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

Primary Purpose

Hypersensitivity, Immediate, Hypersensitivity, Delayed, Hypersensitivity Response

Status

Completed

Phase

Not Applicable

Locations

International

Study Type

Interventional

Intervention

Direct oral penicillin challenge

Standard of care

About this trial

This is an interventional diagnostic trial for Hypersensitivity, Immediate focused on measuring penicillin, Low Risk allergy, direct oral challenge, standard of care, outpatient clinic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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]).

Sites / Locations

Duke University Medical Center
Vanderbilt University Medical Center
Austin Health
Peter MacCallum Cancer Center
Royal Melbourne Hospital
McGill University Health Centre (MUHC)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Direct oral antibiotic challenge

Standard of care

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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].

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]

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.

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

The proportion of patients that will respect the protocol (protocol compliance)

Proportion of patient with positive Penicillin Skin Testing

Proportion of patients with non-immune mediated positive oral provocation

Proportion of patients with severe adverse reaction - anaphylaxis/death

Time from randomization to delabelling

Number of appointments required for Penicillin delabelling

Assessment with the Pre-Questionnaire and the 6 months follow-up Questionnaire

Full Information

NCT ID

NCT04454229

First Posted

June 25, 2020

Last Updated

March 2, 2023

Sponsor

Austin Health

1. Study Identification

Unique Protocol Identification Number

NCT04454229

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

July 1, 2021 (Actual)

Primary Completion Date

December 2, 2022 (Actual)

Study Completion Date

December 2, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Austin Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypersensitivity, Immediate, Hypersensitivity, Delayed, Hypersensitivity Response

Keywords

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

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

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).

Masking

None (Open Label)

Allocation

Randomized

Enrollment

382 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Direct oral antibiotic challenge

Arm Type

Experimental

Arm Description

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

Arm Title

Standard of care

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Other

Intervention Name(s)

Direct oral penicillin challenge

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Standard of care

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Time Frame

up to 48H after oral challenge

Secondary Outcome Measure Information:

Title

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

Time Frame

Before randomization

Title

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].

Time Frame

Before randomization

Title

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]

Time Frame

Before randomization

Title

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.

Time Frame