Hypersensitivity, Delayed, Hypersensitivity, Immediate, Hypersensitivity Response, Penicillin Allergy
Conditions
Keywords
PEN-FAST, penicillin allergy, allergy delabeling
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.
Interventions
Patients will receive a 1-step or 2-step challenge with the suspected penicillin and will be monitored for any allergic reaction within the first four hours. Patients will be instructed to contact the hospital after the drug provocation test to inquire delayed allergic reactions.
OTHERstandard of care
The patient will receive skin prick test and patch test (if a delayed allergy is suspected). Allergen-specific IgE will be measured. If all negative, drug provocation tets will be performed identical to the experimental group.
Sponsors
Deniz Göcebe
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Analysis of medical and allergic history | 1 day | (supposed) allergic symptoms |
| Penicillin allergy label | 1 day | Identification of culprit penicillin |
| Negative predictive capacity of skin tests and allergen-specific IgE | 7 days | Negative predictive values of each test alone and combined |
| 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 |
| Analysis of demographic data | 1 day | Age, sex |
Countries
Germany
Contacts
Primary ContactDeniz Göcebe, MD
Backup ContactKnut Schäkel, MD
Outcome results
None listed