Drug HypersensitivityPhase 1NCT03158831
Drug Challenges Without Prior Skin Testing
A Phase 1 study of Drug Hypersensitivity and Penicillin Allergy, run by Montefiore Medical Center at 1 site in United States.
Trial summary
The investigators are conducting a prospective study to determine the safety and outcomes of placebo-controlled graded drug challenges without prior skin testing in patients with a low-risk history of antibiotic hypersensitivity reaction based on history alone. Read more about this study
- Who is it for?
- Ages 7 years and olderHealthy volunteers can take part
- Conditions the study is for
- Drug Hypersensitivity, Penicillin Allergy, Antibiotic Allergy
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 166 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jan 2016to 1 Oct 2021
- Phase
- Phase 1
- 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 7 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- All patients seven years of age or older who have a low-risk, non-life-threatening history of adverse reaction to an antibiotic.
Who cannot join
- Patients under the age of seven.
- Pregnant patients.
- Patients with a history of a drug reaction that is high-risk and life-threatening including life-threatening angioedema, bronchospasm, or anaphylactic shock or a history of severe non-IgE-mediated reactions including serum sickness, Stevens-Johnson syndrome, toxic epidermal necrolysis, interstitial nephritis, hepatitis, hemolytic anemia, DRESS, skin and/or oral blisters, hypersensitivity vasculitis, pneumonitis, or pulmonary fibrosis.
- Patients who have taken antihistamines within 3 days of the drug challenge.
Trial locations and contacts
1 site in 1 country.
United States1 site
Montefiore Medical Center
The Bronx, New York, 10461
About this study
The investigators are conducting a prospective study to determine the safety and outcomes of placebo-controlled graded drug challenges without prior skin testing in patients with a low-risk history of antibiotic hypersensitivity reaction based on history alone. The investigators hypothesize that the rate of reaction to graded drug challenges without prior skin testing in patients with a low-risk history of drug hypersensitivity reaction based on history alone will not be meaningfully more than the rate of reaction to placebo. The investigators hypothesize that the rate of adverse reactions to drug challenges without prior skin testing will not be meaningfully more than the rate of adverse reactions with prior skin testing as was observed in the investigators' historical clinic cohort.
Read the detailed description
Graded drug challenges are the gold standard to exclude an immediate hypersensitivity reaction in patients with a low likelihood of drug allergy and are considered standard of care. Patients who tolerate a graded challenge are deemed to not be allergic to the drug and are not at increased risk for future reactions compared with the general population. Prior studies of graded challenges in appropriately selected patients have demonstrated low reaction rates with symptoms that were mainly mild and subjective in nature. The investigators are conducting a prospective study to determine the safety and outcomes of placebo-controlled graded drug challenges without prior skin testing in patients with a low-risk history of antibiotic hypersensitivity reaction based on history alone. Skin testing requires a separate visit and is, therefore, more time-consuming and costly than performing a graded challenge without skin testing. The investigators believe that they can determine if patients are at low-risk to react to an antibiotic based on a detailed history and, therefore, do not require skin testing prior to a challenge. Given the majority of symptoms to graded drug challenges reported in prior studies were mild and subjective, the investigators hypothesize that the rate of reaction to graded drug challenges without prior skin testing in patients with a low-risk history of drug hypersensitivity reaction based on history alone will not be meaningfully more than the rate of reaction to placebo. The investigators hypothesize that the rate of adverse reactions to drug challenges without prior skin testing will be not meaningfully more than the rate of adverse reactions with prior skin testing as was observed in the investigators' historical clinic cohort. All patients age 7 years or older with a history of a non-life-threatening reaction to an antibiotic are eligible to participate in a placebo-controlled graded drug challenge. The challenge is comprised of placebo followed by 30 minutes of observation, 1/10th of the treatment dose of the antibiotic the patient reported a reaction followed by 30 minutes of observation, and the full dose of the antibiotic followed by 1 hour of observation. All patients will be contacted via telephone within one month of a negative challenge to determine whether they experienced a delayed reaction. All patients will also be contacted via telephone within one year of a negative challenge to determine if they have safely taken the challenge drug.
