Optimizing the Diagnostic Approach to Cephalosporin Allergy Testing
DACAT
2 other identifiers
interventional
300
1 country
6
Brief Summary
Cephalosporin antibiotics are commonly used but can result in allergic reactions and anaphylaxis. There is no clear diagnostic approach for cephalosporin-allergic patients, and guidance for the use of other antibiotics in allergic patients is based on side chain chemical similarity and limited skin testing evidence. This project includes a clinical trial and mechanistic studies to optimize the approach to cephalosporin allergy and advance future diagnostics.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2025
Typical duration for phase_2
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 17, 2024
CompletedFirst Posted
Study publicly available on registry
May 9, 2024
CompletedStudy Start
First participant enrolled
May 5, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2028
March 19, 2026
January 1, 2026
3.2 years
April 17, 2024
March 17, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Proportion of participants with confirmed culprit cephalosporin allergy
Placebo-controlled drug challenges will be used to confirm or disprove participant's cephalosporin allergies, and the proportion of included participants with confirmed allergies will be measured.
Up to 7 weeks
Cephalosporin skin test sensitivity and specificity
Challenge results will be used as a reference standard to determine the sensitivity and specificity of cephalosporin skin testing.
Up to 7 weeks
Proportion of cross-reactivity to other cephalosporins in confirmed-allergic subjects
The proportion of participants with confirmed cross-reactivity to dissimilar/similar cephalosporins than their culprit will be determined.
Up to 7 weeks
Secondary Outcomes (7)
Culprit cephalosporin skin test diagnostic characteristics
Up to 7 weeks
Cephalosporin skin test diagnostic characteristic performance differences between risk groups
Up to 7 weeks
Association between patient demographics and confirmed cephalosporin allergy
Up to 7 weeks
Association between patient allergy history and confirmed cephalosporin allergy
Up to 7 weeks
Proportion of nocebo responders
Up to 7 weeks
- +2 more secondary outcomes
Other Outcomes (11)
Prevalence of nocebo response
Up to 7 weeks
Graded severity of nocebo response reactions
Up to 7 weeks
Cephalosporin skin test clinical statistics
Up to 7 weeks
- +8 more other outcomes
Study Arms (2)
Similar cephalosporin first
EXPERIMENTALIn visit 2, confirmed-allergic subjects will have a double-blind placebo-controlled drug challenge to a similar side chain cephalosporin, followed by a double-blind placebo-controlled challenge to a dissimilar side chain cephalosporin in visit 3. The randomization of which cephalosporin (similar or dissimilar side chain) is challenged in visits 2 and 3 differentiates the two arms.
Dissimilar cephalosporin first
EXPERIMENTALIn visit 2, confirmed-allergic subjects will have a double-blind placebo-controlled drug challenge to a dissimilar side chain cephalosporin, followed by a double-blind placebo-controlled challenge to a similar side chain cephalosporin in visit 3. The randomization of which cephalosporin (similar or dissimilar side chain) is challenged in visits 2 and 3 differentiates the two arms.
Interventions
Percutaneous and intradermal skin testing will be performed in all participants. Concentrations for percutaneous testing; cefazolin (330 mg/ml), cefuroxime (90 mg/ml), ceftazidime (100 mg/ml), ceftriaxone (100 mg/ml), cefepime (200 mg/ml), pre-pen (undiluted), penicillin G (10,000 U/ml), ampicillin (20 mg/ml) and histamine (6 mg/ml). Concentrations for the first intradermal testing; cefazolin (3.3mg/ml), cefuroxime (1 mg/ml), ceftazidime (1 mg/ml), ceftriaxone (1 mg/ml), cefepime (2 mg/ml), Pre-PEN (undiluted), penicillin G (1000 U/ml), ampicillin (20 mg/ml), and histamine (0.1 mg/ml). Concentrations for the second intradermal testing; cefazolin (33mg/ml), cefuroxime (10 mg/ml), ceftazidime (10 mg/ml), ceftriaxone (10 mg/ml), cefepime (20 mg/ml), Pre-PEN (undiluted), penicillin G (10,000 U/ml), ampicillin (20 mg/ml) and histamine (0.1 mg/ml). Histamine and saline will be used as positive and negative controls.
Participants will undergo a 3-step double-blind placebo-controlled drug challenge to a cephalosporin antibiotic that shares a similar side chain with their culprit. This will be cefepime for those allergic to ceftriaxone, cefaclor for those allergic to cephalexin, cefixime for those allergic to cefdinir, cefdinir for those allergic to cefixime, cephalexin for those allergic to cefaclor or cephadroxil, and ceftriaxone for those allergic to cefepime, cefuroxime, or cefpodoxime. The challenges are 1:1 randomized to the order of active drug versus placebo. In Step 1, participants will receive 1:1000 of a full dose of either the culprit drug or placebo, followed by a 30-minute observation period. In Step 2, participants will receive 1:50 of a full dose of either, followed by another 30-minute observation period. In Step 3, participants are administered the full dose of either agent, followed by a 60-minute observation period. The same testing process is repeated for the second challenge.
Participants will undergo a 3-step double-blind placebo-controlled drug challenge to a cephalosporin antibiotic that has a dissimilar side chain to their culprit. This will be ceftriaxone for those allergic to cefazolin, and cefazolin for those allergic to any other cephalosporin. The challenges are 1:1 randomized to the order of active drug versus placebo. In Step 1, participants will receive 1:1000 of a full dose of either the culprit drug or placebo, followed by a 30-minute observation period. In Step 2, participants will receive 1:50 of a full dose of either, followed by another 30-minute observation period. In Step 3, participants are administered the full dose of either agent, followed by a 60-minute observation period. The same testing process is repeated for the second challenge.
