Risk-stratified Testing for Safe Removal of Penicillin Allergy Labels

Deniz Göcebe

Status: Enrolling

Conditions: Hypersensitivity, Delayed; Penicillin Allergy; Hypersensitivity, Immediate; Hypersensitivity Response

Treatments: Other: standard of care; Other: Direct Oral challenge

Study type: Interventional

Funder types: Other

Identifiers

NCT06755281

S-656/2024

Details and patient eligibility

About

The aim of this clinical trial is to analyze the negative predictive capacity and safety of risk-stratified direct drug provocation tests for patients with self-reported penicillin allergies. Patients reporting immediate or delayed penicillin allergies and defined as low-risk by the PEN-FAST score will receive drug provocation tests without prior skin testing.

Full description

The PEN-FAST clinical decision rule is an internationally validated scoring system (0-5 points) that identifies low-risk patients (= a score of 0-2 points) with self-reported penicillin allergies with a negative predictive value (NPV) of over 95%. Performing direct drug provocation tests without prior skin testing on these low-risk patients was shown to be non-inferior in terms of safety and prediction of immediate allergic reactions. However, several studies have questioned the negative predictive capacity of the PEN-FAST score. In these studies, misclassifications of the PEN-FAST score were mainly based on positive skin test findings that can show false-positive results.

This study aims to validate the NPV and safety of direct drug provocation tests using the PEN-FAST score.

Participants with a PEN-FAST score of 0-2 points will directly receive a two-dose challenge (50%-50%) or single challenge (100%) with the culprit penicillin and will be monitored for at least 4 hours. No skin tests will be performed prior to the drug provocation test. Patients will be instructed to contact the hospital after the drug provocation test to monitor any delayed allergic reactions.

The outcomes will be compared to those of patients with a PEN-FAST score of 0-2 points who do not wish to skip the skin tests and who will, in parallel, receive the standard-of-care testing.

Currently, this study is approved as a single-site study.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Adult outpatients or inpatients with a penicillin allergy label
2. Willing and able to give consent.
3. PEN-FAST score of 0-2 points

Exclusion criteria

1. Age <18 years
2. Concurrent immunosuppressive therapy with 20 mg of prednisolone per day or steroid equivalent
3. Concurrent antihistamine therapy
4. Pregnancy
5. Significantly impaired general condition
6. Unstable or therapeutically inadequately controlled bronchial asthma
7. History of stem cell transplantation
8. History of acute interstitial nephritis
9. Chronic urticaria
10. Mastocytosis

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Direct drug provocation test

Experimental group

Treatment:

Other: Direct Oral challenge

Standard of care

Active Comparator group

Description:

Standard of care Skin testing and measurement of allergen-specific IgE, if negative, drug provocation test.

Treatment:

Other: standard of care