The Use of Penicillin Allergy Clinical Decision Rule to Enable Direct Oral Penicillin Challenge

NCT04454229 | Completed DMC

• 1 other identifier: PALACE1
• Study Type: interventional
• Target: 382
• Locations: 3 countries
• Sites: 6

Brief Summary

Whilst validated tools exist to enable inpatient penicillin assessment and de-labelling, limited evidence is available regarding the safety and efficacy in the outpatient clinic. The ability to deliver point-of-care penicillin allergy testing for a large cohort of patients, without skin testing, will improve patient access to testing and utilization of preferred penicillin antibiotics.

Conditions

Hypersensitivity, Immediate; Hypersensitivity, Delayed; Hypersensitivity Response

Keywords

penicillin; Low Risk allergy; direct oral challenge; standard of care; outpatient clinic

Outcome Measures

Primary Outcomes (1)

• The difference in the proportion of positive oral challenges (i.e. immune-mediated reaction)

  up to 48H after oral challenge

Secondary Outcomes (12)

• Proportion of patients referred to the outpatient allergy clinic that are eligible for intervention (i.e randomization) as per protocol [Eligibility to screened ratio]

  Before randomization

• Feasibility of recruitment defined as the proportion of patients consenting to participate in the study as per protocol from eligible patients. [Recruitment to eligibility ratio].

  Before randomization

• Feasibility of intervention delivery defined as the proportion of patients randomized to the intervention arm who had the intervention delivered as per protocol. [Intervention to recruitment ratio]

  Before randomization

• The proportion of patients with a penicillin allergy who experience an antibiotic associated immune mediated adverse event OR severe adverse drug reaction as per protocol definitions.

  Up to 48h after the drug challenge

• The proportion of patients with a penicillin allergy who experience an antibiotic associated non-immune mediated adverse event.

  Up to 48h after the drug challenge

Study Arms (2)

Direct oral antibiotic challenge

EXPERIMENTAL

Direct oral antibiotic (penicillin) challenge in patients with PEN-Fast less than 3.

Other: Direct oral penicillin challenge

Standard of care

ACTIVE COMPARATOR

Standard of care: skin testing and, if negative, oral challenge.

Other: Standard of care

Interventions

Direct oral penicillin challenge OTHER

The patient will receive a single dose of oral penicillin, following baseline vital signs.

Direct oral antibiotic challenge

Standard of care OTHER

Routine management as per the treating clinicians that include skin prick and intradermal beta-lactam testing, followed by oral penicillin challenge in the setting of negative skin testing.

Standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients referred to the outpatient allergy clinic for a penicillin allergy history;
• Willing and able to give consent.

You may not qualify if:

• Patient age is \< 18 years;
• Patients with a PEN-FAST score less than 3
• Pregnancy;
• Any other illness that, in the investigator's judgement, will substantially increase the risk associated with subject's participation in this study;
• Patients with history of type A adverse drug reaction, drug-associated anaphylaxis, idiopathic urticaria/anaphylaxis, mastocytosis, serum sickness, blistering skin eruption or acute interstitial nephritis;
• Patients where the allergy history was not able to be confirmed with patient;
• Patients on concurrent antihistamine therapy;
• Patients receiving more than stress dose steroids (i.e. \> 50mg QID hydrocortisone \[or steroid equivalent\]).

Sponsors & Collaborators

• Austin Health: lead

Study Sites (6)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Peter MacCallum Cancer Center

Melbourne, Victoria, 3000, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3000, Australia

Location

McGill University Health Centre (MUHC)

Montreal, Quebec, H3G 1A4, Canada

Location

Related Publications (6)

• Trubiano JA, Vogrin S, Chua KYL, Bourke J, Yun J, Douglas A, Stone CA, Yu R, Groenendijk L, Holmes NE, Phillips EJ. Development and Validation of a Penicillin Allergy Clinical Decision Rule. JAMA Intern Med. 2020 May 1;180(5):745-752. doi: 10.1001/jamainternmed.2020.0403.