Participants will optionally undergo a 3-step double-blind placebo-controlled drug challenge to Amoxicillin. The challenges are 1:1 randomized to the order of active drug versus placebo. In Step 1, participants will receive 1:1000 of a full dose of either the culprit drug or placebo, followed by a 30-minute observation period. In Step 2, participants will receive 1:50 of a full dose of either, followed by another 30-minute observation period. In Step 3, participants are administered the full dose of either agent, followed by a 60-minute observation period. The same testing process is repeated for the second challenge. The order of challenge to similar vs. dissimilar cephalosporin will be randomized as well.
After double-blind skin testing, participants will undergo a 3-step double-blind placebo-controlled drug challenge to their culprit cephalosporin (the cephalosporin they are suspected to be allergic to, either cefazolin, ceftazidime, ceftriaxone, cefepime, cephalexin, cefaclor, cefadroxil, cefuroxime, cefpodoxime, cefdinir, or cefixime). The challenges are 1:1 randomized to the order of active drug versus placebo. In Step 1, participants will receive 1:1000 of a full dose of either the culprit drug or placebo, followed by a 30-minute observation period. In Step 2, participants will receive 1:50 of a full dose of either, followed by another 30-minute observation period. In Step 3, participants are administered the full dose of either agent, followed by a 60-minute observation period. The same testing process is repeated for the second challenge.
Eligibility Criteria
You may qualify if:
- Age 18-70 years old.
- Reaction history consistent with a potential immediate hypersensitivity reaction (pruritus, urticaria, erythema, angioedema, bronchospasm, wheezing, shortness of breath, anaphylaxis, or hypotension) to cefazolin, ceftazidime, ceftriaxone, cefepime, cephalexin, cefaclor, cefadroxil, cefuroxime, cefpodoxime, cefdinir, or cefixime.
- English speaking or non-English speaking with translation services available.
You may not qualify if:
- Severe concomitant medical condition (e.g., unstable coronary artery disease, congestive heart failure, severe chronic obstructive pulmonary disease, poorly controlled asthma, chronic renal failure, cirrhosis, or end-stage liver disease.)
- History of Clostridioides difficile infection
- Chronic spontaneous urticaria or systemic mastocytosis
- Incident reaction required cardiopulmonary resuscitation
- Reaction to 2 or more cephalosporin antibiotics
- Active infection or antibiotic treatment within 7 days
- Treatment with systemic antihistamines or corticosteroids within 7 days
- Treatment with omalizumab or dupilumab within 60 days
- Significant immunosuppression
- Treatment with a beta-blocker or ACE inhibitor within 7 days
- Use of investigational drugs within 60 days of participation
- Anaphylaxis in the last 30 days
- Penicillin anaphylaxis within the past year confirmed with positive penicillin skin tests
- Prison or jail inmates, pregnant women, severe cognitive impairment
- Current, diagnosed, mental illness or current, diagnosed, or self-reported drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
Mayo Clinic Arizona
Scottsdale, Arizona, 14607, United States
University of California, San Francisco
San Francisco, California, 94143, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Rochester General Hospital
Rochester, New York, 14621, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Kimberly G Blumenthal, MD, MSc
Mayo Clinic
- PRINCIPAL INVESTIGATOR
David A Khan, MD
University of Texas Southwestern Medical Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Skin test reagents will be labeled blinded and prepared by a trained clinical trials pharmacy to maintain blinding. Drug challenges will be performed double-blind in a similar manner. The administrator, reader, and participant will all be blinded for each of these procedure types.
- Purpose
- DIAGNOSTIC
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
April 17, 2024
First Posted
May 9, 2024
Study Start
May 5, 2025
Primary Completion (Estimated)
July 1, 2028
Study Completion (Estimated)
December 31, 2028
Last Updated
March 19, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
- Time Frame
- All scientific data generated from this project will be made available as soon as possible, and no later than the time of publication or the end of the funding period, whichever comes first. The duration of preservation and sharing of the data will be a minimum of 5 years after the funding period.
- Access Criteria
- Access to the data will be shared under controlled-access conditions as required by the policies of NIH/NIAID and the Mass General Brigham (MGB), which will serve as the sIRB. In accordance with HIPAA, scientific data derived from humans will be protected through de-identification, removal of information that may be used to infer the identity and shared under controlled-access conditions as required by NIH/NIAID and MGB institutional policy.
Data will include demographics, clinical and procedure outcomes, and laboratory results. Investigators will preserve and share de-identified individual participant-level data (IPD) through submission to a controlled-access public repository. Investigators will apply the Safe Harbor method for de-identification of participant data. Participant informed consent forms will reflect this plan. To facilitate the use and interpretation of these data, the study protocol, data collection forms, case report forms, data dictionary, manual of operations, statistical analysis plan, and source code will be shared. Investigators will use Persistent Unique Identifiers (PIDs) to improve data findability across all dissemination outputs. PIDs used will include ORCID iDs for people, DOIs for outputs (e.g., datasets, protocols), and Research Resource IDentifiers (RRIDs) for resources. Investigators will also use indexed metadata to make scientific data easily findable.