Penicillin AllergyNCT06755281
Risk-stratified Testing for Safe Removal of Penicillin Allergy Labels
A study testing Direct Oral challenge in people with Penicillin Allergy and Hypersensitivity, Immediate, run by Deniz Göcebe at 2 sites in Germany.
Trial summary
The aim of this clinical trial is to analyze the negative predictive capacity and safety of risk-stratified direct drug provocation tests for patients with self-reported penicillin allergies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Penicillin Allergy, Hypersensitivity, Immediate, Hypersensitivity, Delayed
- What is being tested?
- Direct Oral challenge
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 2 sitesGermany
- Study dates
- 8 Jan 2025to Feb 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 outpatients or inpatients with a penicillin allergy label
- Willing and able to give consent.
- PEN-FAST score of 0-2 points
Who cannot join
- Age <18 years
- Concurrent immunosuppressive therapy with 20 mg of prednisolone per day or steroid equivalent
- Concurrent antihistamine therapy
- Pregnancy
- Significantly impaired general condition
- Unstable or therapeutically inadequately controlled bronchial asthma
Show all 10Show fewer
- History of stem cell transplantation
- History of acute interstitial nephritis
- Chronic urticaria
- Mastocytosis
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Knut Schäkel, MD contact
Germany2 sites, 2 recruiting
- Recruiting
University Hospital Heidelberg, Dermatology
Heidelberg, Baden-Wurttemberg, 69120
Deniz Göcebe, MD, +4962215639539, Deniz.Goecebe@med.uni-heidelberg.de
Deniz Göcebe
- Recruiting
University Hospital Heidelberg, Division of Infectious Diseases and Tropical Medicine
Heidelberg, Baden-Wurttemberg, 69120
Elham Khatamzas, MD, +4962215622999, Elham.Khatamzas@med.uni-heidelberg.de
Elham Khatamzas, MD
About this study
The aim of this clinical trial is to analyze the negative predictive capacity and safety of risk-stratified direct drug provocation tests for patients with self-reported penicillin allergies. Patients reporting immediate or delayed penicillin allergies and defined as low-risk by the PEN-FAST score will receive drug provocation tests without prior skin testing.
Read the detailed description
The PEN-FAST clinical decision rule is an internationally validated scoring system (0-5 points) that identifies low-risk patients (= a score of 0-2 points) with self-reported penicillin allergies with a negative predictive value (NPV) of over 95%. Performing direct drug provocation tests without prior skin testing on these low-risk patients was shown to be non-inferior in terms of safety and prediction of immediate allergic reactions. However, several studies have questioned the negative predictive capacity of the PEN-FAST score. In these studies, misclassifications of the PEN-FAST score were mainly based on positive skin test findings that can show false-positive results.
This study aims to validate the NPV and safety of direct drug provocation tests using the PEN-FAST score.
Participants with a PEN-FAST score of 0-2 points will directly receive a two-dose challenge (50%-50%) or single challenge (100%) with the culprit penicillin and will be monitored for at least 4 hours. No skin tests will be performed prior to the drug provocation test. Patients will be instructed to contact the hospital after the drug provocation test to monitor any delayed allergic reactions.
The outcomes will be compared to those of patients with a PEN-FAST score of 0-2 points who do not wish to skip the skin tests and who will, in parallel, receive the standard-of-care testing.
Currently, this study is approved as a single-site study.
- Conditions
- Penicillin Allergy, Hypersensitivity, Immediate, Hypersensitivity, Delayed, Hypersensitivity Response
- Being tested
- Direct Oral challenge, standard of care
- Keywords
- PEN-FAST, penicillin allergy, allergy delabeling
- 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 challengeOther
Patients will receive a 1-step or 2-step challenge with the suspected penicillin and will be monitored for any allergic reaction within the first four hours. Patients will be instructed to contact the hospital after the drug provocation test to inquire delayed allergic reactions.
standard of careOther
The patient will receive skin prick test and patch test (if a delayed allergy is suspected). Allergen-specific IgE will be measured. If all negative, drug provocation tets will be performed identical to the experimental group.
| Study group | Role | What they receive |
|---|---|---|
| Direct drug provocation test | Experimental | Not described Receives: Other: Direct Oral challenge |
| Standard of care | Active comparator | Standard of care Skin testing and measurement of allergen-specific IgE, if negative, drug provocation test. 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 patients with any positive finding in skin tests, allergen-specific IgE or drug provocation test between the two groups
Percentage of subjects that retain their allergy label as they show at least one positive finding in skin tests, allergen-specific IgE or drug provocation test.
Measured: 7 days
Secondary outcomes (11)
Negative predictive capacity of skin tests and allergen-specific IgE
Negative predictive values of each test alone and combined
Measured: 7 days
Analysis of medical and allergic history
(supposed) allergic symptoms
Measured: 1 day
Penicillin allergy label
Identification of culprit penicillin
Measured: 1 day
Analysis of demographic data
Age, sex
Measured: 1 day
Analysis of adverse reactions
Detailed analysis of any (supposed) allergic reactions following drug provocation test
Measured: 7 days
Analysis of medical and allergic history
year of (supposed) allergic reaction
Measured: One day
Analysis of medical and allergic history
time between administration and (supposed) allergic reaction
Measured: One day
Analysis of medical and allergic history
treatment required for (supposed) allergic reaction
Measured: One day
Analysis of medical and allergic history
current medication
Measured: One day
Analysis of internal hospital risk stratification system
Measurement of score of internal hospital risk stratification system
Measured: One day
Analysis of medical and allergic history
(supposed) allergic symptoms
Measured: One day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jan 2025
- Study start8 Jan 2025
- Primary completionDec 2026 (estimated)
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Penicillin AllergyStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Deniz Göcebe
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Deniz Göcebe, University Hospital Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06755281
- Sponsor's protocol ID
- S-656/2024
- Status last verified
- Apr 2025
- First submitted
- 22 Dec 2024
- Last updated
- 10 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in the article that is planned to be published, after deidentification.