  PMID: 32176248 RESULT

• Devchand M, Urbancic KF, Khumra S, Douglas AP, Smibert O, Cohen E, Sutherland M, Phillips EJ, Trubiano JA. Pathways to improved antibiotic allergy and antimicrobial stewardship practice: The validation of a beta-lactam antibiotic allergy assessment tool. J Allergy Clin Immunol Pract. 2019 Mar;7(3):1063-1065.e5. doi: 10.1016/j.jaip.2018.07.048. Epub 2018 Aug 29.

  PMID: 30172019 RESULT

• Trubiano JA, Smibert O, Douglas A, Devchand M, Lambros B, Holmes NE, Chua KY, Phillips EJ, Slavin MA. The Safety and Efficacy of an Oral Penicillin Challenge Program in Cancer Patients: A Multicenter Pilot Study. Open Forum Infect Dis. 2018 Nov 17;5(12):ofy306. doi: 10.1093/ofid/ofy306. eCollection 2018 Dec.

  PMID: 30547046 RESULT

• Copaescu AM, Vogrin S, Douglas A, Turner NA, Phillips EJ, Holmes NE, Trubiano JA. Risk of Self-Reported Penicillin Allergy Despite Removal of Penicillin Allergy Label: Secondary Analysis of the PALACE Randomized Clinical Trial. JAMA Netw Open. 2024 Aug 1;7(8):e2429621. doi: 10.1001/jamanetworkopen.2024.29621.

  PMID: 39145980 DERIVED

• Copaescu AM, Vogrin S, James F, Chua KYL, Rose MT, De Luca J, Waldron J, Awad A, Godsell J, Mitri E, Lambros B, Douglas A, Youcef Khoudja R, Isabwe GAC, Genest G, Fein M, Radojicic C, Collier A, Lugar P, Stone C, Ben-Shoshan M, Turner NA, Holmes NE, Phillips EJ, Trubiano JA. Efficacy of a Clinical Decision Rule to Enable Direct Oral Challenge in Patients With Low-Risk Penicillin Allergy: The PALACE Randomized Clinical Trial. JAMA Intern Med. 2023 Sep 1;183(9):944-952. doi: 10.1001/jamainternmed.2023.2986.

  PMID: 37459086 DERIVED

• Copaescu AM, James F, Vogrin S, Rose M, Chua K, Holmes NE, Turner NA, Stone C, Phillips E, Trubiano J. Use of a penicillin allergy clinical decision rule to enable direct oral penicillin provocation: an international multicentre randomised control trial in an adult population (PALACE): study protocol. BMJ Open. 2022 Aug 8;12(8):e063784. doi: 10.1136/bmjopen-2022-063784.

  PMID: 35940831 DERIVED

MeSH Terms

Conditions

Hypersensitivity, Immediate; Hypersensitivity, Delayed

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician-Scientist Immunology and Allergy

Model Details: Direct oral challenge in patients with PEN-Fast less than 3 Eligible patients referred to the outpatient clinic reporting a penicillin allergy will be identified and assessed with a standard clinical history and the calculation of the PEN-FAST score. PEN-FAST is a three-point clinical assessment tool recently externally validated in a multicenter study, with a PEN-FAST score of \< 3 associated with 96.7% negative predictive value. Intervention: The patient will receive a single dose of oral penicillin, following baseline vital signs (i.e. temperature, heart rate, blood pressure, respiratory rate, skin check). Nursing staff will repeat vital signs as needed and after oral challenge while observing for signs of an immune mediated adverse reaction. If at any stage an antibiotic associated adverse event is noted, standard of care treatment is offered by the attending clinicians (ex. adrenalin for immediate hypersensitivity reaction).

Study Record Dates

• First Submitted: June 25, 2020
• First Posted: July 1, 2020
• Study Start: July 1, 2021
• Primary Completion: December 2, 2022
• Study Completion: December 2, 2022
• Last Updated: March 6, 2023

Record last verified: 2023-03

Locations

AU (3); CA (1); US (2)