Risk-stratified Testing for Safe Removal of Penicillin Allergy Labels

Not Applicable

Recruiting

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

• Registration Number: NCT06755281
• Lead Sponsor: Deniz Göcebe

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2024-12-22
• Study First Submitted QC: 2024-12-22
• Study First Posted: 2025-01-01
• Study Start: 2025-01-08
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-09
• Last Update Posted: 2025-04-10
• Primary Completion: 2026-12
• Study Completion: 2027-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
The difference in the proportion of patients with any positive finding in skin tests, allergen-specific IgE or drug provocation test between the two groups	7 days	Percentage of subjects that retain their allergy label as they show at least one positive finding in skin tests, allergen-specific IgE or drug provocation test.

Secondary Outcome Measures

Name	Time	Method
Negative predictive capacity of skin tests and allergen-specific IgE	7 days	Negative predictive values of each test alone and combined
Analysis of medical and allergic history	One day	(supposed) allergic symptoms
Penicillin allergy label	1 day	Identification of culprit penicillin
Analysis of demographic data	1 day	Age, sex
Analysis of adverse reactions	7 days	Detailed analysis of any (supposed) allergic reactions following drug provocation test
Analysis of internal hospital risk stratification system	One day	Measurement of score of internal hospital risk stratification system

Trial Locations

Locations (2)

University Hospital Heidelberg, Division of Infectious Diseases and Tropical Medicine; 🇩🇪 Heidelberg, Baden-Württemberg, Germany

University Hospital Heidelberg, Dermatology; 🇩🇪 Heidelberg, Baden-Württemberg, Germany