Prolonged versus single dose in penicillin oral challenge testing: protocols for a pilot and definitive randomised controlled trial (PROSPECTOR studies)

Ng, I; James, F; Copaescu, A; Vogrin, S; Mitri, E; Rose, M; Sullivan, R; Lane, M; Legg, A; Godsell, J; Fernando, S; Garvey, LH; Sabato, V; Li, P; Peter, JG; Trubiano, J

Author(s): Ng, I; James, F; Copaescu, A; Vogrin, S; Mitri, E; Rose, M; Sullivan, R; Lane, M; Legg, A; Godsell, J; Fernando, S; Garvey, LH; Sabato, V; Li, P; Peter, JG; Trubiano, J;
Details: Publication Year 2025-02-22,Volume 15,Issue #2,Page e094712
Journal Title: BMJ Open
Publication Type: Protocol
Abstract: INTRODUCTION: Penicillin allergy labels (PALs) are reported in 1 in 10 hospitalised patients globally and associated with inferior patient, hospital and microbiological outcomes; however, the majority are incorrect and should be removed. Direct oral penicillin challenge has been demonstrated to be a safe and effective method for the removal of PALs. However, the question of whether a single dose is sufficient to ascertain true allergy status remains unanswered, with some studies suggesting that extended challenges of 3 or more days are superior for the exclusion of delayed immune reactions. The aim of the PROSPECTOR studies was to determine the feasibility (PROSPECTOR-1) of a definitive trial (PROSPECTOR-2) to evaluate the safety and effectiveness of prolonged oral challenge (ie, 5 days) versus single-dose oral challenge in patients with a delayed or unknown penicillin allergy phenotype (PROSPECTOR-2). METHODS AND ANALYSIS: A pair of double-blind two-arm parallel placebo-controlled trials will be undertaken-PROlonged versus Single dose in PEnicillin oral Challenge Testing double-blind parallel group randomised placebo-cOntrolled tRial (PROSPECTOR Studies). Patients with a reported delayed or unknown timing penicillin allergy who have passed a supervised single-dose oral amoxicillin challenge (with or without prior skin testing/single or split dose) will be recruited. Informed patient consent will be granted for sites to recruit patients and collect routine clinical data. PROSPECTOR-1 will assess the safety and feasibility of a placebo-controlled trial for single-dose amoxicillin challenge versus 5-day prolonged oral challenge. PROSPECTOR-2 will assess the superiority of the 5-day prolonged oral challenge compared with single-dose amoxicillin challenge in excluding a delayed immune reaction. PROSPECTOR-2 will commence immediately post completion of PROSPECTOR-1 in a vanguard design, with adjustments to the projected sample size for superiority made following completion of PROSPECTOR-1. PROSPECTOR-2 will commence recruitment immediately following closure of PROSPECTOR-1; however, data from each trial will be analysed separately. ETHICS AND DISSEMINATION: These studies were reviewed and approved by the Austin Health Human Research Ethics Committee (PROSPECTOR-1: HREC/99740/Austin-2023 and PROSPECTOR-2: HREC/109785/Austin-2024). The results will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: PROSPECTOR-1: ACTRN12623001242617 and PROSPECTOR-2: ACTRN12624001107516.
Keywords: Humans; *Penicillins/administration & dosage/adverse effects; Administration, Oral; *Drug Hypersensitivity; Pilot Projects; Double-Blind Method; *Anti-Bacterial Agents/administration & dosage/adverse effects; Randomized Controlled Trials as Topic; Amoxicillin/administration & dosage; Skin Tests; Feasibility Studies; Antibiotics; Clinical Trial; Immunology; Public health; Protocols & guidelines
Department(s): Infectious Diseases
Publisher's Version: https://doi.org/10.1136/bmjopen-2024-094712
Open Access at Publisher's Site: https://doi.org/10.1136/bmjopen-2024-094712
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-03-21 04:37:01

Last Modified: 2025-03-21 04:37:45