Prolonged versus single dose in penicillin oral challenge testing: protocols for a pilot and definitive randomised controlled trial (PROSPECTOR studies)
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...
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BMJ Publishing Group
2025-02-01
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| author | Vito Sabato Jason Trubiano Sara Vogrin Richard Sullivan Michael Lane Suran Fernando Fiona James Jonathan Grant Peter Morgan Rose Amy Legg Irvin Ng Ana Copaescu Elise Mitri Jack Godsell Lene Heise Garvey Philip Li |
| author_facet | Vito Sabato Jason Trubiano Sara Vogrin Richard Sullivan Michael Lane Suran Fernando Fiona James Jonathan Grant Peter Morgan Rose Amy Legg Irvin Ng Ana Copaescu Elise Mitri Jack Godsell Lene Heise Garvey Philip Li |
| author_sort | Vito Sabato |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-fe306a6ea97b4d6285e4132f07cdab31 |
| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-fe306a6ea97b4d6285e4132f07cdab312025-08-20T02:15:47ZengBMJ Publishing GroupBMJ Open2044-60552025-02-0115210.1136/bmjopen-2024-094712Prolonged versus single dose in penicillin oral challenge testing: protocols for a pilot and definitive randomised controlled trial (PROSPECTOR studies)Vito Sabato0Jason Trubiano1Sara Vogrin2Richard Sullivan3Michael Lane4Suran Fernando5Fiona James6Jonathan Grant Peter7Morgan Rose8Amy Legg9Irvin Ng10Ana Copaescu11Elise Mitri12Jack Godsell13Lene Heise Garvey14Philip Li1518 Immunology-Allergology-Rheumatology, University of Antwerp and Antwerp University Hospital, Edegem, Belgium3 National Allergy Centre of Excellence, Parkville, Victoria, Australia1 Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia5 Department of Cancer and Global Health, King`s College London, London, UK3Department of Immunology, Princess Alexandra Hospital, Brisbane, QLD, Australia9 Clinical Immunology and Allergy, Royal North Shore Hospital, St Leonards, New South Wales, AustraliaLeeds Institute of Medical Research at St James`s, University of Leeds, Leeds, UKDivision of Allergy and Clinical Immunology, Department of Medicine, Groote Schuur Hospital, University of Cape Town, Rondebosch, South Africa4 Peter MacCallum Cancer Centre, Melbourne, Victoria, AustraliaPharmacy Department, Royal Darwin Hospital, Casuarina, Northern Territory, Australia1 Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia2 Infectious Diseases and Immunology, Austin Health, Heidelberg, Victoria, Australia1 Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia2 Infectious Diseases and Immunology, Austin Health, Heidelberg, Victoria, Australia10 University of Copenhagen, Kobenhavn, Region Hovedstaden, Denmark14 Division of Rheumatology and Clinical Immunology, Department of Medicine, Hong Kong University, Hong Kong, Hong KongIntroduction 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.https://bmjopen.bmj.com/content/15/2/e094712.full |
| spellingShingle | Vito Sabato Jason Trubiano Sara Vogrin Richard Sullivan Michael Lane Suran Fernando Fiona James Jonathan Grant Peter Morgan Rose Amy Legg Irvin Ng Ana Copaescu Elise Mitri Jack Godsell Lene Heise Garvey Philip Li Prolonged versus single dose in penicillin oral challenge testing: protocols for a pilot and definitive randomised controlled trial (PROSPECTOR studies) BMJ Open |
| title | Prolonged versus single dose in penicillin oral challenge testing: protocols for a pilot and definitive randomised controlled trial (PROSPECTOR studies) |
| title_full | Prolonged versus single dose in penicillin oral challenge testing: protocols for a pilot and definitive randomised controlled trial (PROSPECTOR studies) |
| title_fullStr | Prolonged versus single dose in penicillin oral challenge testing: protocols for a pilot and definitive randomised controlled trial (PROSPECTOR studies) |
| title_full_unstemmed | Prolonged versus single dose in penicillin oral challenge testing: protocols for a pilot and definitive randomised controlled trial (PROSPECTOR studies) |
| title_short | Prolonged versus single dose in penicillin oral challenge testing: protocols for a pilot and definitive randomised controlled trial (PROSPECTOR studies) |
| title_sort | prolonged versus single dose in penicillin oral challenge testing protocols for a pilot and definitive randomised controlled trial prospector studies |
| url | https://bmjopen.bmj.com/content/15/2/e094712.full |
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