The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12617000373370
Ethics application status
Approved
Date submitted
6/03/2017
Date registered
13/03/2017
Date last updated
31/01/2019
Date data sharing statement initially provided
31/01/2019
Date results information initially provided
31/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Catheter associated urinary tract infections: the role of chlorhedixdine in reducing urinary infections in hospitalised patients.
Scientific title
Efficacy and cost-effectiveness of cleaning the urethral meatal area with chlorhexidine prior to urinary catheter insertion for the prevention of catheter-associated infections.
Secondary ID [1] 291238 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Catheter associated asymptomatic bacteriuria 302360 0
Catheter associated urinary tract infections 302361 0
Condition category
Condition code
Infection 301776 301776 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention will consist of clinical staff using a 0.1% chlorhexidine solution for meatal cleaning i.e. the urethral insertion site area will be swabbed using chlohexidine immediaely prior to urinary catheter insertion. Fidelity of the swabbing process will not be assessed. due to patient privacy issues.
Intervention code [1] 297243 0
Treatment: Other
Intervention code [2] 297416 0
Treatment: Drugs
Comparator / control treatment
The control will consist of clinical staff using a 0.9% normal saline solution for meatal cleaning prior to urinary catheter insertion. Each hospital will act as its own control.
Control group
Active

Outcomes
Primary outcome [1] 301179 0
The number of cases of catheter associated asymptomatic bacteriuria (CA-ASB) per 100 catheter days.
Results of all positive urine cultures either attributable to bacteriuria are registered in the hospital microbiology laboratory databases. Results of individual participants will be reviewed to determine the presence or absence of bacteriuria in any submitted urine sample to the laboratory.

CA-ASB is defined as the presence of greater than or equal to 10 X 5 colony forming unit (cfu)/ml of one or more bacterial species in a single catheter urine specimen in a patient without symptoms compatible with UTI.

Timepoint [1] 301179 0
The monthly incidence of catheter associated asymptomatic bacteriuria (CA-ASB) per 100 catheter days is used as the clusters in the eight month study. i.e.. monthly incidence for 8 months (study duration).

Primary outcome [2] 301180 0
The number of cases of catheter associated urinary tract infections (CAUTI) per 100 catheter days.

Results of all positive urine cultures either attributable to bacteriuria are registered in the hospital microbiology laboratory databases. Results of individual participants will be reviewed to determine the presence or absence of bacteriuria in any submitted urine sample to the laboratory. Further, a review of medical notes will occur to determine signs or symptoms of a CAUTI.

A CAUTI is defined according to National Healthcare Safety Network criteria. A patient must meet all three criteria below:
1. Patient had an indwelling urinary catheter that had been in place for > 2 days on the date of event (day of device placement = Day 1) AND was either present for any portion of the calendar day on the date of event or removed the day before the date of event.
2. Patient has at least one of the following signs or symptoms: fever (>38.0 degree celsius); suprapubic tenderness; costovertebral angle pain or tenderness; urinary urgency; urinary frequency; dysuria.
3. Patient has a urine culture with no more than two species of organisms identified, at least one of which is a bacterium of greater than or equal to =10 X 5 cfu/ml.
Timepoint [2] 301180 0
The monthly incidence of catheter associated urinary tract infections (CAUTI) per 100 catheter days is used as the clusters in the eight month study. i.e.. monthly incidence for 8 months (study duration).
Primary outcome [3] 301181 0
Changes in costs relative to health benefits (incremental cost-effectiveness ratio) from adoption of the intervention.

The effectiveness data from outcome 1 and 2 will be a key parameter in a cost-effectiveness model. Final outcomes for the cost-effectiveness evaluation are the incremental cost-effectiveness ratio estimated as the cost per QALY gained, and the changes to costs and in QALYs. The changes to costs from adopting the intervention will be estimated by the extra staff time spent both planning and implementing the intervention, converted to a dollar figure using full employment costs. Other costs are product costs.
Timepoint [3] 301181 0
These cost data will be collected prospectively on a monthly basis for product costs and a survey immediately after the intervention is implemented (staff costs).
Secondary outcome [1] 331968 0
The number of bloodstream infections (BSI) associated with a UTI.

