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 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.