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Trial registered on ANZCTR


Registration number
ACTRN12615000411549
Ethics application status
Approved
Date submitted
16/04/2015
Date registered
30/04/2015
Date last updated
6/12/2019
Date data sharing statement initially provided
6/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The SuDDICU Study of Antibiotic Prophylaxis in Critical Illness
Scientific title
A crossover, cluster randomised controlled trial of selective decontamination of the digestive tract in intensive care patients (SuDDICU)
Secondary ID [1] 286305 0
ClinicalTrials.gov Identifier- NCT02389036
Universal Trial Number (UTN)
Trial acronym
SuDDICU
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Known or suspected infection in critically ill patients in the Intensive Care Unit (ICU) 294396 0
Condition category
Condition code
Infection 294705 294705 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
SDD intervention group;
All patients in the intervention group will receive all 3 treatments. all treatment will occur simultaneously. The topical and enteral intervention will continue until tracheal extubation, removal of the enteral feeding tube, 24-hours unsupported spontaneous ventilation via tracheostomy, or ICU discharge, whichever comes first, for a maximum of 90 days. The IV Antibiotic intervention will be continued for 4 days. The study treatments will be administered by qualified ICU nurse.

The intervention will entail:
1. SDD paste: 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
2. SDD suspension: The six-hourly administration of 10 mls
suspension containing 100 mg colistin/ polymixin, 80 mg
tobramycin and 2 x 106 IU nystatin, to the gastrointestinal
tract via the gastric / jejunal tube.
3. A four-day course of an intravenous 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 intravenous antibiotic to treat infection will not receive this additional intravenous antibiotic, but will continue the prescribed antibiotic for the usual duration of therapy
Intervention code [1] 291344 0
Treatment: Drugs
Comparator / control treatment
In Australia there are no national guidelines so local policy is determined by each ICU. In these countries 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
Control group
Active

Outcomes
Primary outcome [1] 294469 0
all-cause mortality at time of hospital discharge
Timepoint [1] 294469 0
Hospital discharge
Secondary outcome [1] 313385 0
The incidence of AROs isolated from all clinical and surveillance specimens, including the incidence of AROs in cultures from blood or other sterile sites, the incidence of AROs in non-sterile clinical and surveillance specimens, and the incidence of bacteraemia in all blood culture specimens
Timepoint [1] 313385 0
Antibiotic resistance rates will be monitored - isolated from clinical and surveillance specimens during the first week of each month over three 3-month surveillance periods before, during the inter-period gap and after the second 12-month interventional period. within each centre.
Secondary outcome [2] 314167 0
Total antibiotic usage (as daily defined doses) - the data will be collected from patient medical records
Timepoint [2] 314167 0
Total antibiotic usage during ICU admission
Secondary outcome [3] 314170 0
The incidence of C. difficile infections- the data will be collected from hospital medical records
Timepoint [3] 314170 0
The incidence of C. difficile infections during ICU admission in all ICU admissions
Secondary outcome [4] 328345 0
Duration of mechanical ventilation
Timepoint [4] 328345 0
During ICU admission
Secondary outcome [5] 328346 0
ICU length of stay
Timepoint [5] 328346 0
ICU discharge
Secondary outcome [6] 328347 0
ICU mortality
Timepoint [6] 328347 0
ICU discharge
Secondary outcome [7] 328348 0
Hospital length of stay
Timepoint [7] 328348 0
Hospital discharge
Secondary outcome [8] 328349 0
Health economic analysis from a healthcare system perspective
Timepoint [8] 328349 0
After study completion

Eligibility
Key inclusion criteria
Site inclusion for cluster study:
A general ICU or complex of ICUs (medical, surgical, mixed) capable of treating mechanically ventilated critically ill 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.
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 (non 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

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

Patients readmitted to the ICU will be re-enrolled into the study and receive study interventions if they meet inclusion criteria and do not have any exclusion criteria. They will be counted as the same enrolment for study analysis.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The study is a cross-over cluster randomised trial. ICUs will be randomised to either deliver SDD in the first 12-month period and be a control ICU in the second 12-month period, or to be a control ICU first and deliver SDD in the second period.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
All participating ICUs will be randomised at the same time by an independent statistician using a computer-based randomisation program. ICUs will be notified to which order of periods they have been allocated during the 3-month pre-trial phase.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
We will not blind the intervention. Because of the nature of the cluster trial, blinding is not necessary as the control or intervention protocol will be followed by the entire cluster.
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
SuDDICU will recruit 10 000-15 000 patients from 40-50 ICUs in Australia, UK and Canada that will detect a 3% absolute reduction in hospital mortality from a baseline mortality of 29%, using 80% power, a <0.05.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 3704 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 3706 0
Nepean Hospital - Kingswood
Recruitment hospital [3] 3708 0
Gosford Hospital - Gosford
Recruitment hospital [4] 3709 0
John Hunter Hospital Royal Newcastle Centre - New Lambton
Recruitment hospital [5] 3711 0
St George Hospital - Kogarah
Recruitment hospital [6] 6817 0
Liverpool Hospital - Liverpool
Recruitment hospital [7] 6819 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [8] 6820 0
Bendigo Health Care Group - Bendigo Hospital - Bendigo
Recruitment hospital [9] 6821 0
Footscray Hospital - Footscray
Recruitment hospital [10] 6822 0
Sunshine Hospital - St Albans
Recruitment hospital [11] 6823 0
Epworth Richmond - Richmond
Recruitment hospital [12] 6824 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [13] 15423 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [14] 15424 0
Wollongong Hospital - Wollongong
Recruitment hospital [15] 15425 0
The Wesley Hospital - Auchenflower
Recruitment hospital [16] 15426 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [17] 15427 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 14481 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 14482 0
3550 - Bendigo
Recruitment postcode(s) [3] 14483 0
3011 - Footscray
Recruitment postcode(s) [4] 14484 0
3021 - St Albans
Recruitment postcode(s) [5] 14485 0
3121 - Richmond
Recruitment postcode(s) [6] 14486 0
5042 - Bedford Park
Recruitment postcode(s) [7] 28746 0
2065 - St Leonards
Recruitment postcode(s) [8] 28747 0
2050 - Camperdown
Recruitment postcode(s) [9] 28748 0
2340 - Kingswood
Recruitment postcode(s) [10] 28749 0
2250 - Gosford
Recruitment postcode(s) [11] 28750 0
2305 - New Lambton
Recruitment postcode(s) [12] 28751 0
2217 - Kogarah
Recruitment postcode(s) [13] 28752 0
2500 - Wollongong
Recruitment postcode(s) [14] 28753 0
4066 - Auchenflower
Recruitment postcode(s) [15] 28754 0
5000 - Adelaide
Recruitment postcode(s) [16] 28755 0
5011 - Woodville
Recruitment outside Australia
Country [1] 22168 0
Canada
State/province [1] 22168 0
Toronto
Country [2] 22169 0
United Kingdom
State/province [2] 22169 0
No new state

