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

Hypersensitivity, Immediate Clinical Trial

— PALACE  

Official title:

The Use of Penicillin Allergy Clinical Decision Rule to Enable Direct Oral Penicillin Challenge - An International Multicenter Randomized Control Trial - The PALACE Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04454229
• Other study ID #: PALACE1
• Status: Completed
• Phase: N/A
• Start date: July 1, 2021
• Est. completion date: December 2, 2022

Study information

• Verified date: March 2023
• Source: Austin Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Patient-reported penicillin allergies result in poor health outcomes for patients and drive inappropriate antibiotic prescribing, antimicrobial resistance and healthcare costs. Our group has internally and externally validated a novel penicillin allergy clinician decision rule (PEN-FAST) that is able to identify low risk penicillin allergies with a negative predictive value of 96% (95%; 94-98%). Therefore, 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 382
• Est. completion date: December 2, 2022
• Est. primary completion date: December 2, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult patients referred to the outpatient allergy clinic for a penicillin allergy history;

2. Willing and able to give consent.

Exclusion Criteria:

1. Patient age is < 18 years;

2. Patients with a PEN-FAST score less than 3

3. Pregnancy;

4. Any other illness that, in the investigator's judgement, will substantially increase the risk associated with subject's participation in this study;

5. 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;

6. Patients where the allergy history was not able to be confirmed with patient;

7. Patients on concurrent antihistamine therapy;

8. Patients receiving more than stress dose steroids (i.e. > 50mg QID hydrocortisone [or steroid equivalent]).

Related Conditions & MeSH terms

• Hypersensitivity
• Hypersensitivity Response
• Hypersensitivity, Delayed
• Hypersensitivity, Immediate

Intervention

Other:
• Direct oral penicillin challenge
The patient will receive a single dose of oral penicillin, following baseline vital signs.
• Standard of care
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.

Locations

Country	Name	City	State
Australia	Austin Health	Heidelberg	Victoria
Australia	Peter MacCallum Cancer Center	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Canada	McGill University Health Centre (MUHC)	Montreal	Quebec
United States	Duke University Medical Center	Durham	North Carolina
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Austin Health

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

References & Publications (3)

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. — View Citation

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):o — View Citation

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/jamaint — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The difference in the proportion of positive oral challenges (i.e. immune-mediated reaction)		up to 48H after oral challenge
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	The proportion of patients that will respect the protocol (protocol compliance)		Up to 48h after the drug challenge
Secondary	Proportion of patient with positive Penicillin Skin Testing		Up to 48h after the drug challenge
Secondary	Proportion of patients with non-immune mediated positive oral provocation		Up to 48h after the drug challenge
Secondary	Proportion of patients with severe adverse reaction - anaphylaxis/death		Up to 48h after the drug challenge
Secondary	Time from randomization to delabelling		Up to 48h after the drug challenge
Secondary	Number of appointments required for Penicillin delabelling		Up to 48h after the drug challenge
Secondary	Assessment with the Pre-Questionnaire and the 6 months follow-up Questionnaire		Up to 6 months after the drug challenge