Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001655831p
Ethics application status
Submitted, not yet approved
Date submitted
19/10/2021
Date registered
1/12/2021
Date last updated
1/12/2021
Date data sharing statement initially provided
1/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Topical Antibiotics in Ankle Fracture Surgery (TAAFS) pilot study
Scientific title
The effect of Topical Antibiotics in Ankle Fracture Surgery (TAAFS) on the rate of surgical site infections: a pilot study
Secondary ID [1] 305584 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Topical Antibiotics in Ankle Fracture Surgery (TAAFS)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ankle fracture
 324004 0
surgical site infection 324005 0
Condition category
Condition code
Surgery 321511 321511 0 0
Surgical techniques
Musculoskeletal 321689 321689 0 0
Other muscular and skeletal disorders
Infection 321690 321690 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
To evaluate whether the addition of topical antibiotics (vancomycin and gentamicin) at the time of wound closure reduces surgical site infection in ankle fracture surgery.
Patients randomized to the intervention arm will receive local antibiotics. The first of these two groups will receive 1000 mg of sterile vancomycin powder mixed with 160 mg gentamicin liquid (80mg per 2mls solution), forming a 4ml antibiotic solution. The scrub nurse mixes the 1000 mg of powdered vancomycin with the 160 mg gentamicin liquid (formulation comes as 80 mg/2ml). This makes a 4 ml clear thickened fluid which is then drawn up into a 5ml syringe. A 25g needle is then applied to the syringe, and the antibiotic solution can then be directly applied into the wound following fixation and final saline irrigation, but prior to wound closure. If multiple wounds are present, as in the case of bi/tri-malleolar fracture fixation, then the solution will be divided between the wounds in proportions equal to the relative wound sizes as per the surgeon’s clinical judgement. The solution will not be used for percutaneous single screw or reduction clamp incisions. Surgeons are to place the solution directly into the deep portion of the wound onto exposed metalwork, and are not to alter the solution in any way prior to its application.

Duration of the surgical procedure will vary and depend on fracture type, complexity and surgeon operative speed. Typically ankle fracture surgery takes between 45min and 2hrs.

The surgical wound is closed in a standard fashion and will be at the discretion of the surgeon. Wound closure should be in layers and aim to be watertight, with deeper layers being closed typically with absorbable 1-0/2-0/3-0 Vicryl, PDS, or Monocryl. Skin is usually closed with either 3-0/4-0 nylon, Prolene, or Monocryl.

Intervention code [1] 321984 0
Treatment: Drugs
Intervention code [2] 322118 0
Prevention
Comparator / control treatment
Participants randomized to the control group will receive accepted standard of care treatment and will not receive any local antibiotic therapy on wound closure. The treating surgeon will instead spray 4ml of normal saline from a 5ml syringe using a 25g needle. The instillation of the saline into the wound will occur in identical fashion as to the intervention group. The surgical team will be blinded as to which preparation they are instilling into the wound, and the normal saline will serve as the placebo arm.

Duration of the surgical procedure will vary and depend on fracture type, complexity and surgeon operative speed. Typically ankle fracture surgery takes between 45min and 2hrs.

The surgical wound is closed in a standard fashion and will be at the discretion of the surgeon. Wound closure should be in layers and aim to be watertight, with deeper layers being closed typically with absorbable 1-0/2-0/3-0 Vicryl, PDS, or Monocryl. Skin is usually closed with either 3-0/4-0 nylon, Prolene, or Monocryl.
Control group
Placebo

Outcomes
Primary outcome [1] 329280 0
Prevalence of deep surgical site infection (SSI) as defined by centre for disease control and prevention (CDC) guidelines for deep surgical site infection
Timepoint [1] 329280 0
Patients will be assessed for SSI at 2 weeks, 6 weeks, 3 months, 6 months and 12 months post surgery.
Primary outcome [2] 329454 0
Prevalence of deep surgical site infection (SSI) according to the Fracture Related Infection Consensus Classification
Timepoint [2] 329454 0
Patients will be assessed for SSI at 2 weeks, 6 weeks, 3 months, 6 months and 12 months post surgery.
Primary outcome [3] 329455 0
Prevalence of superficial surgical site infection (SSI) as defined by centre for disease control and prevention (CDC) guidelines for superficial surgical site infection.
Timepoint [3] 329455 0
Patients will be assessed for SSI at 2 weeks, 6 weeks, 3 months, 6 months and 12 months post surgery.
Secondary outcome [1] 402674 0
Pain using a visual analogue score (VAS)
Timepoint [1] 402674 0
VAS will be assessed at 2 weeks, 6 weeks, 3, 6 and 12 months post surgery
Secondary outcome [2] 403346 0
Ankle function using the A-Form
Timepoint [2] 403346 0
A-Form will be assessed at 3, 6 and 12 months post surgery
Secondary outcome [3] 403347 0
Ankle function using the Foot and Ankle Outcome Score (FAOS)
Timepoint [3] 403347 0
FAOS will be assessed at 3, 6 and 12 months post surgery
Secondary outcome [4] 403348 0
Quality of life using the EQ-5D-5L
Timepoint [4] 403348 0
EQ-5D-5L will be assessed at 3, 6 and 12 months post surgery