Funding & Sponsors
Funding source category [1] 291107 0
Government body
Name [1] 291107 0
National Health and Medical Research Council (NHMRC)
Address [1] 291107 0
Level 1
16 Marcus Clarke Street
Canberra ACT 2601
Country [1] 291107 0
Australia
Primary sponsor type
Other Collaborative groups
Name
The George Institute for Global Health
Address
Level 5,
1 King St
Newtown NSW 2042
Country
Australia
Secondary sponsor category [1] 289784 0
None
Name [1] 289784 0
Address [1] 289784 0
Country [1] 289784 0
Other collaborator category [1] 281088 0
University
Name [1] 281088 0
Imperial College London
Address [1] 281088 0
South Kensington Campus
London SW7 2AZ, UK
Country [1] 281088 0
United Kingdom
Other collaborator category [2] 281089 0
Hospital
Name [2] 281089 0
Sunnybrook Health Sciences Centre
Address [2] 281089 0
C Block, Level 8, 2075 Bayview Av, Toronto M4N 3M5
Country [2] 281089 0
Canada

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292686 0
Sydney Local Health Disctrict Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 292686 0
Research Development office
Royal Prince Alfred Hospital
Camperdown NSW 2050
Ethics committee country [1] 292686 0
Australia
Date submitted for ethics approval [1] 292686 0
09/03/2015
Approval date [1] 292686 0
18/12/2015
Ethics approval number [1] 292686 0
HREC/15/RPA/110
Ethics committee name [2] 296119 0
Royal Brisbane and Women's Hospital Human Research Ethics Committee (BRWH HREC)
Ethics committee address [2] 296119 0
Royal Brisbane and Women's Hospital
Level 7, Block 7
Butterfield Street, Herston
QLD 4029
Australia
Ethics committee country [2] 296119 0
Australia
Date submitted for ethics approval [2] 296119 0
22/03/2015
Approval date [2] 296119 0
15/06/2015
Ethics approval number [2] 296119 0
HREC/15/QRBW/241

Summary
Brief summary
Selective Decontamination of the Digestive Tract (SDD) is a treatment designed to reduce the risk of infection and improve survival for critically ill patients. SDD is the application of antibiotics and antifungal drugs to the throat and their instillation into the stomach, combined with a short course of intravenous antibiotics.

Although many trials suggest that SDD works, the research results have not been convincing enough to lead to the widespread uptake of SDD around the world. Additionally clinicians are concerned that SDD will increase antibiotic resistance amongst endemic bacteria. As a result, SDD is not currently widely practiced.

This trial aims to resolve this uncertainty. We will be conducting the definitive randomised study examining the effect of implementing SDD. For 24 months, ICUs in Australia will be randomly assigned to either deliver SDD in the first 12-month period and be a control ICU in the second 12-month period, or to be a control ICU first and deliver SDD in the second period. 8000 critically ill mechanically ventilated patients will be enrolled. Mortality rates will be compared between the SDD and control groups antibiotic resistance rates will be evaluated in samples from all patients prior to, during and after the trial to determine the effect of SDD on the microbial ecology.
The SuDDICU trial will provide definitive answer to a fundamental question in intensive care medicine - does SDD reduce critically ill patients’ risk of dying without increasing antibiotic resistance rates? If SDD is found to be effective without increasing antibiotic resistance, the study will have a global impact, leading to improved survival and reduced infection rates in critically ill patients. The results of this study will change practice and be of immense value to clinicians, policy makers and regulators.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 55502 0
A/Prof Ian Seppelt
Address 55502 0
The George Institute for Global Health
Level 5, 1 King St
Newtown
NSW 2042 Australia
Country 55502 0
Australia
Phone 55502 0
+61 2 8238 2467
Fax 55502 0
Email 55502 0
ian.seppelt@sydney.edu.au
Contact person for public queries
Name 55503 0
Ms Fiona Goodman
Address 55503 0
The George Institute for Global Health
Level 5, 1 King St
Newtown
NSW 2042 Australia
Country 55503 0
Australia
Phone 55503 0
+61 2 80524768
Fax 55503 0
Email 55503 0
fgoodman@georgeinstutite.org.au
Contact person for scientific queries
Name 55504 0
A/Prof Ian Seppelt
Address 55504 0
The George Institute for Global Health
Level 5, 1 King St
Newtown
NSW 2042 Australia
Country 55504 0
Australia
Phone 55504 0
+61 2 8238 2467
Fax 55504 0
Email 55504 0
ian.seppelt@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results