Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000359437
Ethics application status
Approved
Date submitted
1/04/2025
Date registered
24/04/2025
Date last updated
24/04/2025
Date data sharing statement initially provided
24/04/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Single step oral provocation challenge in children with a low risk reported penicillin allergy (Safe-Step): a prospective study.
Scientific title
The safety and efficacy of a single step oral provocation challenge in children with a low risk reported penicillin allergy (Safe-Step): a prospective study.
Secondary ID [1] 313997 0
None
Universal Trial Number (UTN)
Trial acronym
One-Step
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Reported Penicillin Allergy 336727 0
Condition category
Condition code
Inflammatory and Immune System 333226 333226 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This prospective study will evaluate the outcomes of a single-dose oral provocation challenge in paediatric participants with a reported low-risk penicillin allergy. The one stage oral challenge will be undertaken as follows; the dose will be calculated in mg/kg according to the patient's weight and in accordance with the Australian Medicines Handbook paediatric dosage guidelines for the relevant penicillin. The dose will then be administered as either an oral tablet or an oral liquid, dependent on patient preference or dose dependent. In order to ensure adherence, these doses will be administered under direct supervision to ensure adherence. For the five-day extended course, the dose will be calculated as above and administered twice daily as observed by parents. and will be administered as either an oral tablet or an oral liquid, dependent of patient preference or dose dependent. There will be follow up via telephone on day 2 and say 7 of the five-day courses, to monitor adherence.

As part of routine care, the study team will review patients at the Drug Allergy Clinic, gathering relevant data from their history, medical notes, and antibiotic allergy details. This includes the type and severity of the reaction, timing of the reaction, the interval between the dose administered and the reaction, any underlying illnesses or medications at the time of the reaction, route of administration, past and current medical history, family history of allergies or co-morbidities, and the management of both acute and post-reaction phases. This information will be included in the analysis. Eligible participants will be contacted by the study team—either during their initial consultation or via telephone call following the consultation—to invite them to participate in the study.

Consented participants will then undergo a one-stage oral provocation challenge, where they will receive 100% of the calculated daily dose of penicillin based on their weight and age. Following the challenge, they will be observed for one hour in the hospital according to the Australian Society of Clinical Immunology and Allergy consensus guidelines. If no immediate reaction is observed, participants will then receive a five-day extended course of penicillin, which is the current standard clinical care.

Upon discharge, parents will be provided with an updated, approved health information sheet, which includes detailed information on potential types of reactions, their management, and the proper steps to take if a reaction occurs. The sheet also contains contact information for families to reach out if they have concerns or notice any signs of a reaction. Additionally, an email address will be provided for families to share any relevant details or photos related to a reaction.

Follow-up will take place on Day 2 and Day 7 after the initial challenge. The Day 2 phone call aims to establish contact with the family and ensure that the child is tolerating the extended treatment course without any issues. The Day 7 call is to confirm that the child has completed the course successfully and has not experienced any delayed reactions within the 48-hour post-treatment window. This allows us to update the Drug Allergy Notification, either removing the allergy label or confirming the allergy if a reaction has occurred.
Intervention code [1] 330580 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 340789 0
To assess the prevalence of reactions of one step penicillin challenge for 500 children with a reported low risk penicillin allergy, who have been referred to PCH Drug Allergy Service,
Timepoint [1] 340789 0
The children will be observed for one hour post the dose, at time of challenge.
Primary outcome [2] 341191 0
To assess safety of one step challenge, by observing and grading the severity of reactions for those children who had an immediate reaction to the one step challenge.
Timepoint [2] 341191 0
The children will be observed for one hour post the dose, at time of challenge.
Secondary outcome [1] 445074 0
To assess safety by observing and grading the severity of reactions for those children who had a delayed reaction during the five-day extended course.
Timepoint [1] 445074 0
Day 2 and Day 7 post one step challenge by telephone follow up
Secondary outcome [2] 445936 0
Assess the prevalence of a reaction to the one-step challenge during the five-day extended course.
Timepoint [2] 445936 0
Day 2 and Day 7 post one step challenge by telephone follow up

