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Trial registered on ANZCTR


Registration number
ACTRN12618000642280
Ethics application status
Approved
Date submitted
10/04/2018
Date registered
23/04/2018
Date last updated
16/01/2019
Date data sharing statement initially provided
16/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Combination Surgical Prophylaxis with Vancomycin versus Standard Prophylaxis for the Prevention of Surgical Site Infections following Elective and Expedited Surgery
Scientific title
Multicentre Randomised Double-Blind Placebo Controlled Trial of Combination Vancomycin versus Standard Surgical Antibiotic Prophylaxis
Secondary ID [1] 294561 0
Nil Known
Universal Trial Number (UTN)
U1111-1212-1900
Trial acronym
ASAP
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Surgical Antimicrobial Prophylaxis 307337 0
Antimicrobial Resistance 307338 0
Condition category
Condition code
Infection 306446 306446 0 0
Studies of infection and infectious agents
Surgery 306447 306447 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single dose intravenous vancomycin (1.5g) administered immediately prior to commencement of surgery. The vancomycin will be administered by the anaesthetist.

In addition to vancomycin, all participants will receive standard surgical antimicrobial prophylaxis with intravenous cefazolin (2g). The dose, timing and frequency of cefazolin is in keeping with national guidelines (Therapeutic Guidelines: Antibiotics) as part of standard care.
Intervention code [1] 300854 0
Prevention
Intervention code [2] 300889 0
Treatment: Drugs
Comparator / control treatment
Placebo will consist of 280mL of 0.9% saline (identical in appearance and volume to the vancomycin solution). The placebo will be administered immediately prior to commencement of surgery and will be administered by the anaesthetist.

All participants will receive standard surgical antimicrobial prophylaxis with intravenous cefazolin (2g). The dose, timing and frequency of cefazolin is in keeping with national guidelines (Therapeutic Guidelines: Antibiotics) as part of standard care.
Control group
Placebo

Outcomes
Primary outcome [1] 305457 0
The primary endpoint for this trial is a composite endpoint comprised of the incidence surgical site infections (superficial incisional, deep and organ/space SSI) defined according to modified CDC definitions.

Participants will be followed for 90 days for clinical outcomes

The processes for identifying outcomes will be conducted by the project research officer. Active surveillance for the primary outcome will comprise the following:
• Review of all participants’ medical records on discharge and follow-up at clinic
• Retrieval and review of records from other healthcare institutions as required
• Telephone contact for outcomes at 30 and 90 following index surgery
Timepoint [1] 305457 0
30 days and 90 days (primary endpoint) post index surgery
Secondary outcome [1] 345300 0
Incidence of superficial incisional SSI

The processes for identifying outcomes will be conducted by the project research officer. Active surveillance will comprise the following:
• Review of all participants’ medical records on discharge and follow-up at clinic
• Retrieval and review of records from other healthcare institutions as required
• Telephone contact for outcomes at 30 following index surgery
Timepoint [1] 345300 0
SSI outcomes will be assessed at 30 post index surgery
Secondary outcome [2] 345301 0
Composite incidence of SSI due to specific microorganism(s):
a. Staphylococcus aureus
i. Methicillin resistant
ii. Methicillin susceptible
b. Other Staphylococcus species
i. Methicillin resistant
ii. Methicillin susceptible
c. Enterococcus species
d. Other Gram-positive organisms
e. Gram-negative organisms and/or;
f. Fungi

The processes for identifying outcomes will be conducted by the project research officer. Active surveillance will comprise the following:
• Review of all participants’ medical records on discharge and follow-up at clinic
• Retrieval and review of records from other healthcare institutions as required
• Telephone contact for outcomes at 30, 90 and 180 following index surgery
Timepoint [2] 345301 0
SSI outcomes will be assessed at 30 and 90 days post index surgery
Secondary outcome [3] 345302 0
Composite incidence of other healthcare associated infections diagnosed according to the CDC definitions for healthcare associated infections:
a. Hospital acquired pneumonia
b. Urinary tract infections
c. Blood stream infections and;
d. Clostridium difficile infection

