Oral challenge vs routine care to assess low-risk penicillin allergy in critically ill hospital patients (ORACLE): a pilot randomised controlled trial

Pilot and Feasibility Studies

Study Protocol

Fiona James¹  Grace Gibney¹  Natasha Holmes²  Morgan Rose³  Jason Trubiano⁴  Trisha Peel⁵  Glenn Eastwood⁶  Sara Vogrin⁷  Brendan Murfin⁸  Ben Rogers⁹  Sara Barnes^1,10  Belinda Lambros^1,11  Monica Slavin^1,12  Michelle Phung^1,13 

[1] Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Level 7, Harold Stokes Building, 145 Studley Road, 3084, Heidelberg, VIC, Australia;Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Level 7, Harold Stokes Building, 145 Studley Road, 3084, Heidelberg, VIC, Australia;Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia;Data Analytics Research and Evaluation Centre, Austin Health/University of Melbourne, Heidelberg, VIC, Australia;Department of Critical Care, The University of Melbourne, Parkville, VIC, Australia;Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Level 7, Harold Stokes Building, 145 Studley Road, 3084, Heidelberg, VIC, Australia;National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia;Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia;Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Level 7, Harold Stokes Building, 145 Studley Road, 3084, Heidelberg, VIC, Australia;National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia;Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia;Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia;Department of Infectious Diseases, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia;Department of Infectious Diseases, Alfred Health, Melbourne, VIC, Australia;Department of Intensive Care, Austin Hospital, Heidelberg, VIC, Australia;Department of Medicine (St Vincent’s Hospital), University of Melbourne, Melbourne, VIC, Australia;Intensive Care Unit, Monash Health, Clayton, VIC, Australia;Monash Infectious Diseases, Monash Health, Clayton, VIC, Australia;School of Clinical Sciences, Monash University, Clayton, VIC, Australia;Monash Lung Sleep Allergy and Immunology, Monash Health, Clayton, VIC, Australia;National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia;Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia;National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia;Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia;Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia;Immunocompromised Host Infection Service, Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, VIC, Australia;Pharmacy Department, Monash Health, Clayton, VIC, Australia;Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, Australia;

关键词: Allergy;    Delabelling;    Antibiotics;    Penicillin;    Intensive care;    Critical illness;   

DOI  :  10.1186/s40814-023-01337-8

 received in 2023-01-13, accepted in 2023-06-07,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundSelf-reported penicillin allergies are highly prevalent in hospitalised patients and are associated with poor health and health service outcomes. Critically ill patients have historically been underrepresented in prospective delabelling studies in part due to concerns around clinical stability and reliability of penicillin skin testing. Allergy assessment tools exist to identify low-risk penicillin allergy phenotypes and facilitate direct oral challenge delabelling. PEN-FAST is a clinical decision rule that has been validated to predict true penicillin allergy in a cohort of non-critically ill patients. There is however limited evidence regarding the feasibility, safety and efficacy of direct oral challenges and the use of delabelling clinical decisions rules in the intensive care setting.MethodsCritically ill patients in the intensive care unit (ICU) with low-risk penicillin allergy phenotypes (PEN-FAST score < 3) will be randomised 1:1 to direct oral penicillin challenge (single dose 250 mg oral amoxicillin or implicated penicillin) or routine care, followed by a 2-h observation period. Patients will receive a second oral challenge/observation prior to hospital discharge (with subsequent observation for 2 h). An assessment for antibiotic-associated adverse events will also be undertaken at 24 h and 5 days post each challenge/observation and again at 90 days post-randomisation. The primary outcome measures are feasibility (proportion of eligible patients recruited and protocol compliance) and safety (proportion of patients who experience an antibiotic-associated immune-mediated adverse event or serious adverse event).DiscussionWe will report the feasibility and safety of point-of-care penicillin direct oral challenge in this first randomised controlled trial of low-risk penicillin allergy in critically ill hospitalised patients. Upon completion of the project, important findings will inform the design of planned large prospective multi-centre clinical trials in Australian and international ICUs, further examining safety and efficacy and exploring antimicrobial prescribing-related outcomes following penicillin oral challenge.Trial registrationAustralian New Zealand Clinical Trials RegistryRegistration Number: ACTRN12621000051842Date registered: 20/01/2021https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379735&isReview=true

【 授权许可】

CC BY   
© The Author(s) 2023

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Fig. 9