- Being tested
- Placebo-Controlled Graded Drug Challenge
- Keywords
- Drug Allergy, Penicillin Allergy, Antibiotic Allergy, Graded Drug Challenge
- Medical subject headings
- Drug Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo-Controlled Graded Drug ChallengeDrug
All patients receive a placebo followed by 30 minutes of observation. Patients then receive 1/10 of the treatment dose of the challenge drug followed by 30 minutes of observation. If no reaction, they will then receive a full dose of their challenge drug followed by 1 hour of observation. If they do not experience any reactions, they are deemed not to be allergic. All patients are asked to monitor for delayed reactions after the challenge. Patients are also called within 1 month of the challenge to determine if any delayed reactions occurred. Patients are called again within 1 year of the challenge to determine if they have subsequently taken the challenge drug and experienced any reactions.
| Study group | Role | What they receive |
|---|---|---|
| Placebo-Controlled Graded Drug Challenge | Other | This is a single arm study. All patients will receive a placebo prior to a graded drug challenge. Each patient serves as his/her own control. Receives: Drug: Placebo-Controlled Graded Drug Challenge |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of unexpected reaction to graded drug challenges without prior skin testing compared to rate of unexpected reaction to graded drug challenges with prior skin testing.
Determine the rate of unexpected reaction to a graded drug challenge without prior skin testing versus the rate of reaction to a graded drug challenge with prior skin testing in the investigators' historical cohort (data on this cohort has already been published: Iammatteo M, Ferastraoaru D, Koransky R, Alvarez-Arango S, Thota N, Akenroye A, Jerschow E. Identifying Allergic Drug Reactions Through Placebo-Controlled Graded Challenges. J Allergy Clin Immunol Pract. 2017 May - Jun;5(3):711-717.e2.).
Measured: It is anticipated the study will take 2 years to enroll 200 patients with subsequent data comparison.
Secondary outcomes (2)
Rate of unexpected reaction to graded drug challenges versus placebos
Determine the rate of unexpected reaction to graded drug challenges without prior skin tests versus the rate of unexpected reaction to placebos in patients with a low-risk history of drug hypersensitivity reaction based on history alone.
Measured: Patients are monitored for 1 hour after completion of their drug challenge.
Rate of unexpected delayed reaction to graded drug challenges
Determine the rate of unexpected delayed reaction to graded challenges
Measured: Patients are called within 1 month of their challenge to determine if they had any delayed reactions.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2017
- Study start13 Jan 2016
- Primary completion1 Oct 2021
- Study completion1 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Drug HypersensitivityStudies 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 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective interventional study whereby each eligible patient undergoes a placebo-controlled graded challenge. Each patient receives a placebo prior to undergoing a graded challenge to 1/10 the treatment dose of the challenge drug followed by a full treatment dose of the challenge drug.
- Masking
- None (open label)
- Enrolment
- 166 participants (actual)
Sponsor and investigators
- Lead sponsor
- Montefiore Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Elina Jerschow, Montefiore Medical Center
- Investigators
- Elina Jerschow, MD, MSc, Principal investigator, Montefiore Medical Center/Albert Einstein College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03158831
- Sponsor's protocol ID
- 2015-5610
- Status last verified
- Nov 2021
- First submitted
- 11 May 2017
- Last updated
- 16 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: We do not plan to make IPD available to other researchers.
Publications
Iammatteo M, Ferastraoaru D, Koransky R, Alvarez-Arango S, Thota N, Akenroye A, Jerschow E. Identifying Allergic Drug Reactions Through Placebo-Controlled Graded Challenges. J Allergy Clin Immunol Pract. 2017 May-Jun;5(3):711-717.e2. doi: 10.1016/j.jaip.2016.09.041. Epub 2016 Nov 23.
PubMed 27888028Iammatteo M, Blumenthal KG, Saff R, Long AA, Banerji A. Safety and outcomes of test doses for the evaluation of adverse drug reactions: a 5-year retrospective review. J Allergy Clin Immunol Pract. 2014 Nov-Dec;2(6):768-74. doi: 10.1016/j.jaip.2014.08.001. Epub 2014 Sep 10.
PubMed 25439369Macy E, Romano A, Khan D. Practical Management of Antibiotic Hypersensitivity in 2017. J Allergy Clin Immunol Pract. 2017 May-Jun;5(3):577-586. doi: 10.1016/j.jaip.2017.02.014. Epub 2017 Mar 29.
PubMed 28365277Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273. doi: 10.1016/j.anai.2010.08.002.
