Direct Oral Challenges in Private Practice Setting to Delabeling Children With Beta-lactam Allergy

Official title

Feasibility of Direct Oral Challenges in Private Practice Setting for the Evaluation of Mild Delayed Reactions to Beta-lactams in Children

Overview

The purpose of this study is to demonstrate the feasibility of direct oral challenge performed in private practice setting for children with suspected benign delayed allergy to beta-lactams. The results of this study could help establish recommendations for conducting direct oral challenge in primary care settings to delabeling children with benign delayed reactions to beta-lactams.

Detailed description

Approximately 10% of children are labeled as allergic to beta-lactams (BL). Consequently, they receive alternative antibiotics with a broader spectrum but lower efficacy, leading to increased infectious morbidity and mortality, a higher risk of colonization with antibiotic-resistant bacteria, and elevated healthcare costs. However, true BL allergy is only confirmed in 5-10% of cases. Therefore, an essential challenge is to promptly identify non-allergic children to prevent unnecessary medical restrictions.

The most common reactions are delayed and benign. Current guidelines recommend evaluating these reactions through direct oral challenge (DOC) without prior allergological assessment, as traditional diagnostic methods, particularly skin tests, have poor sensitivity in this context. However, the optimal setting for conducting these tests remains debated, particularly regarding whether they can be initiated in hospital settings or private medical practices.

To date, over 8,300 DOCs have been performed in children, predominantly in hospital-based consultations. These tests have demonstrated a favorable safety profile, with positive DOC reactions often being of the same nature and less severe than the initial reported reaction. While many physicians perform DOCs in private practice, data on their use in pediatric populations remain scarce.

The primary objective of this study is to assess the feasibility of DOCs conducted in private medical practices for children with suspected benign delayed allergy to BL

Primary outcome measures

• Feasibility of direct oral challenge (DOC) for beta-lactam allergy assessment [Time frame: Day 14]

Secondary outcome measures (7)

• Negative and positive tests reaction nature comparison [Time frame: Day 14]
• Negative and positive tests reaction chronology comparison [Time frame: Day 14]
• Negative and positive tests reaction duration comparison [Time frame: Day 14]
• Negative and positive tests reactions index comparison [Time frame: Day 14]
• Reactions nature in positive tests [Time frame: Day 14]
• Reactions extension in positive tests [Time frame: Day 14]
• Reactions duration in positive tests [Time frame: Day 14]

Eligibility criteria

Inclusion criteria

• Population: Children's age between 0 and 17 years
• Child who has undergone a direct oral challenge in a private medical practice and a follow-up consultation within 7 to 14 days for suspected delayed allergy to amoxicillin +/- clavulanate or cefpodoxime or cefixime with the following characteristics:
• delayed reaction (onset > 1 hour after treatment start),
• mild reaction (isolated urticaria or Maculopapular exanthema),
• Absence of warning signs suggestive of a severe cutaneous adverse reaction (erythroderma, presence of bullae, vesicles, pustules, target lesions, involvement of oral, genital, or ocular mucosa, facial edema, general condition impairment, organ failure, duration > 7 days).

Exclusion criteria

• Informed children or holders of parental authority objecting to the use of patient data in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

France · 1 center

• Hôpital Necker - Enfants Malades — Paris

Publications

• Castells M, Khan DA, Phillips EJ. Penicillin Allergy. N Engl J Med. 2019 Dec 12;381(24):2338-2351. doi: 10.1056/NEJMra1807761. No abstract available. PMID 31826341
• Khan DA, Banerji A, Blumenthal KG, Phillips EJ, Solensky R, White AA, Bernstein JA, Chu DK, Ellis AK, Golden DBK, Greenhawt MJ, Horner CC, Ledford D, Lieberman JA, Oppenheimer J, Rank MA, Shaker MS, Stukus DR, Wallace D, Wang J; Chief Editor(s):; Khan DA, Golden DBK, Shaker M, Stukus DR; Workgroup Contributors:; Khan DA, Banerji A, Blumenthal KG, Phillips EJ, Solensky R, White AA; Joint Task Force PMID 36122788
• Gomes ER, Brockow K, Kuyucu S, Saretta F, Mori F, Blanca-Lopez N, Ott H, Atanaskovic-Markovic M, Kidon M, Caubet JC, Terreehorst I; ENDA/EAACI Drug Allergy Interest Group. Drug hypersensitivity in children: report from the pediatric task force of the EAACI Drug Allergy Interest Group. Allergy. 2016 Feb;71(2):149-61. doi: 10.1111/all.12774. Epub 2015 Nov 17. PMID 26416157
• Sousa-Pinto B, Tarrio I, Blumenthal KG, Araujo L, Azevedo LF, Delgado L, Fonseca JA. Accuracy of penicillin allergy diagnostic tests: A systematic review and meta-analysis. J Allergy Clin Immunol. 2021 Jan;147(1):296-308. doi: 10.1016/j.jaci.2020.04.058. Epub 2020 May 21. PMID 32446963
• Srisuwatchari W, Phinyo P, Chiriac AM, Saokaew S, Kulalert P. The Safety of the Direct Drug Provocation Test in Beta-Lactam Hypersensitivity in Children: A Systematic Review and Meta-Analysis. J Allergy Clin Immunol Pract. 2023 Feb;11(2):506-518. doi: 10.1016/j.jaip.2022.11.035. Epub 2022 Dec 14. PMID 36528293
• Demoly P, Adkinson NF, Brockow K, Castells M, Chiriac AM, Greenberger PA, Khan DA, Lang DM, Park HS, Pichler W, Sanchez-Borges M, Shiohara T, Thong BY. International Consensus on drug allergy. Allergy. 2014 Apr;69(4):420-37. doi: 10.1111/all.12350. PMID 24697291
• Chow TG, Patel G, Mohammed M, Johnson D, Khan DA. Delabeling penicillin allergy in a pediatric primary care clinic. Ann Allergy Asthma Immunol. 2023 May;130(5):667-669. doi: 10.1016/j.anai.2023.01.034. Epub 2023 Feb 2. No abstract available. PMID 36738783
• Savic L, Ardern-Jones M, Avery A, Cook T, Denman S, Farooque S, Garcez T, Gold R, Jay N, Krishna MT, Leech S, McKibben S, Nasser S, Premchand N, Sandoe J, Sneddon J, Warner A. BSACI guideline for the set-up of penicillin allergy de-labelling services by non-allergists working in a hospital setting. Clin Exp Allergy. 2022 Oct;52(10):1135-1141. doi: 10.1111/cea.14217. Epub 2022 Sep 21. PMID 36128691

Identifiers

NCT: NCT07002814 · APHP250276 · ID-RBC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