A BSI associated with a urinary tract infection (UTI) is defined according to National Healthcare Safety Network criteria. A patient must meet the definition for CAUTI and have at least one organism from the blood specimen that matches an organism identified in the urine specimen that is used as an element to meet the CAUTI criterion.
Timepoint [1] 331968 0
The monthly incidence of bloodstream infections (BSI) associated with a UTI per 100 catheter days is used as the clusters in the eight month study. i.e.. monthly incidence for 8 months (study duration).

Eligibility
Key inclusion criteria
The hospital must meet the following inclusion criteria:
1. Has an intensive care unit.
2. Is classified by the Australian Institute of Health and Welfare as a principal referral hospital OR a public acute group A hospital (with more than 400 beds), OR in the case of a private hospital has 400 inpatient beds OR has more than 30,000 patient admissions per year.


Minimum age
2 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The study will be a hospital wide study, but with the following exclusion criteria:
- Patients that do not require a catheter.
- Individual areas within a hospital that are not considered appropriate for the intervention
- Neonatal intensive care departments
- Any patient less than 2 years old
- Patients with indwelling urinary catheters inserted in theatre.
- Patients with an allergy, contraindication or other medical reason preventing the use of the intervention for cleaning the urethral meatal area will be excluded.
Patients who require in-and-out or suprapubic catheterisation will also be excluded as well as those with symptoms and signs suggestive of UTI and patients already undergoing treatment for UTI.
Hospitals could be excluded from the study if within the study time frame they are; undertaking a project that may influence the outcomes measured in this study; opening, closing or relocating


Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
A stepped wedge cluster randomised controlled study.

A stepped wedge randomised controlled trial will be undertaken in three large tertiary hospitals over a 32-week period. The stepped wedge design includes an initial period where no hospitals are exposed to the intervention. Afterwards, at regular intervals (the “steps”) one or more hospitals are randomised to cross over from the control to the intervention with the process continuing until all hospitals have crossed over. . There will be a random sequential allocation of the intervention to three hospitals, that is, each hospital will be introduced to the intervention approximately every eight weeks until week 32, when all three hospitals would have been exposed to the intervention. The study design enables each hospital to act as its own control, which removes the potential for some confounders such as variations in hospital size and case mix and differences between public and private hospitals. Staggered commencement and duration of the intervention, supports feasibility while maintaining the rigour of the study. This design will allow research staff to work with individual hospitals as they change over, maximising consistency of intervention and aiding implementation. In addition, data collection continues throughout the study, so that each cluster contributes observations under both control and intervention observation periods.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Objective 1
The number of cases of catheter associated asymptomatic bacteriuria and catheter associated urinary tract infections will be analysed using Poisson regression, with the number of cases as the dependent variable and number of patient catheter days as the denominator. This denominator will help control for changes in catheter use during the study period. The key independent variable will be the intervention. The key outcome will be the estimated reduction in cases due to the intervention. The characteristics of the hospital (e.g. size) will not be independent variables as these should remain roughly constant throughout the study observations. There is no expected delay in the effect of intervention on the outcome.


Objective 2
The effectiveness data from Objective 1 will be a key parameter in a cost-effectiveness model. Final outcomes for the cost-effectiveness evaluation are the incremental cost-effectiveness ratio estimated as the cost per QALY gained, and the changes to costs and in QALYs. Published guidelines for costing an intervention will be followed.. The changes to costs from adopting the intervention will be estimated by the extra staff time spent both planning and implementing the intervention, converted to a dollar figure using full employment costs. Other costs are product costs. These cost data will be collected prospectively on a monthly basis for product costs and a survey immediately after the intervention is implemented (staff costs). Quantities of resources will be standardised to all hospitals to ensure valid comparison of costs across all sites. This will reduce uncertainty in estimates which often results from using retrospective administrative data.