PubMed 20934625
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Drug Challenges Without Prior Skin Testing
- ClinicalTrials.gov ID
- NCT03158831
- Acronym / sponsor ID
- 2015-5610
- Keywords
- Drug Allergy, Penicillin Allergy, Antibiotic Allergy, Graded Drug Challenge
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 166 participants (actual)
- Lead sponsor
- Montefiore Medical CenterUniversity, hospital or other
- Study start
- 13 Jan 2016 (actual)
- Primary completion
- 1 Oct 2021 (actual)
- Study completion
- 1 Oct 2021 (actual)
- First posted
- 18 May 2017 (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 investigators are conducting a prospective study to determine the safety and outcomes of placebo-controlled graded drug challenges without prior skin testing in patients with a low-risk history of antibiotic hypersensitivity reaction based on history alone. The investigators hypothesize that the rate of reaction to graded drug challenges without prior skin testing in patients with a low-risk history of drug hypersensitivity reaction based on history alone will not be meaningfully more than the rate of reaction to placebo. The investigators hypothesize that the rate of adverse reactions to drug challenges without prior skin testing will not be meaningfully more than the rate of adverse reactions with prior skin testing as was observed in the investigators' historical clinic cohort.
Detailed description
Graded drug challenges are the gold standard to exclude an immediate hypersensitivity reaction in patients with a low likelihood of drug allergy and are considered standard of care. Patients who tolerate a graded challenge are deemed to not be allergic to the drug and are not at increased risk for future reactions compared with the general population. Prior studies of graded challenges in appropriately selected patients have demonstrated low reaction rates with symptoms that were mainly mild and subjective in nature. The investigators are conducting a prospective study to determine the safety and outcomes of placebo-controlled graded drug challenges without prior skin testing in patients with a low-risk history of antibiotic hypersensitivity reaction based on history alone. Skin testing requires a separate visit and is, therefore, more time-consuming and costly than performing a graded challenge without skin testing. The investigators believe that they can determine if patients are at low-risk to react to an antibiotic based on a detailed history and, therefore, do not require skin testing prior to a challenge. Given the majority of symptoms to graded drug challenges reported in prior studies were mild and subjective, the investigators hypothesize that the rate of reaction to graded drug challenges without prior skin testing in patients with a low-risk history of drug hypersensitivity reaction based on history alone will not be meaningfully more than the rate of reaction to placebo. The investigators hypothesize that the rate of adverse reactions to drug challenges without prior skin testing will be not meaningfully more than the rate of adverse reactions with prior skin testing as was observed in the investigators' historical clinic cohort. All patients age 7 years or older with a history of a non-life-threatening reaction to an antibiotic are eligible to participate in a placebo-controlled graded drug challenge. The challenge is comprised of placebo followed by 30 minutes of observation, 1/10th of the treatment dose of the antibiotic the patient reported a reaction followed by 30 minutes of observation, and the full dose of the antibiotic followed by 1 hour of observation. All patients will be contacted via telephone within one month of a negative challenge to determine whether they experienced a delayed reaction. All patients will also be contacted via telephone within one year of a negative challenge to determine if they have safely taken the challenge drug.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective interventional study whereby each eligible patient undergoes a placebo-controlled graded challenge. Each patient receives a placebo prior to undergoing a graded challenge to 1/10 the treatment dose of the challenge drug followed by a full treatment dose of the challenge drug.
| Arm | Type | Receives |
|---|---|---|
| Placebo-Controlled Graded Drug Challenge | Other | Drug: Placebo-Controlled Graded Drug ChallengeThis is a single arm study. All patients will receive a placebo prior to a graded drug challenge. Each patient serves as his/her own control. |
Who may qualify
- Ages
- 7 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- All patients seven years of age or older who have a low-risk, non-life-threatening history of adverse reaction to an antibiotic.
Key exclusion criteria (4 listed)
- Patients under the age of seven.
- Pregnant patients.
- Patients with a history of a drug reaction that is high-risk and life-threatening including life-threatening angioedema, bronchospasm, or anaphylactic shock or a history of severe non-IgE-mediated reactions including serum sickness, Stevens-Johnson syndrome, toxic epidermal necrolysis, interstitial nephritis, hepatitis, hemolytic anemia, DRESS, skin and/or oral blisters, hypersensitivity vasculitis, pneumonitis, or pulmonary fibrosis.
- Patients who have taken antihistamines within 3 days of the drug challenge.
