Hypersensitivity, ImmediatePALACENCT04454229
The Use of Penicillin Allergy Clinical Decision Rule to Enable Direct Oral Penicillin Challenge
A study testing Direct oral penicillin challenge in people with Hypersensitivity, Immediate and Hypersensitivity, Delayed, run by Austin Health at 6 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypersensitivity, Immediate, Hypersensitivity, Delayed, Hypersensitivity Response
- What is being tested?
- Direct oral penicillin challenge
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 382 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 1 Jul 2021to 2 Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients referred to the outpatient allergy clinic for a penicillin allergy history;
- Willing and able to give consent.
Who cannot join
- 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]).
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
Australia3 sites
Austin Health
Heidelberg, Victoria, 3084
Peter MacCallum Cancer Center
Melbourne, Victoria, 3000
Royal Melbourne Hospital
Melbourne, Victoria, 3000
United States2 sites
Duke University Medical Center
Durham, North Carolina, 27710
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
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
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.
Read the 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.
- Being tested
- Direct oral penicillin challenge, Standard of care
- Keywords
- penicillin, Low Risk allergy, direct oral challenge, standard of care, outpatient clinic
- Medical subject headings
- Hypersensitivity, Immediate, Hypersensitivity, Delayed
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Direct oral penicillin challengeOther
The patient will receive a single dose of oral penicillin, following baseline vital signs.
Standard of careOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Direct oral antibiotic challenge | Experimental | Direct oral antibiotic (penicillin) challenge in patients with PEN-Fast less than 3. Receives: Other: Direct oral penicillin challenge |
| Standard of care | Active comparator | Standard of care: skin testing and, if negative, oral challenge. Receives: Other: Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
The difference in the proportion of positive oral challenges (i.e. immune-mediated reaction)
Measured: 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]
Measured: 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].
Measured: 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]
Measured: 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.
Measured: 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.
Measured: Up to 48h after the drug challenge
The proportion of patients that will respect the protocol (protocol compliance)
Measured: Up to 48h after the drug challenge
Proportion of patient with positive Penicillin Skin Testing
Measured: Up to 48h after the drug challenge
Proportion of patients with non-immune mediated positive oral provocation
Measured: Up to 48h after the drug challenge
Proportion of patients with severe adverse reaction - anaphylaxis/death
Measured: Up to 48h after the drug challenge
Time from randomization to delabelling
Measured: Up to 48h after the drug challenge
Number of appointments required for Penicillin delabelling
Measured: Up to 48h after the drug challenge
Assessment with the Pre-Questionnaire and the 6 months follow-up Questionnaire
Measured: Up to 6 months after the drug challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2020
- Study start1 Jul 2021
- Primary completion2 Dec 2022
- Study completion2 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Hypersensitivity, ImmediateStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 382 participants (actual)
Sponsor and investigators
- Lead sponsor
- Austin Health
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Ana Copaescu, McGill University Health Centre/Research Institute of the McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04454229
- Sponsor's protocol ID
- PALACE1
- Acronym
- PALACE
- Status last verified
- Mar 2023
- First submitted
- 25 Jun 2020
- Last updated
- 6 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 32176248Devchand 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.
PubMed 30172019Trubiano 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.
PubMed 30547046Copaescu 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.
PubMed 39145980Copaescu 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.
PubMed 37459086Copaescu 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.
PubMed 35940831
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04454229
- Acronym / sponsor ID
- PALACE / PALACE1
- Keywords
- penicillin, Low Risk allergy, direct oral challenge, standard of care, outpatient clinic
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 382 participants (actual)
- Lead sponsor
- Austin HealthOther government
- Study start
- 1 Jul 2021 (actual)
- Primary completion
- 2 Dec 2022 (actual)
- Study completion
- 2 Dec 2022 (actual)
- First posted
- 1 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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).
| Arm | Type | Receives |
|---|---|---|
| Direct oral antibiotic challenge | Experimental | Other: Direct oral penicillin challengeDirect oral antibiotic (penicillin) challenge in patients with PEN-Fast less than 3. |
| Standard of care | Active comparator | Other: Standard of careStandard of care: skin testing and, if negative, oral challenge. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adult patients referred to the outpatient allergy clinic for a penicillin allergy history;
- Willing and able to give consent.
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Direct oral penicillin challengeThe patient will receive a single dose of oral penicillin, following baseline vital signs. | Other | Direct oral antibiotic challenge |
| Standard of careRoutine 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. | Other | Standard of care |
Primary outcome
The difference in the proportion of positive oral challenges (i.e. immune-mediated reaction)
Time frame: up to 48H after oral challenge
12 secondary outcomes
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
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
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
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: 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.
Time frame: Up to 48h after the drug challenge
The proportion of patients that will respect the protocol (protocol compliance)
Time frame: Up to 48h after the drug challenge
Proportion of patient with positive Penicillin Skin Testing
Time frame: Up to 48h after the drug challenge
Proportion of patients with non-immune mediated positive oral provocation
Time frame: Up to 48h after the drug challenge
Proportion of patients with severe adverse reaction - anaphylaxis/death
Time frame: Up to 48h after the drug challenge
Time from randomization to delabelling
Time frame: Up to 48h after the drug challenge
Number of appointments required for Penicillin delabelling
Time frame: Up to 48h after the drug challenge
Assessment with the Pre-Questionnaire and the 6 months follow-up Questionnaire
Time frame: Up to 6 months after the drug challenge
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2023.
- Results publication: PubMed 32176248Trubiano 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.
- Results publication: PubMed 30172019Devchand 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.
- Results publication: PubMed 30547046Trubiano 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.
- Derived from this study: PubMed 39145980Copaescu 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.
- Derived from this study: PubMed 37459086Copaescu 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.
- Derived from this study: PubMed 35940831Copaescu 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.
Related trials for Hypersensitivity, Immediate
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
RecruitingPhase 1
Pilot Study to Identify the Mediators and Inflammatory Cell Surface Receptors Involved in Allergic Airway Inflammation
Asthma
RecruitingObservational study
Blood, Urine, and Tissue Collection for Cutaneous Lymphoma, Eczema, and Atopic Dermatitis Research
Cutaneous T-cell Lymphoma, Sezary Syndrome
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Not yet recruitingPhase 1
A Study of HSK60002 Tablets in Participants With Moderate-to-Severe Atopic Dermatitis
Dermatitis Atopic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Direct oral penicillin challenge in people with Hypersensitivity, Immediate and Hypersensitivity, Delayed, run by Austin Health at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Australia, United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The difference in the proportion of positive oral challenges (i.e. immune-mediated reaction) (time frame: up to 48H after oral challenge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04454229, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2023.