The processes for identifying outcomes will be conducted by the project research officer. Active surveillance will comprise the following:
• Review of all participants’ medical records on discharge and follow-up at clinic
• Retrieval and review of records from other healthcare institutions as required
Timepoint [3] 345302 0
At discharge from the acute health care admission for the index surgery
Secondary outcome [4] 345303 0
Incidence of late surgical site infections (infections occurring greater than 90 days after index surgery)

The processes for identifying outcomes will be conducted by the project research officer. Active surveillance will comprise the following:
• Review of all participants’ medical records on discharge and follow-up at clinic
• Retrieval and review of records from other healthcare institutions as required
• Telephone contact for outcomes at 180 following index surgery
Timepoint [4] 345303 0
Late SSI outcomes will be assessed at 180 days post index surgery
Secondary outcome [5] 345534 0
Microbiological sub-study: Incidence of SSI in participants colonised with Staphylococcus species at pre-admission screening.

The processes for identifying outcomes will be conducted by the project research officer. Active surveillance will comprise the following:
• Review of microbiological results for pre-admission swabs reviewed at 90 days post index surgery
Timepoint [5] 345534 0
SSI outcomes will be assessed at 90 days post index surgery
Secondary outcome [6] 345535 0
Composite Health economic analysis assessed with the following
• Quality of life scores, measured using the EQ-5D
• Healthcare utilisation costs
• Data linkage with MBS/PBS
Timepoint [6] 345535 0
180 days post index surgery
Secondary outcome [7] 345536 0
Adverse events / safety outcomes - Acute Kidney Injury
AKI is defined according to the modified 2012 KDIGO Clinical Practice Guideline for Acute Kidney Injury.
• Increase in Serum Creatinine by >=0.3 mg/dL (>=26.5 umol/L) within 48 hours of index surgery; or
• Increase in Serum Creatinine to >=1.5 times baseline, which is known or presumed to have occurred within the 7 days of index surgery; or
• Urine volume <0.5 mL/kg/h for 6 hours.
The processes for identifying outcomes will be conducted by the project research officer who will collect demographic data, results from serum urea, electrolytes and creatinine (UEC), full blood examination (FBE) and other laboratory testing. Active surveillance will comprise the following:
• Review of all participants’ medical records on discharge and follow-up at clinic
• Retrieval and review of records from other healthcare institutions as required
• Telephone contact for outcomes at 30 following index surgery
Timepoint [7] 345536 0
Assessed at 30 days post index surgery
Secondary outcome [8] 345537 0
Adverse Event / Safety Outcome - Adverse Drug reactions

• Hypersensitivity reactions including
a. Immediate (allergic) hypersensitivity
b. Delayed hypersensitivity
c. Immediate (non-allergic) hypersensitivity such as “Red Man Syndrome”

Active surveillance will comprise the following:
• Review of all participants’ medical records on discharge and follow-up at clinic
• Retrieval and review of records from other healthcare institutions as required
• Telephone contact for outcomes at 30 following index surgery
Timepoint [8] 345537 0
Assessed at 30 days post index surgery
Secondary outcome [9] 345538 0
All-cause mortality

Active surveillance will comprise the following:
• Review of all participants’ medical records on discharge and follow-up at clinic
• Retrieval and review of records from other healthcare institutions as required
• Telephone contact for outcomes at 30 and 90 days following index surgery
Timepoint [9] 345538 0
Assessed at 90 days post index surgery

Eligibility
Key inclusion criteria
Patients undergoing elective or expedited surgery
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Hypersensitivity to either cefazolin or glycopeptides (vancomycin and teicoplanin)
• Pregnancy and lactating women
• Surgery for suspected or proven surgical site infection
• Emergency or time critical surgery
- Arthroplasty for management of trauma / fracture including fractured neck of femur
- Arthroplasty for bone/soft tissue tumour
• Return to theatre / redo operation within index admission
• Documented or suspected infection or colonisation with MRSA

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)
Randomisation of participants to treatment arms will be as a password-protected, secure website using a central, computer-based randomisation program. Participants, treating clinicians, all members of the research team including the study statistician will be blinded to treatment arm allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation of participants to treatment arms will be as a password-protected, secure website using a central, computer-based randomisation program with permutated blocks and allocation of participants stratified according to the centre and by procedure.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
N/A
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The primary analysis will be on an intention-to-treat basis where patients will be analysed in their originally allocated treatments. As a large randomized controlled trial, covariate balance is expected. The primary outcome will be compared between the two groups through calculation of the relative risk (RR) and risk difference (RD). A test of interaction will be used to assess for sub-group effects.

