Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001318875
Ethics application status
Approved
Date submitted
15/07/2021
Date registered
28/09/2021
Date last updated
28/09/2021
Date data sharing statement initially provided
28/09/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Penicillin Allergy De-Labelling in Paediatric OutPatients (PADLPOP) study
Scientific title
Efficacy of a penicillin allergy de-labelling service in a paediatric outpatient setting
Secondary ID [1] 304732 0
nil
Universal Trial Number (UTN)
Trial acronym
PADLPOP study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Penicillin allergy 322753 0
Condition category
Condition code
Inflammatory and Immune System 320343 320343 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A patient with a penicillin allergy label will have a clinical assessment with a paediatrician to determine their risk of a true allergic reaction. The assessment will be completed via the administration of a questionnaire. The clinical assessment will be conducted via Telehealth or in person in the clinic rooms. It will take approximately 20 minutes. The assessment of risk and recommendations for ongoing management will be made in accordance with the Australian Society for Clinical Immunology and Allergy (ASCIA) 'Consensus statement for the assessment of patients with suspected penicillin allergy'.

Patients determined to be at no risk of a true allergic reaction will be "de-labelled" i.e. have their penicillin allergy label removed without further testing.

Patients determined to be at low risk of a true penicillin allergy will be offered an oral provocation challenge in the emergency department.

Patients determined to be at high risk of a true penicillin allergy will remain labelled as allergic. They will not be offered an oral provocation challenge and they will not be included in the outcome assessments described below.

All patients will receive documentation (obtained from the Australian Society for Clinical Immunology and Allergy (ASCIA) website) verifying their allergy status (confirmed allergic or confirmed NOT allergic).

Oral provocation challenges will be performed as a 2-stage oral provocation challenge in the emergency department. The antibiotic will be given as an oral suspension (liquid). The patient will be given 10% of the dose followed by the remaining 90% of the dose. In cases of unspecified ‘penicillin’ allergy the patient will be challenged against amoxicillin (a commonly used penicillin-antibiotic in the community).

Doses for antibiotics:
• Amoxicillin 15mg/kg (max 500mg)
• Phenoxymethylpenicillin 10mg/kg (max 500mg)
• Amoxicillin/clavulanic acid 22.5mg/kg (max 875 mg)
• Flucloxacillin 12.5mg/kg (max 500mg)

After receiving 10% of the dose, patients will be observed for 30 minutes for signs or symptoms of a reaction. If there are no signs or symptoms of a reaction then the remaining 90% of the dose should be given and the patient observed for a further 60 minutes. If the patient does not have an allergic reaction they will be given a 5 day course of the culprit/testing antibiotic to take home. This is to assess for delayed reactions. The patient receives 1 full dose in the emergency department. The 5 day course commences with the dose received in the emergency department.

Doses for take home antibiotics:
• Amoxicillin 15mg/kg twice daily (max 500mg)
• Phenoxymethylpenicillin 10mg/kg twice daily (max 500mg)
• Amoxicillin/clavulanic acid 22.5mg/kg twice daily (max 875 mg)
• Flucloxacillin 12.5mg/kg twice daily (max 500mg)

Take home antibiotics will be provided as oral suspensions (liquid) or a capsule if appropriate.

Patients are asked to keep a diary to monitor adherence, side effects and reactions. Patients will also be called by the research nurse on approximately day 6-10. If the patient completes the 5 days course without having a delayed allergic reaction they will be "de-labelled" i.e. have their allergy label removed.

After the patients allergy status has been confirmed they will be followed up for 12 months with telephone calls at 4, 8 and 12 months. A research team member will follow subjects to assess measurable clinical outcomes: utilisation of antibiotics in the community, type and cause of infections in the community, GP and other primary care provider visits, change in prescription patterns, presentation to ED, referrals and attendance at Immunology/Allergy clinic and details about hospital admissions.
Intervention code [1] 321107 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328512 0
Efficacy of an oral provocation challenge in children with ‘low’ risk histories for penicillin allergy will be assessed by the proportion of children who have their allergies verified after the provocation challenge. These data will be recorded by clinician review of participants during the first challenge visit and review of patient diaries after a 5 day at-home challenge
Timepoint [1] 328512 0
Allergy status verification will be assessed at the time of the first oral provocation challenge, at 6-10 days after the first challenge, and then at 4, 8 and 12 months after the first challenge
Primary outcome [2] 328981 0
Efficacy of direct de-labelling in children with ‘no’ risk histories for penicillin allergy will be assessed by the proportion of children who have their allergies status verified after clinical review by the paediatrician at the clinic visit.
Timepoint [2] 328981 0
Allergy status verification will occur after the clinical review by the paediatrician at the clinic visit and then at 4, 8 and 12 months after the first challenge
Secondary outcome [1] 398181 0
Cost-effectiveness of the service

