History of IgE Dependent Reaction to a Penicillin ProductPhase 3NCT01818336
Evaluation of Skin Testing Reagents for Penicillin Allergy
A Phase 3 study testing Penicillin skin test kit in people with History of IgE Dependent Reaction to a Penicillin Product, run by AllerQuest LLC at 13 sites in United States.
Trial summary
A self- or parent-reported history of penicillin allergy excludes approximately 10% of the US population from receiving penicillin (Kerr 1994, Kagy, Blaiss 1998, Solensky et al. 2000, Neugut et al. 2001). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- History of IgE Dependent Reaction to a Penicillin Product
- What is being tested?
- Penicillin skin test kit
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 481 participants
- Where
- 13 sitesUnited States
- Study dates
- Dec 2012to Jun 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subject must have provided written, informed consent prior to performance of any procedures.
- Subject can be male or female and must be generally healthy and at least 18 years of age.
- Subject must have a reported history of possible IgE dependent reaction to a penicillin or its semi-synthetic derivatives, including one or more of the following: anaphylaxis, decreased blood pressure and/or diminished consciousness, upper or lower airway obstruction, angioedema, urticaria, and/or generalized pruritic rash.
Who cannot join
- Subject who has exhibited a systemic allergic reaction to previous skin-test administration of PRE-PEN, MDM, or individual penicillin metabolites (benzylpenicillin, benzylpenicilloate, or benzylpenilloate).
- Subject who is pregnant or lactating.
- Subject who has had a respiratory infection within the past 2 weeks or has taken antibiotics of any kind during the past 2 weeks (except for topical antibiotics for acne).
- Subject who has taken an oral H1-antihistamine within 72 hours prior to skin testing.
- Subject who has taken hydroxyzine or doxepin within 7 days prior to skin testing.
- Subject who has had a penicillin reaction, including semisynthetic penicillins, within the last 6 weeks prior to skin testing.
Show all 11Show fewer
- Subject who has received an investigational drug within 30 days prior to skin testing or who plans to participate in a study in which an investigational drug will be administered within the 30 days following skin testing.
- Subjects who have planned hospitalizations or medical or surgical procedures during the 72 hours following the oral amoxicillin challenge.
- Subjects who plan to take any new prescription or over-the-counter medications or herbal supplements during the 72 hours following the oral amoxicillin challenge.
- Subject who has had a previous adverse reaction to penicillin or semisynthetic derivative and subsequently tolerated a penicillin or semisynthetic derivative without an adverse experience.
- Subject who, in the investigator's opinion, has any other social or medical condition (e.g. fever, rash) that may place the subject at increased risk or may confound the interpretation of the study.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Atlanta Allergy and Asthma Clinic
Atlanta, Georgia, 30060
Corvallis Clinic
Corvallis, Oregon, 97330
Allergy & Asthma Care
Germantown, Tennessee, 38138
Alabama Allergy & Asthma Center
Homewood, Alabama, 35209
Fairfield County Allergy, Asthma & Immunology Assoc., Inc.
Norwalk, Connecticut, 06851
Midwest Allergy & Asthma Clinic PC
Omaha, Nebraska, 68130
Northwest Asthma & Allergy Center
Redmond, Washington, 98052
Mayo Clinic
Rochester, Minnesota, 55905
Windom Allergy
Sarasota, Florida, 34233
Washington University Medical School
St Louis, Missouri, 63110
Allergy Associates of Tucson
Tucson, Arizona, 85716
Allergy & Asthma Clinical Research
Walnut Creek, California, 94590
Ct. Asthma & Allergy Center LLC
West Hartford, Connecticut, 06119
About this study
Official title: Confirmatory Study to Examine Negative Predictive Value (NPV) and Safety of Skin Testing With PRE-PEN, a Minor Determinant MIxture (MDM) of Penicillin Antigens, and Amoxicillin Reagent Against an Oral Challenge With Amoxicillin
A self- or parent-reported history of penicillin allergy excludes approximately 10% of the US population from receiving penicillin (Kerr 1994, Kagy, Blaiss 1998, Solensky et al. 2000, Neugut et al. 2001). Yet approximately 80% of patients labeled as allergic to the penicillins can safely take these antibiotics without fear of a life-threatening reaction (Gadde et al. 1993, Macy et al. 1997). The outcomes of this erroneous classification of patients include unnecessary denial of an effective and well-tolerated class of antibiotics, which are often the treatment of choice.
The primary aim of skin testing with the Penicillin Skin Test Kit is to identify subjects at very low risk of developing acute IgE-dependent reactions when given a penicillin or cross-reacting drug. The negative predictive value (NPV) of skin testing is assessed by oral challenge with a penicillin.
