Risk-stratified Testing for Safe Removal of Penicillin Allergy Labels

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое Direct Oral challenge
  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.
• Другое standard 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.

Первичные конечные точки

• 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 [Срок оценки: 7 days]

Вторичные конечные точки (11)

• Negative predictive capacity of skin tests and allergen-specific IgE [Срок оценки: 7 days]
• Analysis of medical and allergic history [Срок оценки: 1 day]
• Penicillin allergy label [Срок оценки: 1 day]
• Analysis of demographic data [Срок оценки: 1 day]
• Analysis of adverse reactions [Срок оценки: 7 days]
• Analysis of medical and allergic history [Срок оценки: One day]
• Analysis of medical and allergic history [Срок оценки: One day]
• Analysis of medical and allergic history [Срок оценки: One day]
• Analysis of medical and allergic history [Срок оценки: One day]
• Analysis of internal hospital risk stratification system [Срок оценки: One day]
• Analysis of medical and allergic history [Срок оценки: One day]

Критерии участия

Критерии включения

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

Критерии исключения

• Age <18 years
• Concurrent immunosuppressive therapy with 20 mg of prednisolone per day or steroid equivalent
• Concurrent antihistamine therapy
• Pregnancy
• Significantly impaired general condition
• Unstable or therapeutically inadequately controlled bronchial asthma
• History of stem cell transplantation
• History of acute interstitial nephritis
• Chronic urticaria
• Mastocytosis

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Германия · 2 центра

• University Hospital Heidelberg, Dermatology — Heidelberg
• University Hospital Heidelberg, Division of Infectious Diseases and Tropical Medicine — Heidelberg

Публикации

• 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 PALAC PMID 37459086
• 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. PMID 32176248

Идентификаторы

NCT: NCT06755281 · S-656/2024

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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