A trial-based cost-consequence analysis will be conducted. This will involve collection of resource use costs and effectiveness outcomes. The resource use data will primarily include the cost of labour and materials. The labour cost will be estimated using award level, task type and duration. The cost of materials and equipment will be estimated using market prices. In the process of oral amoxicillin challenge, should the patient require active management of an adverse reaction, measurement of costs will be based on the labour involved in managing the adverse reaction and any medications used. Effectiveness outcomes include the proportion of patients de-labelled (after oral challenge) and the subsequent change in antibiotic use. The outcomes regarding antibiotic use (post allergy testing) will be collected using patient diaries. All costs and outcomes will be prospectively collected by the researcher as part of the study and will be reported on a per patient basis. Sensitivity and uncertainty analyses (around the cost and effectiveness estimates) will be undertaken to assess the robustness of the results.
Timepoint [1] 398181 0
12 months post intervention completion
Secondary outcome [2] 399591 0
Safety of de-labelling patients at no risk or low risk of a true penicillin allergy in the out-patient setting. An adverse event is defined as a mild to moderate allergic reaction. A serious adverse event is defined as a severe/anaphylactic reaction. Definitions are in accordance with the Australian Society for Clinical Immunology and Allergy documentation.
Timepoint [2] 399591 0
The safety of the intervention will be determined at 2 time points.
1) After 60 minutes continuous monitoring post administration of the 90% dose of penicillin in the emergency department.
2) At the follow-up phone call on day 6-10 post completion of the 2-stage oral provocation challenge in the Emergency Department. Day 1 is the day of the oral provocation challenge. At home monitoring involves the patient completing a patient diary and contacting the research team or Pindara Emergency Department if they develop symptoms.

Eligibility
Key inclusion criteria
• Parent reported allergy to penicillin
• Age 1-16 years
• Parent or legal guardian able to provide informed consent
Minimum age
1 Years
Maximum age
16 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• History consistent with a ‘high risk’ of a penicillin allergy (rash within the last year, or angioedema and/or systemic symptoms or unknown history)
• Pregnancy
• Significant immunosuppression due to medical treatment including daily oral steroids exceeding a dose of 0.5mg/kg
• Any unstable medical condition which in the opinion of the investigator will place them at increased risk should a serious adverse event occur e.g. poorly controlled asthma or heart failure

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



Intervention assignment
Other
Other design features
-Patients will have their risk of having a true penicillin allergy assessed. The patient's management will be based on the risk assessment.
-Patients at 'no risk' (e.g. avoiding penicillins because of a family history) will have their allergy label removed i.e., be "de-labelled"directly without further testing.
-Patients at 'low risk' of a true penicillin allergy will be offered an oral provocation challenge in the Emergency Department.
-Patients at 'high risk' of a true penicillin allergy will remain labelled as allergic. The assessment of high risk patients should ONLY occur through specialist allergy services, which are currently unavailable through the public system.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This is an pragmatic implementation study. The primary endpoint will be evaluated by the number of children that have been de-labelled by the intervention. Initially, differences between those that are de-labelled and the appropriate age range, population level data of antibiotic utilisation in the community, type and cause of infections, GP and other primary care provider visits, presentations to ED, hospital admissions and infection rates will be assessed using chi-squared tests.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
25/10/2021
Actual
Date of last participant enrolment
Anticipated
24/10/2022
Actual
Date of last data collection
Anticipated
20/11/2023
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 19959 0
Pindara Private Hospital - Benowa
Recruitment postcode(s) [1] 34666 0
4217 - Benowa