Read the detailed description
This is a prospective, open-label investigation of skin testing with the Penicillin Skin Test Kit in subjects at least 18 years of age with a self-reported history of possible IgE-dependent penicillin hypersensitivity.
At screening on Day 1, subjects and their parents/legal guardians (if applicable) will sign the informed consent form/ pediatric assent form. Following consent/assent, demographic information and medical history will be obtained, including prior and current medication use. Subjects will also be asked if they have had a respiratory infection in the past 2 weeks or antibiotics within the past 4 weeks. A physical examination will be performed, along with measurements of vital signs and, in subjects >5 years of age with active asthma, peak expiratory flow rate (PEFR). A urine pregnancy test will be obtained for all female subjects of childbearing potential.
The skin test procedure will first involve puncture testing. Skin test reagents will include the Penicillin Skin Test Kit, histamine (positive control), and sodium chloride (negative control). Subjects who have negative skin puncture test results to any of the drug antigens contained within the Penicillin Skin Test Kit will then undergo intradermal testing in duplicate. Subjects who have a positive reaction to one or more puncture or intradermal tests contained within the Penicillin Skin Test Kit will be discharged from the study. However, subjects with any positive skin test to drug antigens in the Penicillin Skin Test Kit will be asked to return for retesting (puncture and intradermal) in 4 weeks.
Subjects who have negative puncture and intradermal test results will be given the oral amoxicillin challenge, which will be comprised of a single, full oral dose of amoxicillin. The purpose of the oral amoxicillin challenge is to confirm lack of allergy and confirm the NPV (Negative Predictive Value) of skin testing. Subjects will be monitored at the study site for 1 hour following oral amoxicillin challenge and then sent home. The study site will follow-up by telephone with all subjects (or their parents/legal guardians in the case of young children) ≥72 hours after administration of the oral amoxicillin challenge.
Adverse events (AEs) will be recorded from administration of the Penicillin Skin Test throughout the 3-day study period as spontaneously reported by subjects or observed by the site staff.
Two normal subjects (i.e., no history of penicillin allergy) will be skin tested at each site to provide data on skin test specificity.
- Being tested
- Penicillin skin test kit
- Keywords
- penicillin allergy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Penicillin skin test kitDrug
Also called PRE-PEN (benzylpenicilloyl polylysine), MDM (minor determinant mixture of penicillins), benzylpenicillin, benzylpenicilloate
Allergy skin testing is done by puncture and intradermal. If all tests negative, subjects receive an oral amoxicillin challenge.
| Study group | Role | What they receive |
|---|---|---|
| all subjects | Experimental | Intervention: Penicillin skin test kit
Subjects with negative intradermal tests will be given single oral amoxicillin challenge dose and followed for 72 hours for IgE dependent reactions. Receives: Drug: Penicillin skin test kit |
What is being measured
The primary outcome is the main question the study is designed to answer.
Negative Predictive Value
The primary endpoint was the negative predictive value (NPV), which was estimated as p = percentage of n history-positive subjects with negative skin tests from the Penicillin Allergy Skin Test Kit (as confirmed with an overall negative result for the skin puncture/intradermal testing) who do not experience an IgE-dependent hypersensitivity reaction within 72 hours of the oral amoxicillin challenge.
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2013 (estimated)
- Study startDec 2012
- Primary completionJun 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for History of IgE Dependent Reaction to a Penicillin ProductStudies 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 3
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 481 participants (actual)
Sponsor and investigators
- Lead sponsor
- AllerQuest LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- N. Franklin Adkinson, Jr., MD, Study director, AllerQuest LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01818336
- Sponsor's protocol ID
- AQ-2010-001
- Other IDs
- AllerQuest LLC
- Status last verified
- Nov 2016
- First submitted
- 11 Mar 2013
- Last updated
- 4 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Confirmatory Study to Examine Negative Predictive Value (NPV) and Safety of Skin Testing With PRE-PEN, a Minor Determinant MIxture (MDM) of Penicillin Antigens, and Amoxicillin Reagent Against an Oral Challenge With Amoxicillin
- ClinicalTrials.gov ID
- NCT01818336
- Acronym / sponsor ID
- AQ-2010-001
- Keywords
- penicillin allergy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 481 participants (actual)
- Lead sponsor
- AllerQuest LLCIndustry (pharma, biotech, devices)
- Study start
- Dec 2012
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 26 Mar 2013 (estimated)
- Results
- Posted 4 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A self- or parent-reported history of penicillin allergy excludes approximately 10% of the US population from receiving penicillin (Kerr 1994, Kagy, Blaiss 1998, Solensky et al. 2000, Neugut et al. 2001). Yet approximately 80% of patients labeled as allergic to the penicillins can safely take these antibiotics without fear of a life-threatening reaction (Gadde et al. 1993, Macy et al. 1997). The outcomes of this erroneous classification of patients include unnecessary denial of an effective and well-tolerated class of antibiotics, which are often the treatment of choice.
