The Use of Penicillin Allergy Clinical Decision Rule to Enable Direct Oral Penicillin Challenge

Not Applicable

Completed

• Conditions: Hypersensitivity, Immediate; Hypersensitivity, Delayed; Hypersensitivity Response
• Interventions: Other: Standard of care; Other: Direct oral penicillin challenge

• Registration Number: NCT04454229
• Lead Sponsor: Austin Health

Brief Summary

Whilst validated tools exist to enable inpatient penicillin assessment and de-labelling, limited evidence is available regarding the safety and efficacy in the outpatient clinic. The ability to deliver point-of-care penicillin allergy testing for a large cohort of patients, without skin testing, will improve patient access to testing and utilization of preferred penicillin antibiotics.

Detailed Description

Patient-reported penicillin allergies result in poor health outcomes for patients and drive inappropriate antibiotic prescribing, antimicrobial resistance and healthcare costs. Our group has internally and externally validated a novel penicillin allergy clinician decision rule (PEN-FAST) that is able to identify low risk penicillin allergies with a negative predictive value of 96% (95%; 94-98%). Therefore, whilst validated tools exist to enable inpatient penicillin assessment and de-labelling, limited evidence is available regarding the safety and efficacy in the outpatient clinic. The ability to deliver point-of-care penicillin allergy testing for a large cohort of patients, without skin testing, will improve patient access to testing and utilization of preferred penicillin antibiotics.

Study Timeline

• Study First Submitted: 2020-06-25
• Study First Submitted QC: 2020-06-29
• Study First Posted: 2020-07-01
• Study Start: 2021-07-01
• Primary Completion: 2022-12-02
• Study Completion: 2022-12-02
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-02
• Last Update Posted: 2023-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 382

Inclusion Criteria

1. Adult patients referred to the outpatient allergy clinic for a penicillin allergy history;
2. Willing and able to give consent.

Exclusion Criteria

1. Patient age is < 18 years;
2. Patients with a PEN-FAST score less than 3
3. Pregnancy;
4. Any other illness that, in the investigator's judgement, will substantially increase the risk associated with subject's participation in this study;
5. Patients with history of type A adverse drug reaction, drug-associated anaphylaxis, idiopathic urticaria/anaphylaxis, mastocytosis, serum sickness, blistering skin eruption or acute interstitial nephritis;
6. Patients where the allergy history was not able to be confirmed with patient;
7. Patients on concurrent antihistamine therapy;
8. Patients receiving more than stress dose steroids (i.e. > 50mg QID hydrocortisone [or steroid equivalent]).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of care	Standard of care	Standard of care: skin testing and, if negative, oral challenge.
Direct oral antibiotic challenge	Direct oral penicillin challenge	Direct oral antibiotic (penicillin) challenge in patients with PEN-Fast less than 3.

Primary Outcome Measures

Name	Time	Method
The difference in the proportion of positive oral challenges (i.e. immune-mediated reaction)	up to 48H after oral challenge

Secondary Outcome Measures

Name	Time	Method
The proportion of patients that will respect the protocol (protocol compliance)	Up to 48h after the drug challenge
Proportion of patients with severe adverse reaction - anaphylaxis/death	Up to 48h after the drug challenge
Time from randomization to delabelling	Up to 48h after the drug challenge
The proportion of patients with a penicillin allergy who experience an antibiotic associated immune mediated adverse event OR severe adverse drug reaction as per protocol definitions.	Up to 48h after the drug challenge
The proportion of patients with a penicillin allergy who experience an antibiotic associated non-immune mediated adverse event.	Up to 48h after the drug challenge
Proportion of patient with positive Penicillin Skin Testing	Up to 48h after the drug challenge
Feasibility of intervention delivery defined as the proportion of patients randomized to the intervention arm who had the intervention delivered as per protocol. [Intervention to recruitment ratio]	Before randomization
Proportion of patients referred to the outpatient allergy clinic that are eligible for intervention (i.e randomization) as per protocol [Eligibility to screened ratio]	Before randomization
Feasibility of recruitment defined as the proportion of patients consenting to participate in the study as per protocol from eligible patients. [Recruitment to eligibility ratio].	Before randomization
Proportion of patients with non-immune mediated positive oral provocation	Up to 48h after the drug challenge
Number of appointments required for Penicillin delabelling	Up to 48h after the drug challenge
Assessment with the Pre-Questionnaire and the 6 months follow-up Questionnaire	Up to 6 months after the drug challenge

Trial Locations

Locations (6)

Austin Health; 🇦🇺 Heidelberg, Victoria, Australia

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Peter MacCallum Cancer Center; 🇦🇺 Melbourne, Victoria, Australia

McGill University Health Centre (MUHC); 🇨🇦 Montreal, Quebec, Canada

Royal Melbourne Hospital; 🇦🇺 Melbourne, Victoria, Australia