Funding & Sponsors
Funding source category [1] 309105 0
Charities/Societies/Foundations
Name [1] 309105 0
Ramsay Hospital Research Foundation
Country [1] 309105 0
Australia
Primary sponsor type
Individual
Name
Dr Amy Whittaker
Address
Leading Steps Paediatric Clinic
Pindara Specialists Suites (Benowa)
Suite 4.05, Pindara Specialist Suites,
29 Carrara Street, Benowa QLD 4217
Country
Australia
Secondary sponsor category [1] 310386 0
None
Name [1] 310386 0
Address [1] 310386 0
Country [1] 310386 0
Other collaborator category [1] 281940 0
Other
Name [1] 281940 0
Clinical trials unit at Pindara Private Hospital
Address [1] 281940 0
Pindara Private Hospital
Allchurch Avenue
BENOWA QLD 4217
Country [1] 281940 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308973 0
Greenslopes Research and Ethics Committee
Ethics committee address [1] 308973 0
Greenslopes Private Hospital
Newdegate Street
Greenslopes QLD 4120
Ethics committee country [1] 308973 0
Australia
Date submitted for ethics approval [1] 308973 0
19/07/2021
Approval date [1] 308973 0
24/08/2021
Ethics approval number [1] 308973 0
21/06

Summary
Brief summary
Penicillin allergy labels are common and are associated with adverse outcomes. It is widely recommended that people with a penicillin allergy label have an assessment to check if they are truly allergic. However, access to penicillin allergy assessment services is currently very limited.

This study will assesses the implementation of the ASCIA (Australian Society for Clinical Immunology and Allergy) 'Consensus statement for the assessment of patients with suspected penicillin allergies' in a real-world health care system. The study aims to identify children with a penicillin allergy label who are at no or low risk of a true penicillin allergy, arrange for them to undertake an assessment and de-label those with inappropriate penicillin allergies. The study aims to demonstrate that this model of care is safe, effective and is associated with health-economic benefits.

It is hypothesised that children who are eligible for the study can be can be safely assessed and have have their allergy status verified in a community based private health service with no costs to the patient. It is hypothesised that the majority of patients will have their penicillin allergy label removed.

Patients are assessed via the administration of a questionnaire and oral provocation challenge, if indicated. During an oral provocation challenge the patient takes a small and then larger amount of the antibiotic and observed to see if they react. If the patient does not have an immediate reaction they will complete a 5 days course of the antibiotic at home to assess for a delayed reactions. Patients are provided with documentation clearly stating their allergy status and which antibiotics can be safely taken. Parents and GPs are asked to update the My Health Record with their confirmed allergy status. Patients are followed-up for 12 months post intervention with a phone call at 4, 8 and 12 months.
Trial website
leadingsteps.com.au/penicillin-allergy-study
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112526 0
Dr Amy Whittaker
Address 112526 0
Leading Steps Paediatric Clinic
Pindara Specialists Suites (Benowa)
Suite 4.05, Pindara Specialist Suites,
29 Carrara Street, Benowa QLD 4217
Country 112526 0
Australia
Phone 112526 0
+61 07 55649668
Fax 112526 0
+61 07 55 395539
Email 112526 0
amy.whittaker@leadingsteps.com.au
Contact person for public queries
Name 112527 0
Ms Carmen Zentveld
Address 112527 0
Pindara Private Hospital
Allchurch Avenue
BENOWA QLD 4217
Country 112527 0
Australia
Phone 112527 0
+61 075588 9093
Fax 112527 0
Email 112527 0
ZentveldC@ramsayhealth.com.au
Contact person for scientific queries
Name 112528 0
Dr Amy Whittaker
Address 112528 0
Leading Steps Paediatric Clinic
Pindara Specialists Suites (Benowa)
Suite 4.05, Pindara Specialist Suites,
29 Carrara Street, Benowa QLD 4217
Country 112528 0
Australia
Phone 112528 0
+61 07 55649668
Fax 112528 0
+61 07 55 395539
Email 112528 0
amy.whittaker@leadingsteps.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data collected during the trial, after de-identification
When will data be available (start and end dates)?
15/04/23-30/08/28
Available to whom?
Researchers who provide a methodologically sound proposal
Available for what types of analyses?
Only to achieve the aims in the approved proposal
How or where can data be obtained?
Access subject to approval by Dr Amy Whittaker, Principal Investigator. Contact via the Clinical Trials Unit at Pindara Private Hospital (+61 075588 9093) or Leading Steps Paediatric Clinic (+61 07 55649668)


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.