Publications
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.
PubMed 37459086Trubiano 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 32176248
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risk-stratified Testing for Safe Removal of Penicillin Allergy Labels
- ClinicalTrials.gov ID
- NCT06755281
- Acronym / sponsor ID
- S-656/2024
- Conditions
- Penicillin Allergy, Hypersensitivity, Immediate, Hypersensitivity, Delayed, Hypersensitivity Response
- Keywords
- PEN-FAST, penicillin allergy, allergy delabeling
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Deniz GöcebeUniversity, hospital or other
- Study start
- 8 Jan 2025 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Feb 2027 (estimated)
- First posted
- 1 Jan 2025 (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.
The aim of this clinical trial is to analyze the negative predictive capacity and safety of risk-stratified direct drug provocation tests for patients with self-reported penicillin allergies. Patients reporting immediate or delayed penicillin allergies and defined as low-risk by the PEN-FAST score will receive drug provocation tests without prior skin testing.
Detailed description
The PEN-FAST clinical decision rule is an internationally validated scoring system (0-5 points) that identifies low-risk patients (= a score of 0-2 points) with self-reported penicillin allergies with a negative predictive value (NPV) of over 95%. Performing direct drug provocation tests without prior skin testing on these low-risk patients was shown to be non-inferior in terms of safety and prediction of immediate allergic reactions. However, several studies have questioned the negative predictive capacity of the PEN-FAST score. In these studies, misclassifications of the PEN-FAST score were mainly based on positive skin test findings that can show false-positive results.
This study aims to validate the NPV and safety of direct drug provocation tests using the PEN-FAST score.
Participants with a PEN-FAST score of 0-2 points will directly receive a two-dose challenge (50%-50%) or single challenge (100%) with the culprit penicillin and will be monitored for at least 4 hours. No skin tests will be performed prior to the drug provocation test. Patients will be instructed to contact the hospital after the drug provocation test to monitor any delayed allergic reactions.
The outcomes will be compared to those of patients with a PEN-FAST score of 0-2 points who do not wish to skip the skin tests and who will, in parallel, receive the standard-of-care testing.
Currently, this study is approved as a single-site study.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Direct drug provocation test | Experimental | Other: Direct Oral challenge |
| Standard of care | Active comparator | Other: standard of careStandard of care Skin testing and measurement of allergen-specific IgE, if negative, drug provocation test. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult outpatients or inpatients with a penicillin allergy label
- Willing and able to give consent.
- PEN-FAST score of 0-2 points
Key exclusion criteria (10 listed)
- Age <18 years
- Concurrent immunosuppressive therapy with 20 mg of prednisolone per day or steroid equivalent
- Concurrent antihistamine therapy
- Pregnancy
- Significantly impaired general condition
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 challengePatients will receive a 1-step or 2-step challenge with the suspected penicillin and will be monitored for any allergic reaction within the first four hours. Patients will be instructed to contact the hospital after the drug provocation test to inquire delayed allergic reactions. | Other | Direct drug provocation test |
| standard of careThe patient will receive skin prick test and patch test (if a delayed allergy is suspected). Allergen-specific IgE will be measured. If all negative, drug provocation tets will be performed identical to the experimental group. | Other | Standard of care |
Primary outcome
The difference in the proportion of patients with any positive finding in skin tests, allergen-specific IgE or drug provocation test between the two groups
Time frame: 7 days
Percentage of subjects that retain their allergy label as they show at least one positive finding in skin tests, allergen-specific IgE or drug provocation test.
11 secondary outcomes
Negative predictive capacity of skin tests and allergen-specific IgE
Time frame: 7 days
Analysis of medical and allergic history
Time frame: 1 day
Penicillin allergy label
Time frame: 1 day
Analysis of demographic data
Time frame: 1 day
Analysis of adverse reactions
Time frame: 7 days
Analysis of medical and allergic history
Time frame: One day
Analysis of medical and allergic history
Time frame: One day
Analysis of medical and allergic history
Time frame: One day
Analysis of medical and allergic history
Time frame: One day
Analysis of internal hospital risk stratification system
Time frame: One day
Analysis of medical and allergic history
Time frame: One day
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2025.
- Results publication: 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.
- 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.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in the article that is planned to be published, after deidentification.
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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.
Knut Schäkel, MD contact
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Direct Oral challenge in people with Penicillin Allergy and Hypersensitivity, Immediate, run by Deniz Göcebe at 2 sites in Germany.
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 3 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 10 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Deniz Göcebe, MD (+4962215639539, Deniz.Goecebe@med.uni-heidelberg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The difference in the proportion of patients with any positive finding in skin tests, allergen-specific IgE or drug provocation test between the two groups (time frame: 7 days). 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 NCT06755281, which also lists 2 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 10 Apr 2025.