Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/33326
Title: Efficacy of a Clinical Decision Rule to Enable Direct Oral Challenge in Patients With Low-Risk Penicillin Allergy: The PALACE Randomized Clinical Trial.
Austin Authors: Copaescu, Ana Maria;Vogrin, Sara;James, Fiona L ;Chua, Kyra Y L ;Rose, Morgan T ;De Luca, Joseph;Waldron, Jamie;Awad, Andrew;Godsell, Jack;Mitri, Elise A ;Lambros, Belinda;Douglas, Abby ;Youcef Khoudja, Rabea;Isabwe, Ghislaine A C;Genest, Genevieve;Fein, Michael;Radojicic, Cristine;Collier, Ann;Lugar, Patricia;Stone, Cosby;Ben-Shoshan, Moshe;Turner, Nicholas A;Holmes, Natasha E ;Phillips, Elizabeth J;Trubiano, Jason A
Affiliation: Infectious Diseases
Department of Medicine, St Vincent's Hospital, The University of Melbourne, Melbourne, Victoria, Australia.
Centre for Antibiotic Allergy and Research
The National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.;Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
The Research Institute of the McGill University Health Centre, McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
Division of Allergy and Clinical Immunology, Department of Medicine, McGill University Health Centre, McGill University, Montreal, Quebec, Canada.;The Research Institute of the McGill University Health Centre, McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
Center for Drug Safety and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.
The Research Institute of the McGill University Health Centre, McGill University Health Centre, McGill University, Montreal, Quebec, Canada.;Division of Allergy, Immunology and Dermatology, Montreal Children's Hospital, McGill University Health Centre McGill University, Montreal, Quebec, Canada.
Department of Infectious Diseases, Duke University Medical Center, Durham, North Carolina.
Center for Drug Safety and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.;Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
Issue Date: 1-Sep-2023
Date: 2023
Publication information: JAMA Internal Medicine 2023-09-01; 183(9)
Abstract: Fewer than 5% of patients labeled with a penicillin allergy are truly allergic. The standard of care to remove the penicillin allergy label in adults is specialized testing involving prick and intradermal skin testing followed by an oral challenge with penicillin. Skin testing is resource intensive, limits practice to specialist-trained physicians, and restricts the global population who could undergo penicillin allergy delabeling. To determine whether a direct oral penicillin challenge is noninferior to the standard of care of penicillin skin testing followed by an oral challenge in patients with a low-risk penicillin allergy. This parallel, 2-arm, noninferiority, open-label, multicenter, international randomized clinical trial occurred in 6 specialized centers, 3 in North America (US and Canada) and 3 in Australia, from June 18, 2021, to December 2, 2022. Eligible adults had a PEN-FAST score lower than 3. PEN-FAST is a prospectively derived and internationally validated clinical decision rule that enables point-of-care risk assessment for adults reporting penicillin allergies. Patients were randomly assigned to either direct oral challenge with penicillin (intervention arm) or a standard-of-care arm of penicillin skin testing followed by oral challenge with penicillin (control arm). The primary outcome was a physician-verified positive immune-mediated oral penicillin challenge within 1 hour postintervention in the intention-to-treat population. Noninferiority was achieved if a 1-sided 95% CI of the risk difference (RD) did not exceed 5 percentage points (pp). A total of 382 adults were randomized, with 377 patients (median [IQR] age, 51 [35-65] years; 247 [65.5%] female) included in the analysis: 187 in the intervention group and 190 in the control group. Most patients had a PEN-FAST score of 0 or 1. The primary outcome occurred in 1 patient (0.5%) in the intervention group and 1 patient (0.5%) in the control group, with an RD of 0.0084 pp (90% CI, -1.22 to 1.24 pp). The 1-sided 95% CI was below the noninferiority margin of 5 pp. In the 5 days following the oral penicillin challenge, 9 immune-mediated adverse events were recorded in the intervention group and 10 in the control group (RD, -0.45 pp; 95% CI, -4.87 to 3.96 pp). No serious adverse events occurred. In this randomized clinical trial, direct oral penicillin challenge in patients with a low-risk penicillin allergy was noninferior compared with standard-of-care skin testing followed by oral challenge. In patients with a low-risk history, direct oral penicillin challenge is a safe procedure to facilitate the removal of a penicillin allergy label. ClinicalTrials.gov Identifier: NCT04454229.
URI: https://ahro.austin.org.au/austinjspui/handle/1/33326
DOI: 10.1001/jamainternmed.2023.2986
ORCID: 
Journal: JAMA Internal Medicine
PubMed URL: 37459086
ISSN: 2168-6114
Type: Journal Article
Appears in Collections:Journal articles

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