Amoxicillin Challenge for Penicillin Allergy Diagnosis

Study Overview
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Brief Summary
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False diagnosis of penicillin allergy are frequently reported, and have been proven detrimental to patients. Current guidelines for the assessment of drug allergies recommend that penicillin allergy be evaluated first with prick and intradermal skin tests, and then completed with a graded oral challenge, spread over at least two doses. However, it has been shown that these skin tests, in addition to consuming resources and time, are of limited, or even doubtful validity, given the poor predictive values that have been reported in the modern penicillins era. It now seems unreasonable to continue their use without addressing other, more efficient diagnostic stategies. Several groups have now demonstrated the safety, validity, and efficiency of a direct, two-step amoxicillin oral challenge (starting with 10% of the standard therapeutic dose, followed by 90 % of the dose), without prior skin tests, first for any type of reaction in the pediatric population, then for any non-immediate reaction in the adult population. The objective of this study is to demonstrate the safety, efficiency, and validity of direct, two-step graded oral challenge with amoxicillin for the evaluation of any reported penicillin allergy in the adult population, excluding high-risk patients (documented anaphylaxis to a penicillin in the last 5 years). Skin tests will first be performed according to the protocol currently in use at the CHUL, then consented patients will proceed with the graded oral challenge still according to the protocol currently in use at the CHUL, but regardless of the skin tests results. The results of the two tests will be compared to determine the safety, efficiency and validity of proceeding directly to the graded oral challenge.

Official Title
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Safety, Validity and Efficiency of a Direct Graded Oral Challenge With Amoxicillin for the Evaluation of Penicillin Allergy in Adults

Conditions
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Penicillin Allergy

Intervention / Treatment
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* Diagnostic Test: Penicillin Skin Testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Being 18 years of age or older at the time of the test Being referred by a health professional for the evaluation of any allergic reaction to a penicillin, including natural penicillins, anti-staphylococcal penicillins, aminopenicillins, penicillins combined with a beta-lactamase inhibitor, and carboxypenicillins ; or an antibiotic of the beta-lactam family, whose assessment requires testing for penicillins, according to the treating allergist Exclusion Criteria: Pregnancy Poorly controlled asthma, chronic lung disease or heart disease Failure to stop beta-blockers prior to the test Occurrence of the reaction in the 4 weeks preceding the test (possibility of false negatives) History of severe delayed hypersensitivity reaction, reaction requiring hospitalization of more than 24 hours, or bullous, pustular, exfoliative or mucosal reaction (excluding angioedema) Recent anaphylaxis (<5 years), defined as concomitant involvement of at least two systems (respiratory, digestive, mucocutaneous or cardiovascular) within one hour of administration of the drug

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Skin testing and Graded Oral Challenge<br>Penicillin skin testing as described in the intervention section, followed by amoxicillin graded oral challenge as described in the intervention section | Diagnostic Test: Penicillin Skin Testing<br>* Skin test protocol: prick skin tests (penicilloyl-polylysine 0.000012 mol/0.05 mL, penicillin G 10,000 U/mL, penoate 10,000 U/mL, ampicillin 100 mg/mL, amoxicillin 71 mg/mL, histamine/positive control, diluent/negative control), then intradermal skin tests (penicilloyl-polylysine 0.000012 mol/0.05 mL, penicillin G 10,000 U/mL, penoate 10,000 U/mL, ampicillin 1 mg/mL, diluent/negative control), administered as an intradermal injection of a standardized volume of 0.02 mL. Graded oral challenge with amoxicillin : a first dose of 50 mg of amoxicillin; 20-minute observation period; in the absence of any objective symptom of an allergic reaction, a second dose of amoxicillin of 450 mg; final observation period of 60 minutes, under nurse and medical supervision.<br>* Other names: Amoxicillin Graded Oral Challenge;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Type 1 Hypersensitivity Reaction | The primary outcome is the occurrence of immediate hypersensitivity symptoms, occuring during the test period, which is up to 60 minutes after the last dose of amoxicillin. | 60 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skin Tests Results | Concordance of Skin Tests Results with Oral Challenge Results | 60 minutes | 
| Severity of immediate hypersensitivity symptoms | Mild, moderate and severe | 60 minutes | 
| Delayed hypersensitivity symptoms | Occurrence of delayed hypersensitivity symptoms | 14 days |