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Trial registered on ANZCTR


Registration number
ACTRN12622000715774
Ethics application status
Approved
Date submitted
5/04/2022
Date registered
18/05/2022
Date last updated
3/05/2023
Date data sharing statement initially provided
18/05/2022
Date results information initially provided
3/05/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
The VRESIST trial: Evaluating the effectiveness of a hospital-based antimicrobial stewardship intervention upon antibiotic use in Vietnam
Scientific title
A cluster randomised controlled trial of the effect of an Antimicrobial Stewardship interventions upon antibiotic use in district health facilities in Vietnam
Secondary ID [1] 306849 0
None
Universal Trial Number (UTN)
U1111-1276-6380
Trial acronym
VRESIST Study C
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Antimicrobial resistance 325896 0
Condition category
Condition code
Infection 323203 323203 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention comprises an Antimicrobial Stewardship (AMS) program that includes:
1. Formation and training of a local AMS committee and AMS team
- The AMS Committee will be appointed by the District Hospital leader. Members will include hospital administrators, heads of departments, doctors and pharmacists from the hospital that have an understanding of their respective hospital's antibiotic use and knowledge on antimicrobial stewardship. Furthermore, an AMS team will be formed which will include at least one doctor and one pharmacist who will conduct the audits. Individuals are selected based upon their clinical experience using antimicrobials.
Research team will organise one presentation to the AMS committee to present an overview of VRESIST C Study that will be 30 minutes long. The AMS committee continues to meet monthly during the intervention to discuss AMS issues, review the audits and surveys of healthcare workers in their hospital. This meeting will be no more than 2 hours.
As for the AMS team:
Initial training comprises (i) a 1-hour offline training powerpoint session by the research team Topics during training will include (a) knowledge about appropriate antimicrobial prescribing; (b) instructions about the audit and feedback process; (c) using study and Ministry of Health(MoH) guidelines for the audits
- Following the initial training session, additional training will be provided based upon the results of the baseline audit. This will include feedback regarding the accuracy of the audit process and tips for improving the audit process.

2. Introduction of comprehensive guidelines for antibiotic use to treat common infectious conditions
- Treatment guidelines were developed specifically for the study, based upon national Vietnam Ministry of Health antibiotic guidelines. For guidelines that are not available in the study, MoH guidelines are used.
- A physical copy of the treatment guidelines will be given to doctors, doctor assistants and pharmacists in hospitals in the intervention sites. Control sites will use their current standard of care, comprising national or local guidelines according to their standard practice.
- The treatment guidelines will be distributed by the hospital administrators to departments for all relevant healthcare workers. Digital copies were presented to the hospital administrators to make further physical copies of these guidelines if required for distribution.

3. Regular audits of antimicrobial use, including an analysis of the appropriateness of antimicrobial use and adherence to guidelines, with collective feedback to prescribers
- The audit tool is adapted from National Antimicrobial Prescriber Survey (NAPS) Australia. Audits will be conducted by the hospital’s AMS team as well as at least one of our study team members.
-In intervention sites, audits will occur at the start of the study (baseline), after 2 months, as well as at the end of the intervention period (4 months) in the intervention sites.
- In control sites, the audits will only be conducted at baseline (by an audit team not based at the hospital, without providing the results to staff) and at the end of the intervention (Month 4)
- Audits will be carried out on hospital records including patient files and medication charts. Information including antibiotics, duration, indication, procedures or surgeries if applicable are noted down. Then, an assessment on the antibiotic appropriateness is done according to the NAPS appropriateness guideline. No interviews or patient interaction will occur
- Feedback sessions will be carried out after the audits in a collective session - such as hospital grand rounds or departmental meetings to identify areas where antibiotic prescription can be improved.

4. Healthcare worker education and training regarding appropriate antimicrobial use
- In intervention sites, 2 workshops will be carried out in the 4 month intervention period. The first workshop will happen a month into the intervention, and the second one in the third month of intervention. Each session will be an hour and be carried out face to face. This will go through the antibiotic guidelines, principles of antimicrobial stewardship as well as the audit feedback process. It will also include case study examples as a tool for educating healthcare workers.
- In control sites, there will be no workshops during the intervention period. A workshop will be implemented during the post-intervention period (i.e. cross-over period), allowing for this approach to be implemented in the control districts.

5. Health promotion campaign focusing upon appropriate antimicrobial use for patients and clinicians.
The health promotion campaign in intervention sites (and in control sites during the cross-over period) will include:
- The research team will distribute posters during days of audits in each ward as well as outpatient departments and also pass it on to the hospital administrators to arrange for it to be displayed in high traffic areas of the hospital. These posters have important AMS messages such as not needing antibiotics for common viral infections, facts on antibiotics and on antibiotic resistance in lay terms.

Occurrence of each component
- Hospital facility surveys and surveys of healthcare workers in the facility pre-intervention
- Appointment of local AMS committee and AMS team done concurrently
- AMS team will be trained within the first 2 weeks
- Baseline NAPS audit performed soon after training
- Interventions begin within 2 weeks after baseline audit
- Introduction of antibiotic guidelines immediately after
- 2 Workshops (Month 1 and Month 3)
- Audit at Month 2 and feedback process
- Audit at Month 4 and feedback process

Strategies to monitor adherence
- Attendance records for workshops
- Feedback sessions within 2 weeks of audit to the doctors in departmental meetings where there will be opportunities for discussion with the AMS team
Intervention code [1] 323279 0
Treatment: Other
Comparator / control treatment
Routine antibiotic prescribing as per usual practice (current standard of care), and whatever current AMS strategies the hospital already has(most of them have minimal AMS strategies in place)


The crossover will occur 4 months after the intervention period, after the completion of the final NAPS audit and feedback process. At crossover the control group will be offered the same AMS program which includes formation of AMS committee, distribution of comprehensive antibiotic guidelines, healthcare worker training and education as well as NAPS audit and feedback
Control group
Active

Outcomes
Primary outcome [1] 330958 0
The proportion of patients with infectious diseases treated with appropriate antimicrobials according to a clinical audit of patient files, comparing the antimicrobial use in the period before and after the intervention period, assessed using an adapted version of the Australian National Antimicrobial Prescribing Survey (NAPS) tool.
Timepoint [1] 330958 0
Comparison between the pre-intervention audit (carried out prior to the intervention period), and the audit 4 months after the start of the intervention period.
Primary outcome [2] 330959 0
The difference in Defined Daily Doses (DDD) of antibiotics per 1,000 bed-days (or DOT for paediatric cohort) among inpatients attending district health facilities comparing the period before and after the 4-month intervention period, in the intervention group compared to the control group. The data is obtained from the hospital pharmacies who have data of amount of antibiotics prescribed in the hospital as well as hospital system database that has information on bed days. This information is sufficient to get DDD data without the need for individual medical record data linkage
Timepoint [2] 330959 0
Comparison of the DDD calculation for the 3 months leading up to the intervention period and the DDD calculation in the 3 months after the 4-month intervention period,
Secondary outcome [1] 408255 0
To evaluate differences in healthcare worker knowledge regarding appropriateness of antibiotics and avoidance of antibiotics for common viral infections, as assessed by standardized surveys, after compared to before the 4-month intervention period in the intervention compared to control group.
Timepoint [1] 408255 0
Knowledge, awareness and practice (KAP) surveys will be performed prior to the intervention, and repeated following the 4 month intervention period.
Secondary outcome [2] 408256 0
The difference in health system cost per DDD of antibiotics per 1,000 inpatients during the intervention period, in the intervention compared to the control group. Data is obtained from hospital pharmacy dispensing registry regarding the number of antibiotics used. The pharmacy financial records will be used to determine the cost of antimicrobials used.

