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Trial registered on ANZCTR


Registration number
ACTRN12620001295932
Ethics application status
Approved
Date submitted
1/10/2020
Date registered
30/11/2020
Date last updated
22/08/2022
Date data sharing statement initially provided
30/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Streamlining antibiotic allergy testing for elective surgery patients using smartphone based apps
Scientific title
PeRiopErative Penicillin/Cephalosporin AlleRgy TEsting - A phase II feasibility/safety randomised control trial to empower anaesthetists to risk stratify and de-label antibiotic allergy labels in the perioperative period using digital health solutions.
Secondary ID [1] 302281 0
Nil Known
Universal Trial Number (UTN)
U1111-1258-1711
Trial acronym
PREPARE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Penicillin Allergy 319025 0
Cephalosporin Allergy 319026 0
Antibiotic Allergy 319027 0
Condition category
Condition code
Inflammatory and Immune System 316981 316981 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pre-operative risk stratification and de-labelling of antibiotic allergy labels:

Aim: Develop and implement a point of care, smartphone app based beta-lactam allergy de-labelling tool in perioperative medicine and assess the safety and feasibility of this intervention.

Materials:
Risk stratification of antibiotic allergy labels via a custom built smartphone app, based on a validated assessment tool. To be used by anaesthetists during pre-operative assessment.

Procedure:
Participants in pre-operative assessment clinic (PAC) with penicillin or cephalosporin allergy will be randomised to either the intervention arm or control arm. Those randomised to intervention arm will go on to be risk-stratified. Risk stratification is carried out by clinical staff within the PAC during a routine 20min consultation via the use of a smartphone application containing the validated Antibiotic Allergy Assessment Tool. Pre-operative assessment occurs between 1 week and 1 day prior to surgery.

Participants identified as having a 'low-risk' penicillin or cephalosporin allergy label will go on to be challenged with an oral dose of penicillin VK, amoxicillin or cefalexin and observed for 1 hour post. This challenge occurs on the same day, directly after risk stratification occurs.

Delivered by who and where:
Risk-stratification will be completed by anaesthetic specialist in pre-operative assessment outpatient clinic. Participants who go on to challenge will also be challenged with a dose of antibiotic and observed within the same outpatient clinic.
Intervention code [1] 318569 0
Treatment: Other
Comparator / control treatment
Participants randomised to the control arm will go on to receive standard of care and will be referred for allergy testing via the normal hospital based pathways. Standard of care in this context includes use of alternative antibiotics on the day of surgery and/or referral for further allergy testing post-surgery. This referral occurs on discharge from hospital.
Control group
Active

Outcomes
Primary outcome [1] 325089 0
Feasibility of recruitment/intervention delivery:
a) Feasibility of intervention delivery defined as the proportion of patients randomised to the intervention arm who had the intervention delivered as per protocol
- Determined by audit of clinical notes
b) Feasibility of recruitment defined as the proportion of patients consenting to participation in the study as per protocol from eligible patients.
- Determined by audit of clinical notes
Timepoint [1] 325089 0
On the day of pre-operative assessment
Primary outcome [2] 325090 0
Safety:
a) The proportion of patients with a penicillin allergy who experience an antibiotic associated adverse event and/or severe adverse drug reaction.
- Occurrence of adverse events will be determined from medical records
Timepoint [2] 325090 0
Assessed at two main time points:
a) On the day of pre-operative assessment and/or challenge
b) At the time of surgery and in the post-surgical period
Secondary outcome [1] 386823 0
Beta-lactam utilization in perioperative period (n, %). This would be assessed by examining patient medical records.
Timepoint [1] 386823 0
At time of surgery (up to 72 hours post surgery)
Secondary outcome [2] 386824 0
Surgical operating times (minutes). This would be assessed by examining patient medical records.
Timepoint [2] 386824 0
At time of surgery
Secondary outcome [3] 386825 0
Proportion of patients (n, %) with a beta-lactam allergy that develop a surgical site infection up to 90 days post surgery.
Timepoint [3] 386825 0
Assessed at 30 days and 90 days post surgery.
Secondary outcome [4] 388431 0
Proportion of patients with a beta-lactam allergy that utilize any beta-lactam in surgical prophylaxis. This will be assessed via telephone follow up at 30 and 90 days.
Timepoint [4] 388431 0
Assessed at time of surgery, with surgical prophylaxis defined as antibiotic given 30min to 1hr prior to surgical incision.
Secondary outcome [5] 413210 0
Proportion of patients with a beta-lactam allergy that develop an acute kidney injury in the 72 hours post surgery. This will be collected via data-linkage to medical records.
Timepoint [5] 413210 0
Assessed within 72hours after surgery, done by chart review.
Secondary outcome [6] 413211 0
Median time from antibiotic administration to surgical incision (mins). This will be collected via data-linkage to medical records.
Timepoint [6] 413211 0
Assessed at time of surgery
Secondary outcome [7] 413212 0
Proportion of patients with a beta-lactam allergy with a non-elective admission to the ICU unit in the 72 hours post surgery. This will be collected via data-linkage to medical records.
Timepoint [7] 413212 0
Assessed within preoperative period up to 72hours post surgery
Secondary outcome [8] 413213 0
Median length-of-stay. This will be collected via data-linkage to medical records.
Timepoint [8] 413213 0
On discharge from hospital, identified via chart review at the 30 day post-surgical time point
Secondary outcome [9] 413214 0
Inpatient mortality. This will be collected via data-linkage to medical records.
Timepoint [9] 413214 0
Defined as death during inpatient stay post surgery.
Secondary outcome [10] 413215 0
Proportion of patients with a beta-lactam allergy that utilize an appropriate antibiotic for surgical prophylaxis (defined by NAPs definitions). This will be collected via data-linkage to medical records.
Timepoint [10] 413215 0
Assessed at time of surgery, with surgical prophylaxis defined as antibiotic given 30min to 1hr prior to surgical incision.
Secondary outcome [11] 413216 0
Proportion of patients with a beta-lactam allergy that utilize an appropriate antibiotic in the perioperative period (72 hours post surgery) [defined by NAPs definitions]. This will be collected via data-linkage to medical records.
Timepoint [11] 413216 0
At time of surgery, up to 72hours post surgery.

