but will be available to collaborative researchers after consultation and negotiation with the SuDDICU Investigators.
IPD Sharing Time Frame
The SuDDICU Protocol V4.0 and SAP V1.1 are available on the open science framework in pre print.
IPD Sharing Access Criteria
Public access, no access criteria to view the SuDDICU Protocol V4.0 and SAP V1.1
IPD Sharing URL
https://osf.io/
Citations:
PubMed Identifier
24207137
Citation
Cuthbertson BH, Campbell MK, MacLennan G, Duncan EM, Marshall AP, Wells EC, Prior ME, Todd L, Rose L, Seppelt IM, Bellingan G, Francis JJ. Clinical stakeholders' opinions on the use of selective decontamination of the digestive tract in critically ill patients in intensive care units: an international Delphi study. Crit Care. 2013 Nov 8;17(6):R266. doi: 10.1186/cc13096.
Results Reference
result
PubMed Identifier
23352693
Citation
Daneman N, Sarwar S, Fowler RA, Cuthbertson BH; SuDDICU Canadian Study Group. Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis. Lancet Infect Dis. 2013 Apr;13(4):328-41. doi: 10.1016/S1473-3099(12)70322-5. Epub 2013 Jan 25.
Results Reference
result
PubMed Identifier
21129208
Citation
Cuthbertson BH, Francis J, Campbell MK, MacIntyre L, Seppelt I, Grimshaw J; SuDDICU study groups. A study of the perceived risks, benefits and barriers to the use of SDD in adult critical care units (the SuDDICU study). Trials. 2010 Dec 3;11:117. doi: 10.1186/1745-6215-11-117.
Results Reference
result
PubMed Identifier
36286097
Citation
SuDDICU Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group; Myburgh JA, Seppelt IM, Goodman F, Billot L, Correa M, Davis JS, Gordon AC, Hammond NE, Iredell J, Li Q, Micallef S, Miller J, Mysore J, Taylor C, Young PJ, Cuthbertson BH, Finfer SR. Effect of Selective Decontamination of the Digestive Tract on Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial. JAMA. 2022 Nov 15;328(19):1911-1921. doi: 10.1001/jama.2022.17927.
Results Reference
derived

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Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients

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