The major cost savings from reducing infections are characterised by the bed days saved from keeping patients infection free and hence discharging them earlier. The reasoning is that 90% of the costs of hospital services are fixed and so bed days saved are an appropriate currency. Data from a previous study using multistate modelling to estimate the extra length of stay per case of urinary bacteriuria will be used in the model. Other cost savings are averted laboratory diagnosis costs and antimicrobial therapy costs, estimated by counting the frequency of laboratory tests and antimicrobial therapy costs in the control and intervention periods. These will be collected prospectively as part of the data collection process. Laboratory costs using the relevant Medical Benefit Scheme item costs will be used. For antimicrobial therapy costs, Pharmaceutical Benefits Scheme costs will be used.

Changes to health benefits will be informed by the extra death risk due to infection. This parameter will come from a previously described analysis of mortality associated with urinary bacteriuria. These estimates used multi-state models that avoid time and length biases to estimate increases in mortality attributable to infection. The results are hazard ratios that can be used to predict reduction in deaths from avoided infections. The mean age of hospital patients will be used to predict years of life gained and preference based utility scores will be used to weight life expectancy, allowing us to calculate QALYs. We will not collect primary data on preference based utility scores. Instead, these estimates will be taken from the published literature.

The change to total costs at the hospital level will be estimated by summing intervention costs and deducting cost savings from reduced lengths of stay and use of health care resources that arise from reduced incidences of infection. The changes to health benefits will be estimated in QALYs using: the number of life years saved from reduced infection outcomes; the expected duration of life (had infection not occurred) based on age and data from the published literature. All costs and health benefits arising in future periods will be appropriately discounted. Uncertainties in parameter estimates will be captured using appropriate statistical distributions to describe the variability. For example, the beta distribution would be a good choice for infection risk as this distribution is restricted to interval 0–1. The parameters of the beta distribution will be chosen to reflect what we know about the mean and range in infection risk (e.g., a beta distribution with a mean rate of infection of 0.003 and 95% confidence interval of 0.001 to 0.005). The fitted distributions will be subject to random re-samples simulated 10,000 times. The distributions of all prior parameters are used to estimate the posterior distributions of ‘change to costs’ and ‘change to QALY’ outcomes.

The decision will be informed by plotting cost-effectiveness acceptability curves with threshold value between zero and 100,000 per QALY gained, and using the net monetary benefits framework. These approaches are semi Bayesian and appropriately account for all parameter uncertainty for the adoption decisions.

Recruitment
Recruitment status
Completed
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)
ACT,NSW
Recruitment hospital [1] 10123 0
The Canberra Hospital - Garran
Recruitment hospital [2] 10124 0
Sydney Adventist Hospital - Wahroonga
Recruitment hospital [3] 10125 0
Lismore Base Hospital - Lismore
Recruitment postcode(s) [1] 21658 0
2605 - Garran
Recruitment postcode(s) [2] 21659 0
2076 - Wahroonga
Recruitment postcode(s) [3] 21660 0
2480 - Lismore

Funding & Sponsors
Funding source category [1] 295689 0
Charities/Societies/Foundations
Name [1] 295689 0
HCF Foundation
Address [1] 295689 0
403 George Street
Sydney
NSW 2000
Country [1] 295689 0
Australia
Primary sponsor type
University
Name
Avondale College
Address
582 Freemans Drive (PO Box 19),
Cooranbong NSW 2265,
Country
Australia
Secondary sponsor category [1] 294700 0
None
Name [1] 294700 0
Address [1] 294700 0
Country [1] 294700 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296999 0
Avondale College of Higher Education HREC
Ethics committee address [1] 296999 0
582 Freemans Drive (PO Box 19)
Cooranbong NSW 2265,
Australia
Ethics committee country [1] 296999 0
Australia
Date submitted for ethics approval [1] 296999 0
22/02/2017
Approval date [1] 296999 0
08/03/2017
Ethics approval number [1] 296999 0
2017:3
Ethics committee name [2] 299730 0
Adventist Healthcare
Ethics committee address [2] 299730 0
Research Ethics and Governance Office
Adventist healthcare
Fox Valley Road
Wahroonga
Sydney
NSW 2076
Ethics committee country [2] 299730 0
Australia
Date submitted for ethics approval [2] 299730 0
10/04/2017
Approval date [2] 299730 0
30/05/2017
Ethics approval number [2] 299730 0
2017-018 NEAF ID REF NO: AU/1/A9FC21
Ethics committee name [3] 299731 0
ACT Health HREC
Ethics committee address [3] 299731 0
Research Ethics and Governance Office
Building 10, Level 6
Canberra hospital
Yamba Drive
Garran
ACT 2605
Ethics committee country [3] 299731 0
Australia
Date submitted for ethics approval [3] 299731 0
27/03/2017
Approval date [3] 299731 0
16/05/2017
Ethics approval number [3] 299731 0
ETH.4.17.083
Ethics committee name [4] 299732 0
ACT Health HREC
Ethics committee address [4] 299732 0
Research Ethics and Governance Office
Building 10, Level 6
Canberra Hospital
Yamba drive
Garran
ACT 2605
Ethics committee country [4] 299732 0
Australia
Date submitted for ethics approval [4] 299732 0
16/05/2017
Approval date [4] 299732 0
22/07/2017
Ethics approval number [4] 299732 0
ETH.4.17.083-NMA-HREC/17/ACT/24