Eligibility
Key inclusion criteria
Patients aged 18 years and above that are reviewed in the perioperative assessment clinic under the care of a surgerical unit, having a reported penicillin or cephalosporin allergy label, and will require intravenous antibiotic therapy in planned perioperative care.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Inpatients
Patients aged < 18 years
Patients currently receiving beta-lactam antibiotic therapy
Previous referral or assessment by a specialist for beta-lactam allergy
Under the current care of an Allergy/Immunology specialist
Require non-beta-lactam antibiotics for an infection or colonization with an organism resistant to beta-lactam (eg MRSA, ESBL producing gram negatives)
Emergency or trauma surgery
Contraindication for oral penicillin provocation
• Patients receiving more than 10mg of prednisolone or
equivalent daily
• Patients receiving antihistamine therapies
• Patients with a history of drug-associated anaphylaxis or idiopathic urticaria/anaphylaxis

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation via computer program
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?

The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis
The sample size calculations for this feasibility and safety study is based on the precision of
the estimates for the feasibility outcomes.

Feasibility considerations: We would like to be able to estimate the proportion of patients
randomized in the intervention arm to actually receive the intervention as per protocol with
sufficient precision. Recruiting 49 patients in the intervention arm of the study would provide
the precision (half-width of the 95% confidence interval) of 8% to estimate the underlying
proportion of patients treated per protocol to be 85% as per the definition provided earlier in
this protocol.

Safety considerations: We would like to be able to estimate the proportion of patients
experiencing adverse events casually related to the study in the intervention arm with sufficient precision. Recruiting 73 patients in the intervention arm of the study would provide the precision (half-width of the 95% confidence interval) of 5% to estimate the underlying proportion of patients experiencing any adverse event (See - serious adverse event or antibiotic associated adverse event definitions) to the study to be 5%.

Assuming 1:1 randomization between two study arms, we would randomize 150 patients
(sample size calculation to assessed safety requires 73 in each arm [146 total], total
randomized rounded to 150 total). in total, providing sufficient precision for both feasibility and
safety outcomes.

This sample size is feasible, as we assume that 9% of all screened patients will report a
penicillin allergy as per national data, thus requiring us to screen up to 1750 patients. This
will be achieved by 4 centres each contributing approximately 40 patients out of their general
480 patient per year cohort.

Feasibility of intervention delivery and feasibility of recruitment will be reported as proportions
with respective 95% confidence intervals. The proportions of patients with a penicillin allergy
who experience an antibiotic associated adverse event and/or severe adverse drug reaction
as per protocol definitions will be reported by group with respective 95% confidence intervals
and compared using modified Poisson regression model with robust standard error estimation. Corresponding effect size will be reported as risk ratio with respective 95% confidence interval.

Secondary outcomes will be reported by group and compared using appropriate regression
models. Details of statistical analysis will be documented in a separate Statistical Analysis
Plan (SAP) that will be developed and finalized prior to the study database lock.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
14/12/2020
Actual
4/02/2021
Date of last participant enrolment
Anticipated
31/01/2023
Actual
Date of last data collection
Anticipated
31/03/2023
Actual
Sample size
Target
150
Accrual to date
39
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 17503 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 17504 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [3] 17505 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 31232 0
3050 - Parkville
Recruitment postcode(s) [2] 31233 0
3084 - Heidelberg
Recruitment postcode(s) [3] 31234 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 306708 0
Commercial sector/Industry
Name [1] 306708 0
MERCK SHARP & DOHME
Country [1] 306708 0
Australia
Primary sponsor type
Hospital
Name
Austin Health
Address
145 Studley Rd
Heidelberg VIC 3084
Country
Australia
Secondary sponsor category [1] 307438 0
None
Name [1] 307438 0
Address [1] 307438 0
Country [1] 307438 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306878 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 306878 0
Ethics committee country [1] 306878 0
Australia
Date submitted for ethics approval [1] 306878 0
24/04/2018
Approval date [1] 306878 0
28/01/2020
Ethics approval number [1] 306878 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105318 0
A/Prof Jason Trubiano
Address 105318 0
Department of Infectious Diseases
Austin Health
145 Studley Rd
Heidelberg VIC 3084
Country 105318 0
Australia
Phone 105318 0
+61394966676
Fax 105318 0
Email 105318 0
jason.trubiano@austin.org.au
Contact person for public queries
Name 105319 0
Joseph De luca
Address 105319 0
Department of Infectious Diseases
Austin Health
145 Studley Rd
Heidelberg VIC 3084
Country 105319 0
Australia
Phone 105319 0
+61394966676
Fax 105319 0
Email 105319 0
joseph.deluca@austin.org.au
Contact person for scientific queries
Name 105320 0
Joseph De luca
Address 105320 0
Department of Infectious Diseases
Austin Health
145 Studley Rd
Heidelberg VIC 3084
Country 105320 0
Australia
Phone 105320 0
+61394966676
Fax 105320 0
Email 105320 0
joseph.deluca@austin.org.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 Supporting Document Provided


Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIStudy protocol for PREPARE: a phase II feasibility/safety randomised controlled trial on PeRiopErative Penicillin AlleRgy TEsting2023https://doi.org/10.1136/bmjopen-2022-067653
N.B. These documents automatically identified may not have been verified by the study sponsor.