Clinical trial NCT06755281: Risk-stratified Testing for Safe Removal of Penicillin Allergy Labels
Official title: Risk-stratified Testing for Safe Removal of Penicillin Allergy Labels
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Penicillin Allergy
Hypersensitivity, Immediate
Hypersensitivity, Delayed
Hypersensitivity Response
Keywords: PEN-FAST
penicillin allergy
allergy delabeling
Lead sponsor: University Hospital Heidelberg
Sponsor class: OTHER
First posted: 2025-01-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 7 days
Secondary outcomes:
measure: Negative predictive capacity of skin tests and allergen-specific IgE
timeFrame: 7 days
measure: Analysis of medical and allergic history
timeFrame: 1 day
measure: Penicillin allergy label
timeFrame: 1 day
measure: Analysis of demographic data
timeFrame: 1 day
measure: Analysis of adverse reactions
timeFrame: 7 days
measure: Analysis of medical and allergic history
timeFrame: One day
measure: Analysis of medical and allergic history
timeFrame: One day
measure: Analysis of medical and allergic history
timeFrame: One day
measure: Analysis of medical and allergic history
timeFrame: One day
measure: Analysis of internal hospital risk stratification system
timeFrame: One day
measure: Analysis of medical and allergic history
timeFrame: One day
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg, Dermatology
state: Baden-Württemberg
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg, Division of Infectious Diseases and Tropical Medicine
state: Baden-Württemberg
Study officials:
References:
citation: Copaescu AM, Vogrin S, James F, Chua KYL, Rose MT, De Luca J, Waldron J, Awad A, Godsell J, Mitri E, Lambros B, Douglas A, Youcef Khoudja R, Isabwe GAC, Genest G, Fein M, Radojicic C, Collier A, Lugar P, Stone C, Ben-Shoshan M, Turner NA, Holmes NE, Phillips EJ, Trubiano JA. Efficacy of a Clinical Decision Rule to Enable Direct Oral Challenge in Patients With Low-Risk Penicillin Allergy: The PALACE Randomized Clinical Trial. JAMA Intern Med. 2023 Sep 1;183(9):944-952. doi: 10.1001/jamainternmed.2023.2986.
citation: Trubiano JA, Vogrin S, Chua KYL, Bourke J, Yun J, Douglas A, Stone CA, Yu R, Groenendijk L, Holmes NE, Phillips EJ. Development and Validation of a Penicillin Allergy Clinical Decision Rule. JAMA Intern Med. 2020 May 1;180(5):745-752. doi: 10.1001/jamainternmed.2020.0403.