Summary
Brief summary
Approximately 1% of all patients (around 95,000 per year), who go to hospital acquire a urinary tract infection (UTI). It has been suggested that up to 80% of hospital associated UTS’s are caused by the use of a urinary catheter. Insertion of the catheter is an important part of reducing the risk of infection. There is wide variation in practice relating to cleaning the urethral meatus area before catheter insertion. This study intends to ascertain if cleaning the urethral meatus with saline 0.9% (Control) or an antiseptic chlorhexidine 0.1% (Intervention) reduces the instances of infection. The benefits relating to the outcomes of this study are to reduce the risk of infection and therefore it’s associated cost savings.

The research hypotheses
1. When undertaking meatal cleaning prior to indwelling urinary catheter insertion, there is no difference between the use of normal saline (0.9%) and chlorhexidine (0.1%) solution on the incidence of catheter-associated urinary tract infections (CAUTIs).
2. The use of chlorhexidine (0.1%) solution for meatal cleaning prior to urinary catheter insertion is not a cost-effective intervention to reduce CAUTI.

Study design
A multi-site stepped wedge randomised controlled trial will be undertaken in three large tertiary hospitals (approximately 2640 participants) over a 32-week period, with a random sequential allocation of the intervention to three hospitals. The study design enables each hospital to act as its own control, which removes the potential for some confounders such as variations in hospital size and case mix and differences between public and private hospitals. Staggered commencement and duration of the intervention, either 2,4 or 6 months, supports feasibility while maintaining the rigour of the study.
The number of catheter associated UTIs will be analysed using Poisson regression, with the number of cases as the dependent variable and number of patient catheter days as the denominator. This denominator will help control for changes in catheter use during the study period. The key independent variable will be the intervention.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72666 0
Prof Brett Mitchell
Address 72666 0
Avondale College of Higher Education
Discipline of Nursing
Clinical Education Centre
185 Fox Valley Road
Wahroonga
NSW 2076
Country 72666 0
Australia
Phone 72666 0
+61 2 9480 3613
Fax 72666 0
Email 72666 0
brett.mitchell@avondale.edu.au
Contact person for public queries
Name 72667 0
Prof Brett Mitchell
Address 72667 0
Avondale College of Higher Education
Discipline of Nursing
Clinical Education Centre
185 Fox Valley Road
Wahroonga
NSW 2076
Country 72667 0
Australia
Phone 72667 0
+61 2 9480 3613
Fax 72667 0
Email 72667 0
brett.mitchell@avondale.edu.au
Contact person for scientific queries
Name 72668 0
Prof Brett Mitchell
Address 72668 0
Avondale College of Higher Education
Discipline of Nursing
Clinical Education Centre
185 Fox Valley Road
Wahroonga
NSW 2076
Country 72668 0
Australia
Phone 72668 0
+61 2 9480 3613
Fax 72668 0
Email 72668 0
brett.mitchell@avondale.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
Protocol paper is published (British Medical Journal Open)
Results still pending formal publication in peer reviewed journals
Statistical plans to be published as part of main results publication (supplementary material)
Ethics study approval required waiver of consent approval which did not extend to sharing of data.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary