Diagnostic Testing for Cephalosporin Allergy

(DACAT Trial)

Recruiting at 5 trial locations

Overseen By Cara Yelverton, BSc, PhD

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores better ways to diagnose cephalosporin allergies and improve future testing methods. Participants will help researchers understand how different cephalosporins, a type of antibiotic, with similar or dissimilar chemical structures affect those with known allergies. Individuals who have experienced immediate allergic reactions, such as hives, swelling, or difficulty breathing after taking certain cephalosporin antibiotics, may be a good fit. The study aims to develop safer guidelines for using these antibiotics in people with allergies.

As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to important advancements in allergy testing.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that cephalosporins are generally safe for people with penicillin allergies. Studies have found that allergic reactions mainly occur when the drugs have very similar chemical structures.

For cephalosporins with different structures, the risk of an allergic reaction is low, making them usually safe for those with a penicillin allergy.

For cephalosporins with similar structures, early reports showed some allergic reactions between penicillins and these cephalosporins. However, the risk is not as high as once thought, and many people with penicillin allergies can still safely use these cephalosporins.

Overall, research suggests that both types of cephalosporins are generally safe and well-tolerated, with a low risk of severe allergic reactions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it aims to improve the way we diagnose cephalosporin allergies, a common concern with antibiotic treatments. Unlike traditional methods that don't differentiate between similar and dissimilar side chain reactions, this approach uses a double-blind placebo-controlled challenge to better pinpoint specific allergies. By testing both similar and dissimilar side chain cephalosporins in a controlled setting, researchers hope to provide more precise and personalized information about a patient's allergy profile. This could lead to safer antibiotic use and fewer unnecessary restrictions on what antibiotics people can take.

What evidence suggests that this trial's treatments could be effective for cephalosporin allergy?

Research has shown that allergies to cephalosporin antibiotics often arise from their side-chain structure. One study found that 91% of these allergies relate to the side chain, suggesting that using a cephalosporin with a different side chain might be safer. In this trial, participants with confirmed cephalosporin allergies will undergo a double-blind, placebo-controlled drug challenge. In one arm, participants will first receive a cephalosporin with a dissimilar side chain, while in the other arm, they will first receive a cephalosporin with a similar side chain. These findings suggest that using cephalosporins with different side chains could be a promising option for people with cephalosporin allergies. ^{6 7 8 9 10}

Who Is on the Research Team?

David A Khan, MD

Principal Investigator

University of Texas Southwestern Medical Center

Kimberly G Blumenthal, MD, MSc

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06406114

Optimizing the Diagnostic Approach to Cephalosporin ... Among those with confirmed cephalosporin allergy, the skin test diagnostic characteristics with a dissimilar side-chain cephalosporin will be determined, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6955146/

Cephalosporin Allergy: Current Understanding and Future ... Fifty-one cases (40.1%) were confirmed as allergic with 76.4% positive by skin tests, 5.9% with negative skin tests and positive ...

3. jaci-global.org jaci-global.org/article/S2772-8293(24)00147-4/fulltext

Evaluation of cephalosporin allergy: Survey of drug ... We aimed to assess current cephalosporin allergy testing practices using real case examples. Methods An 18-question REDCap survey was sent to the 136 members.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7855229/

Testing Strategies and Predictors for Evaluating Immediate ... In terms of cephalosporin allergy, 88 reported cephalosporin allergy only, 240 of 780 (34%) reported allergy to both penicillins and cephalosporins, and 452 of ...

5. journalofinfection.com journalofinfection.com/article/S0163-4453(25)00089-1/fulltext

Development and validation of a cephalosporin allergy ... Like penicillin allergy labels, cephalosporin allergy labels go largely unverified and drive inappropriate antibiotic use.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6789778/

Cephalosporins: A Focus on Side Chains and β-Lactam Cross ... However, numerous data have suggested that even in confirmed penicillin allergic patients, cephalosporin use is safe due to the low cross- ...

7. unmc.edu unmc.edu/intmed/_documents/id/asp/clinicpath-beta-lactam-cross-reaction-tip-sheet.pdf

Beta-lactam Allergy Tip Sheet This table shows penicillins and cephalosporins with similar side chains. An X in a square indicates the two beta-lactams share a similar side chain structure.

8. adsp.nm.org adsp.nm.org/allergy-resources.html

Allergy Resources If the patient has a moderate risk allergy, check the cross-reactivity table, a structurally dissimilar side chain cephalosporin can be administered without ...

9. idmp.ucsf.edu idmp.ucsf.edu/content/allergy-beta-lactam

Allergy (Beta-lactam) | Infectious Diseases Management ... Empty boxes indicate that side chains are dissimilar and there is no/minimal risk for cross-reactivity. Cefazolin (1st) and ceftaroline (5th) have dissimilar ...

10. idstewardship.com idstewardship.com/cross-reactivity-cephalosporins-penicillins-story-side-chains/

Cross-Reactivity Between Cephalosporins and Penicillins Recent studies show significant cross-reactivity only occurs when cephalosporins and penicillins share nearly identical side chains—e.g., cephalexin with ...