Timepoint [2] 408256 0
Prior to the intervention period, compared to the end of the 4 month intervention period
Secondary outcome [3] 408426 0
The difference in 30-day all-cause mortality among inpatients, comparing mortality for patients admitted at baseline versus the end of the intervention period, in the intervention compared to the control group. Data is collected from the mortality register of the hospital
Timepoint [3] 408426 0
Prior to the intervention compared to at the end of the 4-month intervention period.
Secondary outcome [4] 408427 0
The proportion of clinical staff employed at District clinics attending one or more training workshops during the intervention period. This is monitored by evaluating the attendance records of each training session.
Timepoint [4] 408427 0
During the four month intervention period
Secondary outcome [5] 408429 0
The proportion patients reporting awareness of the AMS campaign. This outcome is assessed using a questionnaire which consists of multiple choice and yes/no questions. This questionnaire has been adapted from a WHO survey called WHO: Antibiotic resistance: multi-country public awareness survey: World Health Organisation: 2015. (Link: https://apps.who.int/iris/handle/10665/194460). This survey was adapted to the local context specifically for this study.
Timepoint [5] 408429 0
After the four-month intervention period - data collected once off within 2 weeks of the completion of intervention period

Eligibility
Key inclusion criteria
Eligibility of study health facilities:
- District health facility located within Hanoi or Ca Mau Provinces
- The facility has inpatients
- The leader of the facility agrees to participate in the study
- Selected by stratified random sampling

Eligibility of hospital wards to participate
- The leader of the ward agrees to participate
- The ward has inpatients
- Antimicrobials are available on the ward

Eligibility for inclusion of patient files in the antimicrobial stewardship audit:
- Patient is a current inpatient in the ward on the day of the audit
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Wards where antibiotics are not available.
- Wards that will be closed for at least 8 weeks during the intervention period.

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)
Central randomisation by a computer. The unit of randomisation (cluster) is the health facility (District hospital).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation using a computerised sequence generator, with balance in the number of inpatient beds and the number of district hospitals allocated to intervention and control groups.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Following the intervention period, a crossover will be performed to provide access to the intervention to the control sites.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
We expect that the intervention will reduce the proportion of antibiotics inappropriately prescribed from 66% (based upon baseline evaluation) to 52% (a 14% improvement). We expect the intraclass correlation coeffient to be up to 0.048 (ranged from 0.005 to 0.048 in a study of an AMS intervention among primary health providers) 15. Therefore, the sample size of patients' records included in the final audit that is required to detect this difference will be a total of 380 (including both intervention and control groups). When adjusted to account for intraclass correlation 15, with a design effect of 5.7, the total number will be at least 1900 patients across all districts, ie. approximately 120 people per district clinic.

For each randomisation unit, the number of inpatients will be between 100 and 400 people at any time. The expected DDDs per 1000 bed days was 81116. We expect the intervention will be associated with a reduction in the co-primary outcomes of: (a) reduction in DDD per 1000 bed-days of 25% 17 Assuming an intra-class correlation coefficient of up to 0.048, and an average number of inpatients of 150, we need 118 patients in total be able to detect a difference in DDD per 1000 bed-days of 25% ithout accounting for intraclass correlation. With a design effect of 5.7, the minimum sample size will be 672.
Therefore, the total number of people who will participate in the final survey at the end of the intervention period will be 1900.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
13/04/2022
Date of last participant enrolment
Anticipated
1/08/2022
Actual
13/10/2022
Date of last data collection
Anticipated
30/09/2022
Actual
15/12/2022
Sample size
Target
1900
Accrual to date
Final
4087
Recruitment outside Australia
Country [1] 24698 0
Viet Nam
State/province [1] 24698 0
Hanoi and Ca Mau provinces