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 |
|---|---|---|
| Placebo-Controlled Graded Drug ChallengeAll patients receive a placebo followed by 30 minutes of observation. Patients then receive 1/10 of the treatment dose of the challenge drug followed by 30 minutes of observation. If no reaction, they will then receive a full dose of their challenge drug followed by 1 hour of observation. If they do not experience any reactions, they are deemed not to be allergic. All patients are asked to monitor for delayed reactions after the challenge. Patients are also called within 1 month of the challenge to determine if any delayed reactions occurred. Patients are called again within 1 year of the challenge to determine if they have subsequently taken the challenge drug and experienced any reactions. | Drug | Placebo-Controlled Graded Drug Challenge |
Primary outcome
Rate of unexpected reaction to graded drug challenges without prior skin testing compared to rate of unexpected reaction to graded drug challenges with prior skin testing.
Time frame: It is anticipated the study will take 2 years to enroll 200 patients with subsequent data comparison.
Determine the rate of unexpected reaction to a graded drug challenge without prior skin testing versus the rate of reaction to a graded drug challenge with prior skin testing in the investigators' historical cohort (data on this cohort has already been published: Iammatteo M, Ferastraoaru D, Koransky R, Alvarez-Arango S, Thota N, Akenroye A, Jerschow E. Identifying Allergic Drug Reactions Through Placebo-Controlled Graded Challenges. J Allergy Clin Immunol Pract. 2017 May - Jun;5(3):711-717.e2.).
2 secondary outcomes
Rate of unexpected reaction to graded drug challenges versus placebos
Time frame: Patients are monitored for 1 hour after completion of their drug challenge.
Rate of unexpected delayed reaction to graded drug challenges
Time frame: Patients are called within 1 month of their challenge to determine if they had any delayed reactions.
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 16 Nov 2021.
- Background: PubMed 27888028Iammatteo M, Ferastraoaru D, Koransky R, Alvarez-Arango S, Thota N, Akenroye A, Jerschow E. Identifying Allergic Drug Reactions Through Placebo-Controlled Graded Challenges. J Allergy Clin Immunol Pract. 2017 May-Jun;5(3):711-717.e2. doi: 10.1016/j.jaip.2016.09.041. Epub 2016 Nov 23.
- Background: PubMed 25439369Iammatteo M, Blumenthal KG, Saff R, Long AA, Banerji A. Safety and outcomes of test doses for the evaluation of adverse drug reactions: a 5-year retrospective review. J Allergy Clin Immunol Pract. 2014 Nov-Dec;2(6):768-74. doi: 10.1016/j.jaip.2014.08.001. Epub 2014 Sep 10.
- Background: PubMed 28365277Macy E, Romano A, Khan D. Practical Management of Antibiotic Hypersensitivity in 2017. J Allergy Clin Immunol Pract. 2017 May-Jun;5(3):577-586. doi: 10.1016/j.jaip.2017.02.014. Epub 2017 Mar 29.
- Background: PubMed 20934625Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273. doi: 10.1016/j.anai.2010.08.002.
- Individual participant dataSharing planned: No. We do not plan to make IPD available to other researchers.
Related trials for Drug Hypersensitivity
RecruitingObservational study
Blood Sampling for Research Related to Sickle Cell Disease
Sickle Cell Trait, Sickle Cell Disease
RecruitingPhase 1
A Study to Evaluate the Safety and Drug Levels of ASP5541 in Chinese Participants With Prostate Cancer
Prostate Cancer, Metastatic Castration-Resistant Prostate Cancer
Recruiting
Organ Culture for Endocrine Resistant Next Line: A Treatment Selection Study in Metastatic Breast Cancer
Metastatic Breast Cancer, Hormon Receptor Positive Breast Cancer
Active, not recruitingPhase 2
A Study To Learn About Two Study Medicines (PF-07275315 And PF-07264660) In People Who Have Moderate To Severe Atopic Dermatitis
Atopic Dermatitis
RecruitingObservational study
Post-market Safety Study of LUMISIGHT
Hypersensitivity Reactions
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.
Elina Jerschow, MD, MSc principal investigator
Montefiore Medical Center/Albert Einstein College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study of Drug Hypersensitivity and Penicillin Allergy, run by Montefiore Medical Center at 1 site 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 1 inclusion and 4 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 16 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Rate of unexpected reaction to graded drug challenges without prior skin testing compared to rate of unexpected reaction to graded drug challenges with prior skin testing. (time frame: It is anticipated the study will take 2 years to enroll 200 patients with subsequent data comparison.). 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 NCT03158831, which also lists 4 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 16 Nov 2021.