Allergy De-Labeling for Amoxicillin Allergy

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: The Hospital for Sick Children

Disqualifiers: Unable to consent or assent

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a program to determine if children labeled as allergic to amoxicillin, a common antibiotic, can safely take it without issues. Many children may have been labeled with an allergy after mild symptoms like rashes, but they might not be truly allergic. The trial aims to "delabel" these children by administering a small dose of amoxicillin under supervision to check for any reaction. Children who have reported mild allergy symptoms, such as rashes or upset stomach, and have not experienced severe reactions before might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to benefit from this new approach.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

What prior data suggests that the Allergy De-Labeling Program is safe for children?

Previous studies have shown promising safety results in removing penicillin allergy labels. Most children labeled as allergic to penicillin actually tolerate the drug well. Research indicates that many reported allergies are mistaken, often due to unrelated rashes appearing days later. Specifically, only about 1 in 205 children with mild symptoms, such as mild rashes, reacted after taking a test dose of the antibiotic. These findings suggest that the oral challenge used in the Allergy De-Labeling Program is generally safe and well-tolerated for children considered low-risk. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it offers a new approach to managing reported amoxicillin allergies. Unlike traditional methods that often rely on avoiding the drug or conducting allergist-supervised testing, this trial uses a structured risk assessment to identify patients who can safely undergo an oral provocation challenge (OPC). This process could help "de-label" patients mistakenly identified as allergic, allowing them to use amoxicillin without fear. By systematically distinguishing between low-risk and high-risk allergy symptoms, this trial aims to reduce unnecessary avoidance of a valuable antibiotic, potentially improving treatment options for patients who need it.

What evidence suggests that this Allergy De-Labeling Program is effective for amoxicillin allergy?

Research has shown that most children thought to be allergic to penicillin, such as amoxicillin, can actually take the drug without issues. Studies reveal that over 95% of people who believe they have a penicillin allergy do not react adversely when tested. This indicates they can safely use these antibiotics. In this trial, participants will undergo a systematic allergy risk assessment to determine their eligibility for an oral challenge. A review found that testing to remove the allergy label is both effective and safe. Programs reassessing penicillin allergies have successfully demonstrated that many children are not truly allergic, allowing them to use more effective antibiotics with fewer side effects. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for children who have been labeled with an allergy to antibiotics like penicillin or amoxicillin, but might not truly be allergic. They should be visiting the emergency department and willing to undergo an 'oral challenge' to potentially remove the allergy label.

Inclusion Criteria

I am between 1 month and 18 years old and have a reported bee sting allergy.

Exclusion Criteria

I or my guardian cannot give consent.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Risk Assessment

Systematic allergy risk assessment to stratify patients' reported symptoms as low or high risk

1 day

1 visit (in-person)

Oral Challenge

Eligible patients undergo an oral provocation challenge with Amoxicillin and are observed for 1 hour

1 day

1 visit (in-person)

Follow-up

Participants are monitored for any adverse reactions up to 2 weeks after the oral challenge

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Allergy De-Labeling Program

Trial Overview The study is testing a program where children in the emergency department are given a questionnaire and then take amoxicillin under supervision. The goal is to see if they can tolerate it without allergic reactions, effectively 'delabeling' their supposed allergy.

How Is the Trial Designed?

Group I: Eligible for study risk assessment questionnaire Experimental Treatment 1 Intervention

First, a systematic allergy risk assessment tool will enable stratification of patients' reported symptoms as (1) low risk (eg, isolated urticarial, maculopapular rash, gastrointestinal symptoms) or (2) high risk (eg, anaphylaxis, severe systemic reactions). Only patients classified low risk will be eligible for OPC for allergy delabeling. Patients' ineligible for OPC because of history of high-risk allergy symptoms or presence of clinical confounders for OPC (eg, uncontrolled asthma) will be referred to the SickKids allergy clinic for further evaluation.

Group II: Eligible for oral challenge in the emergency department Experimental Treatment 2 Interventions

A subset of patients screened with the risk assessment questionnaire will fulfill eligibility criteria to undergo the Oral provocation challenge. Specifically, these will be patients who (1) fulfill several procedural requirements (eg, parent able to observe child for 1 hour after OPC), (2) have a previously unevaluated allergy label without high-risk features and without any clinical confounders for the OPC, and (3) meet other clinical criteria for OPC (eg, vital signs within normal range). These participants will be given a one-time dose of Amoxicillin 17 mg/kg (maximum, 500 mg) and observed for 1 hour for a reaction.

Who Is Running the Clinical Trial?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

Published Research Related to This Trial

The PEN-FAST clinical decision rule effectively identifies low-risk penicillin allergies in a high-risk population, with a strong discrimination ability (AUC of 0.86) based on a study of 142 patients, most of whom reported anaphylaxis.

Using a cutoff of less than 3 points on the PEN-FAST score, only 6.9% of patients classified as low risk tested positive for an allergy, demonstrating a high negative predictive value (0.93) for safely delabeling amoxicillin allergy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive factors of amoxicillin immediate hypersensitivity and validation of PEN-FAST clinical decision rule. Piotin, A., Godet, J., Trubiano, JA., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6824919/

The Challenge of De-labeling Penicillin Allergy - PMC Penicillin allergy labels directly impact antimicrobial stewardship by leading to use of less effective and broader spectrum antimicrobials and are associated ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1201971222006178

The effectiveness of interventions that support penicillin ... Penicillin allergy delabeling by nonallergists is efficacious and safe. The proportion of assessed patients who can be delabeled increases with the complexity ...

3. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/2806976

Efficacy of a Clinical Decision Rule to Enable Direct Oral ... More than 95% of patients labeled as penicillin allergic will have negative penicillin allergy testing and tolerate subsequent exposure.

4. nature.com nature.com/articles/s44259-024-00035-6

Narrative review of recent developments and the future ... This article outlines recent developments in non-allergist delivered penicillin allergy de-labelling (PADL), discusses remaining controversies and uncertainties

5. all-imm.com all-imm.com/index.php/aei/article/view/1360/2056

Effectiveness of a penicillin allergy delabeling program— ... Among 121 participants who completed the protocol, penicillin allergy was confirmed in 13 (10.74%) patients, and the label was retained in an ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06823154

The Implementation and Impact of an Allergy De-Labeling ... Some children can have reactions to these antibiotics that can be mistaken as an allergy, especially rashes that develop days to weeks later. In ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0883944124004647

Antibiotic allergy de-labeling in the intensive care unit High risk allergies were confirmed in 11 patients (18 %). The study resulted in increased penicillin use and decreased broad-spectrum antibiotic use. No adverse ...

8. jacionline.org jacionline.org/article/S0091-6749(23)01688-3/fulltext

QI Project: De-labeling Low Risk Penicillin Allergies on the ... An erroneous penicillin allergy label (PAL) leads to less optimal and more expensive antibiotics while contributing to the rise of antimicrobial resistance.

9. blogs.cdc.gov blogs.cdc.gov/safehealthcare/antibiotic-stewardship-and-allergy-labels/

Antibiotic Stewardship when an Allergy Label is Present ... Results showed 60-70% of the patients reported low-risk symptoms. Over two years, 1 in 205 low-risk patients had a rash after a test dose of ...