Eligibility
Key inclusion criteria
Patients aged 18 and older
Injury meeting the following criteria:
a. Open or Closed Ankle Fracture
b. Definitively treated with plate and screw fixation
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Patients with fractures that have evidence of active infection (fracture related infection) or have evidence of systemic infection or sepsis (chest infection, urinary traction infection or similar) or other unrelated orthopaedic infection such as a prosthetic joint or chronic musculoskeletal infection for which they are currently on treatment for
• Patients with adjacent fractures to the same limb – tibia pilon, tibial shaft, talus, or mid foot fractures requiring operative intervention
• Patients with bilateral ankle injuries due to the risk of systemic antibiotic toxicity from dual dosage and confounding of placebo results
• Patients with a subsequent injury who have previously been enrolled in the study for the contralateral limb
• Patients with periprosthetic ankle fractures with existing orthopaedic implants
• Patients with open G3 Gustilo-Anderson injuries who will not undergo primary coverage or closure at the time of fixation and will have such treatment scheduled for a subsequent procedure date
• Patients who have already had definitive fixation before enrollment in the trial
• Patients with an allergy or history of adverse drug reaction to vancomycin
• Patient with an allergy or history of adverse drug reaction to gentamicin
• Patients who are currently pregnant
• Patients who are do not speak English
• Patients who are incarcerated
• Patients who are determined by the local investigators to have severe difficulties in maintaining follow-up for the following reasons:
o Diagnosis of a severe psychiatric disorder that is not adequately controlled
o Patients without capacity or lack family support to participate in follow-up
o Patients living remote from the study site who are unable to be followed up at any of the study sites
o Patients who are homeless without adequate contact information to facilitate follow-up

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)
allocation by sealed envelope
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
block randomisation 1:1 ratio
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
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size has been calculated using an alpha value of 0.05 and power of 0.8, to determine a 50% reduction in the incidence of deep SSIs in the treatment arm. It is presumed that the incidence of deep SSI will be 6% based on existing population studies. A 1:1 enrolment ratio will be employed. A 10% loss to follow-up is expected due to current trends and the population profile. The calculated sample size is thus 1496 without any loss to follow up, and 1662 with expected losses. The pilot study will consist of a sample size of 20% of the full study, consisting of 332 patients

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
31/01/2022
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
332
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 20799 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [2] 20800 0
The Townsville Hospital - Douglas
Recruitment hospital [3] 20801 0
Cairns Base Hospital - Cairns
Recruitment postcode(s) [1] 35616 0
4029 - Herston
Recruitment postcode(s) [2] 35617 0
4814 - Douglas
Recruitment postcode(s) [3] 35618 0
4870 - Cairns

Funding & Sponsors
Funding source category [1] 309948 0
Charities/Societies/Foundations
Name [1] 309948 0
Queensland Orthopaedic Research Fund (QORF)
Country [1] 309948 0
Australia
Primary sponsor type
Individual
Name
Dr William O'Callaghan
Address
Department of Orthopaedics
Cairns Hospital
165 Esplanade, Cairns, QLD 4870
Country
Australia
Secondary sponsor category [1] 311142 0
None
Name [1] 311142 0
none
Address [1] 311142 0
none
Country [1] 311142 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 309663 0
The Royal Brisbane & Women's Research Ethics Committee (HREC)
Ethics committee address [1] 309663 0
Human Research Ethics Office
Level 2, Building 34
Butterfield Street
HERSTON QLD 4029
Ethics committee country [1] 309663 0
Australia
Date submitted for ethics approval [1] 309663 0
25/10/2021
Approval date [1] 309663 0
Ethics approval number [1] 309663 0

Summary
Brief summary
The proposed pilot study is a multi-center, prospective, double-blinded, randomized controlled trial comparing standard surgical fixation of ankle fractures with and without local topical antibiotics at the time of wound closure. The null hypothesis is that there will be no difference in post-operative rates of infection despite the addition of local topical antibiotics to the surgical wound at the time of closure. We will test our hypothesis by randomizing one group of patients to receive topical vancomycin and gentamicin solution to the wound at the time of closure and the other group to not receive additional topical antibiotics. Routine follow-up of patients will be completed under the standard of care, to assess whether or not the addition of topical antibiotics at the time of wound closure will reduce the rate of post-operative wound infection in ankle fracture surgery.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 114954 0
Dr William O'Callaghan
Address 114954 0
Orthopaedic Surgeon
Cairns Hospital, 165 The Esplanade
Cairns, QLD 4870
Country 114954 0
Australia
Phone 114954 0
+61 421778329
Fax 114954 0
Email 114954 0
william.b.ocallaghan@gmail.com
Contact person for public queries
Name 114955 0
Dr William O'Callaghan
Address 114955 0
Orthopaedic Surgeon
Cairns Hospital, 165 The Esplanade
Cairns, QLD 4870
Country 114955 0
Australia
Phone 114955 0
+61 742260000
Fax 114955 0
Email 114955 0
william.b.ocallaghan@gmail.com
Contact person for scientific queries
Name 114956 0
Dr William O'Callaghan
Address 114956 0
Orthopaedic Surgeon
Cairns Hospital, 165 The Esplanade
Cairns, QLD 4870
Country 114956 0
Australia
Phone 114956 0
+61 421778329
Fax 114956 0
Email 114956 0
william.b.ocallaghan@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified patient data including individual participant data pertaining to published results only.
When will data be available (start and end dates)?
At trial completion following analysis and will be available for 7 years following publication.
Available to whom?
On written request by other researchers with a methodologically sound proposal.
Available for what types of analyses?
meta analysis
How or where can data be obtained?
From Queensland Health repository after contacting authors
william.b.ocallaghan@gmail.com
ktetsworthmd@gmail.com


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.