Funding & Sponsors
Funding source category [1] 311130 0
Government body
Name [1] 311130 0
Department of Foreign Affairs and Trade (DFAT) Australia
Country [1] 311130 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Woolcock Institute of Medical Research Sydney
Address
431 Glebe Point Road
Glebe NSW 2037,
Australia
Country
Australia
Secondary sponsor category [1] 312472 0
Other Collaborative groups
Name [1] 312472 0
Woolcock Institute of Medical Research, Viet Nam
Address [1] 312472 0
Van Phuc Diplomatic Compound
298 Kim Ma
Ba Dinh district
Hanoi, Vietnam
Country [1] 312472 0
Viet Nam

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310659 0
University of Sydney
Ethics committee address [1] 310659 0
University of Sydney
Camperdown NSW 2006
Ethics committee country [1] 310659 0
Australia
Date submitted for ethics approval [1] 310659 0
17/01/2022
Approval date [1] 310659 0
24/03/2022
Ethics approval number [1] 310659 0
2022/034

Summary
Brief summary
This cluster randomised controlled trial aims to evaluate the effectiveness of a multi-faceted, Antimicrobial Stewardship (AMS) intervention on overall antibiotic use, and appropriate antibiotic use, in district health facilities. The unit of randomisation (cluster) is the district clinic. The intervention will be implemented by research staff in cooperation with healthcare workers in district facilities, pharmacists, academic and community partners.
The intervention will be delivered over a four-month period in the intervention group. After the intervention period the intervention will also be implemented in control sites. The co-primary outcomes will be measured before and after the intervention period. The co-primary outcomes are:
- The difference in the proportion of patients treated with appropriate antimicrobials according to a clinical audit of patient files, before and after the four-month intervention period, assessed using a locally-adapted version of the Australian National Antimicrobial Prescribing Survey (NAPS) tool, in the intervention group compared to the control arm.
- The difference in Defined Daily Doses (DDD) of antibiotics per 1,000 bed-days prescribed for inpatients, before and after the four-month intervention period, in the intervention group compared to the control arm.
Trial website
https://www.woolcockvietnam.org/vresist
Trial related presentations / publications
Public notes
This study is conducted in collaboration with the Australian National Antimicrobial Prescribing Service (NAPS).

Contacts
Principal investigator
Name 118426 0
Prof Gregory Fox
Address 118426 0
The University of Sydney
Rm 5216, Level 2 Medical Foundation Building K25
92-94 Parramatta Road | The University of Sydney | Camperdown | NSW | 2006


Country 118426 0
Australia
Phone 118426 0
+61290363121
Fax 118426 0
Email 118426 0
greg.fox@sydney.edu.au
Contact person for public queries
Name 118427 0
Prof Gregory Fox
Address 118427 0
The University of Sydney
Rm 5216, Level 2 Medical Foundation Building K25
92-94 Parramatta Road | The University of Sydney | Camperdown | NSW | 2006


Country 118427 0
Australia
Phone 118427 0
+61290363121
Fax 118427 0
Email 118427 0
greg.fox@sydney.edu.au
Contact person for scientific queries
Name 118428 0
Prof Gregory Fox
Address 118428 0
The University of Sydney
Rm 5216, Level 2 Medical Foundation Building K25
92-94 Parramatta Road | The University of Sydney | Camperdown | NSW | 2006


Country 118428 0
Australia
Phone 118428 0
+61290363121
Fax 118428 0
Email 118428 0
greg.fox@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
Results of audits will be available, however the detailed clinical data about patients is not collected due to confidentiality concerns.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
15638Ethical approval  greg.fox@sydney.edu.au Attachment below 383842-(Uploaded-27-04-2022-12-42-10)-Study-related document.pdf
15639Informed consent form  greg.fox@sydney.edu.au Attachment below 383842-(Uploaded-31-03-2022-14-49-58)-Study-related document.docx
15878Study protocol    383842-(Uploaded-08-05-2022-21-59-04)-Study-related document.docx



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Plain language summaryNo Analysed results are not yet ready

Documents added automatically
No additional documents have been identified.