The primary aim of skin testing with the Penicillin Skin Test Kit is to identify subjects at very low risk of developing acute IgE-dependent reactions when given a penicillin or cross-reacting drug. The negative predictive value (NPV) of skin testing is assessed by oral challenge with a penicillin.
Detailed description
This is a prospective, open-label investigation of skin testing with the Penicillin Skin Test Kit in subjects at least 18 years of age with a self-reported history of possible IgE-dependent penicillin hypersensitivity.
At screening on Day 1, subjects and their parents/legal guardians (if applicable) will sign the informed consent form/ pediatric assent form. Following consent/assent, demographic information and medical history will be obtained, including prior and current medication use. Subjects will also be asked if they have had a respiratory infection in the past 2 weeks or antibiotics within the past 4 weeks. A physical examination will be performed, along with measurements of vital signs and, in subjects >5 years of age with active asthma, peak expiratory flow rate (PEFR). A urine pregnancy test will be obtained for all female subjects of childbearing potential.
The skin test procedure will first involve puncture testing. Skin test reagents will include the Penicillin Skin Test Kit, histamine (positive control), and sodium chloride (negative control). Subjects who have negative skin puncture test results to any of the drug antigens contained within the Penicillin Skin Test Kit will then undergo intradermal testing in duplicate. Subjects who have a positive reaction to one or more puncture or intradermal tests contained within the Penicillin Skin Test Kit will be discharged from the study. However, subjects with any positive skin test to drug antigens in the Penicillin Skin Test Kit will be asked to return for retesting (puncture and intradermal) in 4 weeks.
Subjects who have negative puncture and intradermal test results will be given the oral amoxicillin challenge, which will be comprised of a single, full oral dose of amoxicillin. The purpose of the oral amoxicillin challenge is to confirm lack of allergy and confirm the NPV (Negative Predictive Value) of skin testing. Subjects will be monitored at the study site for 1 hour following oral amoxicillin challenge and then sent home. The study site will follow-up by telephone with all subjects (or their parents/legal guardians in the case of young children) ≥72 hours after administration of the oral amoxicillin challenge.
Adverse events (AEs) will be recorded from administration of the Penicillin Skin Test throughout the 3-day study period as spontaneously reported by subjects or observed by the site staff.
Two normal subjects (i.e., no history of penicillin allergy) will be skin tested at each site to provide data on skin test specificity.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| all subjects | Experimental | Drug: Penicillin skin test kitIntervention: Penicillin skin test kit Subjects with negative intradermal tests will be given single oral amoxicillin challenge dose and followed for 72 hours for IgE dependent reactions. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Subject must have provided written, informed consent prior to performance of any procedures.
- Subject can be male or female and must be generally healthy and at least 18 years of age.
- Subject must have a reported history of possible IgE dependent reaction to a penicillin or its semi-synthetic derivatives, including one or more of the following: anaphylaxis, decreased blood pressure and/or diminished consciousness, upper or lower airway obstruction, angioedema, urticaria, and/or generalized pruritic rash.
Key exclusion criteria (11 listed)
- Subject who has exhibited a systemic allergic reaction to previous skin-test administration of PRE-PEN, MDM, or individual penicillin metabolites (benzylpenicillin, benzylpenicilloate, or benzylpenilloate).
- Subject who is pregnant or lactating.
- Subject who has had a respiratory infection within the past 2 weeks or has taken antibiotics of any kind during the past 2 weeks (except for topical antibiotics for acne).
- Subject who has taken an oral H1-antihistamine within 72 hours prior to skin testing.
- Subject who has taken hydroxyzine or doxepin within 7 days prior to skin testing.
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 |
|---|---|---|
| Penicillin skin test kitAlso: PRE-PEN (benzylpenicilloyl polylysine), MDM (minor determinant mixture of penicillins), benzylpenicillin, benzylpenicilloateAllergy skin testing is done by puncture and intradermal. If all tests negative, subjects receive an oral amoxicillin challenge. | Drug | all subjects |
Primary outcome
Negative Predictive Value
Time frame: 72 hours
The primary endpoint was the negative predictive value (NPV), which was estimated as p = percentage of n history-positive subjects with negative skin tests from the Penicillin Allergy Skin Test Kit (as confirmed with an overall negative result for the skin puncture/intradermal testing) who do not experience an IgE-dependent hypersensitivity reaction within 72 hours of the oral amoxicillin challenge.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.
N. Franklin Adkinson, Jr., MD study director
AllerQuest LLC
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Penicillin skin test kit in people with History of IgE Dependent Reaction to a Penicillin Product, run by AllerQuest LLC at 13 sites in United States.
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 11 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 4 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Negative Predictive Value (time frame: 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Jan 2017.