PT  - JOURNAL ARTICLE
AU  - Ng, Irvin
AU  - James, Fiona
AU  - Copaescu, Ana
AU  - Vogrin, Sara
AU  - Mitri, Elise
AU  - Rose, Morgan
AU  - Sullivan, Richard
AU  - Lane, Michael
AU  - Legg, Amy
AU  - Godsell, Jack
AU  - Fernando, Suran
AU  - Garvey, Lene Heise
AU  - Sabato, Vito
AU  - Li, Philip
AU  - Peter, Jonathan Grant
AU  - Trubiano, Jason
TI  - Prolonged versus single dose in penicillin oral challenge testing: protocols for a pilot and definitive randomised controlled trial (PROSPECTOR studies)
AID  - 10.1136/bmjopen-2024-094712
DP  - 2025 Feb 01
TA  - BMJ Open
PG  - e094712
VI  - 15
IP  - 2
4099  - http://bmjopen.bmj.com/content/15/2/e094712.short
4100  - http://bmjopen.bmj.com/content/15/2/e094712.full
SO  - BMJ Open2025 Feb 01; 15
AB  - 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.