Hypersensitivity, Delayed, Hypersensitivity, Immediate, Hypersensitivity Response
Conditions
Keywords
penicillin, Low Risk allergy, direct oral challenge, standard of care, outpatient clinic
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.
Interventions
OTHERDirect oral penicillin challenge
The patient will receive a single dose of oral penicillin, following baseline vital signs.
OTHERStandard of care
Routine management as per the treating clinicians that include skin prick and intradermal beta-lactam testing, followed by oral penicillin challenge in the setting of negative skin testing.
Sponsors
Austin Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Direct oral challenge in patients with PEN-Fast less than 3 Eligible patients referred to the outpatient clinic reporting a penicillin allergy will be identified and assessed with a standard clinical history and the calculation of the PEN-FAST score. PEN-FAST is a three-point clinical assessment tool recently externally validated in a multicenter study, with a PEN-FAST score of \< 3 associated with 96.7% negative predictive value. Intervention: The patient will receive a single dose of oral penicillin, following baseline vital signs (i.e. temperature, heart rate, blood pressure, respiratory rate, skin check). Nursing staff will repeat vital signs as needed and after oral challenge while observing for signs of an immune mediated adverse reaction. If at any stage an antibiotic associated adverse event is noted, standard of care treatment is offered by the attending clinicians (ex. adrenalin for immediate hypersensitivity reaction).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 \[or steroid equivalent\]).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The difference in the proportion of positive oral challenges (i.e. immune-mediated reaction) | up to 48H after oral challenge |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| The proportion of patients that will respect the protocol (protocol compliance) | Up to 48h after the drug challenge |
| 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 |
| Proportion of patients with non-immune mediated positive oral provocation | 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 |
| 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 |
| Proportion of patient with positive Penicillin Skin Testing | Up to 48h after the drug challenge |
Countries
Australia, Canada, United States
Outcome results
None listed