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,VIC
Recruitment hospital [1] 10616 0
Epworth Richmond - Richmond
Recruitment hospital [2] 10617 0
Latrobe Regional Hospital - Traralgon
Recruitment hospital [3] 10618 0
The Sutherland Hospital - Caringbah
Recruitment hospital [4] 10619 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [5] 10620 0
St Andrew's War Memorial Hospital - Brisbane
Recruitment hospital [6] 10621 0
The Prince Charles Hospital - Chermside
Recruitment hospital [7] 12915 0
Bendigo Health Care Group - Bendigo Hospital - Bendigo
Recruitment hospital [8] 12916 0
St George Private Hospital - Kogarah
Recruitment hospital [9] 12917 0
Prince of Wales Private Hospital - Randwick
Recruitment hospital [10] 12918 0
Prince of Wales Hospital - Randwick
Recruitment hospital [11] 12919 0
Brisbane Private Hospital - Brisbane
Recruitment postcode(s) [1] 22333 0
3121 - Richmond
Recruitment postcode(s) [2] 22334 0
3844 - Traralgon
Recruitment postcode(s) [3] 22335 0
2229 - Caringbah
Recruitment postcode(s) [4] 22336 0
3065 - Fitzroy
Recruitment postcode(s) [5] 22337 0
4000 - Brisbane
Recruitment postcode(s) [6] 22338 0
4032 - Chermside
Recruitment postcode(s) [7] 25392 0
3550 - Bendigo
Recruitment postcode(s) [8] 25393 0
2217 - Kogarah
Recruitment postcode(s) [9] 25394 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 299181 0
Government body
Name [1] 299181 0
National Health and Medical Research Council
Address [1] 299181 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 299181 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Scenic Blvd, Clayton VIC 3800
Country
Australia
Secondary sponsor category [1] 298444 0
None
Name [1] 298444 0
Address [1] 298444 0
Country [1] 298444 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300105 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 300105 0
Alfred Hospital
Commercial Road, Melbourne VIC 3004
Ethics committee country [1] 300105 0
Australia
Date submitted for ethics approval [1] 300105 0
06/06/2018
Approval date [1] 300105 0
09/07/2018
Ethics approval number [1] 300105 0
HREC/18/Alfred/102

Summary
Brief summary
This randomised, double-blind, placebo-controlled, phase 4 trial will compare the incidence of surgical site infection, safety and cost-effectiveness of surgical prophylaxis with cefazolin plus vancomycin to cefazolin plus placebo. The study will be initially undertaken in patients undergoing elective or expedited joint replacement surgery. Dependent on timelines and funding, the study may be expanded to include patients undergoing cardiac surgery.
Trial website
asaptrial.org.au
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82582 0
Dr Trisha Peel
Address 82582 0
Department of Infectious Diseases
Monash University and Alfred Health
85 Commercial Road
Melbourne, VIC 3004
Country 82582 0
Australia
Phone 82582 0
+61 3 9076 2000
Fax 82582 0
+61 3 9076 2431
Email 82582 0
Trisha.Peel@monash.edu
Contact person for public queries
Name 82583 0
Dr Trisha Peel
Address 82583 0
Department of Infectious Diseases
Monash University and Alfred Health
85 Commercial Road
Melbourne, VIC 3004
Country 82583 0
Australia
Phone 82583 0
+61 3 9076 2000
Fax 82583 0
+61 3 9076 2431
Email 82583 0
Trisha.Peel@monash.edu
Contact person for scientific queries
Name 82584 0
Dr Trisha Peel
Address 82584 0
Department of Infectious Diseases
Monash University and Alfred Health
85 Commercial Road
Melbourne, VIC 3004
Country 82584 0
Australia
Phone 82584 0
+61 3 9076 2000
Fax 82584 0
+61 3 9076 2431
Email 82584 0
Trisha.Peel@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The datasets used and/or analysed during the current study may be available from the corresponding author on reasonable request.
What supporting documents are/will be available?
No other documents available
Summary results
Not applicable