Diagnostic Testing for Cephalosporin Allergy

(DACAT Trial)

Recruiting at 5 trial locations

Overseen By Ana D Fernandes, MA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: Antihistamines, Corticosteroids, Beta-blockers, ACE inhibitors

Disqualifiers: Severe medical conditions, Infection, Anaphylaxis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

300 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as systemic antihistamines, corticosteroids, beta-blockers, and ACE inhibitors, at least 7 days before participating. If you are on omalizumab or dupilumab, you need to stop them 60 days before the trial. Please consult with the trial team for specific guidance on your medications.

What data supports the effectiveness of the drug used in the Diagnostic Testing for Cephalosporin Allergy trial?

Research shows that many people who think they are allergic to beta-lactam antibiotics, like penicillins and cephalosporins, are not truly allergic. Testing can safely confirm or rule out these allergies, allowing more people to use these effective antibiotics without unnecessary avoidance. ^{1 2 3 4 5}

Is diagnostic testing for cephalosporin allergy safe?

Beta-lactam antibiotics, including cephalosporins, can cause allergic reactions, which are the most common drug allergies worldwide. While most reactions are mild, some can be severe, so it's important to diagnose allergies accurately. Aztreonam, a type of beta-lactam, shows low cross-reactivity with other beta-lactams and is generally well-tolerated, even by those allergic to penicillin. ^{1 6 7 8 9}

How is the drug for cephalosporin allergy testing different from other treatments?

This drug is unique because it focuses on diagnosing cephalosporin allergies by identifying specific allergenic structures recognized by IgE antibodies, which helps in developing targeted diagnostic tests. Unlike other treatments, it uses a combination of skin and oral provocation tests to confirm or exclude allergies, providing a more comprehensive approach to diagnosis. ^{1 7 10 11 12}

Research Team

David A Khan, MD

Principal Investigator

University of Texas Southwestern Medical Center

Kimberly G Blumenthal, MD, MSc

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for individuals who have had allergic reactions or anaphylaxis to cephalosporin antibiotics. Participants should not currently be on beta-lactam antibiotics and must have a history of immediate reaction to at least one cephalosporin.

Inclusion Criteria

I am between 18 and 70 years old.

Reaction history consistent with a potential immediate hypersensitivity reaction to specified cephalosporin antibiotics

I speak English or have access to a translator.

Exclusion Criteria

I do not have severe heart, lung, kidney, or liver conditions.

Prison or jail inmates, pregnant women, severe cognitive impairment

My vital signs were not normal or I was physically unstable during my first visit.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline and Initial Testing

Baseline screening, sample collection, double-blind skin testing to a beta-lactam panel, and a double-blind placebo-controlled challenge to their culprit cephalosporin antibiotic

1 week

1 visit (in-person)

Follow-up Testing for Allergic Participants

Double-blind placebo-controlled challenges to similar and dissimilar side chain cephalosporins to assess cross-reactivity, followed by a penicillin challenge

4 weeks

3 visits (in-person)

End-of-Study Visit

Venipuncture and blood collection for final assessments

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Beta-lactam antibiotic

Trial Overview The study tests the safety and effectiveness of various cephalosporins through skin testing and controlled drug challenges, aiming to improve diagnostic methods for those with suspected cephalosporin allergies.

Participant Groups

Group I: Similar cephalosporin first Experimental Treatment 5 Interventions

In 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.

Group II: Dissimilar cephalosporin first Experimental Treatment 5 Interventions

In 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.

Beta-lactam antibiotic is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Beta-lactam antibiotics for:

• Bacterial infections
• Pneumonia
• Urinary tract infections
• Skin and soft tissue infections

Approved in United States as Beta-lactam antibiotics for:

• Bacterial infections
• Pneumonia
• Urinary tract infections
• Skin and soft tissue infections
• Cystic fibrosis pulmonary exacerbations

Approved in Canada as Beta-lactam antibiotics for:

• Bacterial infections
• Pneumonia
• Urinary tract infections
• Skin and soft tissue infections

Approved in Japan as Beta-lactam antibiotics for:

• Bacterial infections
• Pneumonia
• Urinary tract infections
• Skin and soft tissue infections

Approved in China as Beta-lactam antibiotics for:

• Bacterial infections
• Pneumonia
• Urinary tract infections
• Skin and soft tissue infections

Approved in Switzerland as Beta-lactam antibiotics for:

• Bacterial infections
• Pneumonia
• Urinary tract infections
• Skin and soft tissue infections

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Findings from Research

Most reported penicillin allergies are not clinically significant, and skin testing can safely confirm or refute true IgE-mediated allergies, allowing for the safe use of penicillin in many patients.

There is minimal cross-reactivity between penicillins and other beta-lactam antibiotics, meaning that cephalosporins and other alternatives can be safely used even in patients with a confirmed penicillin allergy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Penicillin and beta-lactam allergy: epidemiology and diagnosis. Macy, E.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Structural determinants of antibiotic allergy. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Impact of an Inpatient Allergy Guideline on β-Lactam and Alternative Antibiotic Use. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Management of Beta-Lactam Antibiotics Allergy: A Real-Life Study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Penicillin and beta-lactam allergy: epidemiology and diagnosis. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical and genetic risk factors of self-reported penicillin allergy. [2015]

6. Argentina pubmed.ncbi.nlm.nih.gov

[Allergic Reactions to Betalactams in Pediatrics: Recommendations for diagnosis and treatment]. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Immediate hypersensitivity reactions to beta-lactam antibiotics. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Immunogenicity and cross-allergenicity of aztreonam. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Antibiotic Allergy in Children: More than Just a Label. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Educational case series: β-lactam allergy and cross-reactivity. [2011]

11. Singapore pubmed.ncbi.nlm.nih.gov

Assessment of a self-designed protocol on patients with adverse reactions to beta-lactam antibiotics. [2015]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Diagnosis of immediate hypersensitivity to β-lactam antibiotics can be made safely with current approaches. [2019]