Eligibility
Key inclusion criteria
Children and young adults, male or female, aged 6 months to 18 years of age (inclusive) who have been assessed through the Drug Allergy Service with a self-reported beta-lactam penicillin allergy, with a low-risk history of a delayed non-urticarial rash who are willing to take part in this study. Low risk reported allergy is defined by mild, delayed, non-urticarial, macula/popular, or erythemous rash, mild gastro-intestinal symptoms or family history only
Minimum age
6 Months
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Females who are pregnant (Pregnancy tests will be offered to sexually active females and can be performed on the day of challenge)
• Families with the inability to give informed consent based on language barriers requiring an interpreter. (These patients will be challenged through the normal challenge clinics as per standard clinical care and therefore not disadvantaged)
• Non-beta-lactam antibiotic allergies
• Patients with a reported immediate IgE mediated reaction to a penicillin
• Patients with a reported history of a reaction to a beta-lactam cephalosporin.
• Severe cutaneous adverse reactions
• Type II-IV allergies (Serum sickness, Stevens-Johnson Syndrome (SJS), Toxic epidermal necrolysis (TEN), Acute interstitial nephritis (AIN), Drug rash eosinophilia syndrome (DRESS), Acute generalised Exanthematous Pustulosis (AGEP), Haemolytic anaemia)

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
5/05/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
500
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 27655 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 43829 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 318502 0
Hospital
Name [1] 318502 0
Perth Children's Hospital
Country [1] 318502 0
Australia
Primary sponsor type
Hospital
Name
WA Health
Address
Country
Australia
Secondary sponsor category [1] 320891 0
None
Name [1] 320891 0
N/A
Address [1] 320891 0
Country [1] 320891 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317107 0
Child and Adolescent Health Service Human Research Ethics Committee
Ethics committee address [1] 317107 0
Ethics committee country [1] 317107 0
Australia
Date submitted for ethics approval [1] 317107 0
30/06/2023
Approval date [1] 317107 0
27/09/2024
Ethics approval number [1] 317107 0

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

Contacts
Principal investigator
Name 140018 0
Prof Michaela Lucas
Address 140018 0
PCH, Dept of Immunology, Hospital Avenue, Nedlands 6009, WA
Country 140018 0
Australia
Phone 140018 0
+61864564359
Fax 140018 0
Email 140018 0
[email protected]
Contact person for public queries
Name 140019 0
Annabelle Arnold
Address 140019 0
PCH, Dept of Immunology, Hospital Avenue, Nedlands 6009, WA
Country 140019 0
Australia
Phone 140019 0
+61 8 64564359
Fax 140019 0
Email 140019 0
[email protected]
Contact person for scientific queries
Name 140020 0
Annabelle Arnold
Address 140020 0
PCH, Dept of Immunology, Hospital Avenue, Nedlands 6009, WA
Country 140020 0
Australia
Phone 140020 0
+61 8 64564359
Fax 140020 0
Email 140020 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
• Requires a scientifically sound proposal or protocol
• Requires approval by an ethics committee
• Requires a data sharing agreement between data requester and trial custodian or sponsor
What individual participant data might be shared?
• All de-identified individual participant data
What types of analyses could be done with individual participant data?
• Systematic reviews and meta-analyses
• Studies exploring new research questions
• Health economic analyses
• Studies testing whether findings can be repeated or confirmed
When can requests for individual participant data be made (start and end dates)?
From:
After publication of main results
To:
Not yet decided
Where can requests to access individual participant data be made, or data be obtained directly?
• Email of trial custodian, sponsor or committee: Email to corresponding author after publication; [email protected]

Are there extra considerations when requesting access to individual participant data?
No


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.