Amoxicillin for Penicillin Allergy

(GAAP Trial)

Recruiting at 2 trial locations

Overseen By Karla Frank

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Geisinger Clinic

Must be taking: Penicillin, Penicillin-derivatives

Disqualifiers: Severe allergic reaction, Unstable hemodynamics, Uncontrolled pulmonary diseases

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assist individuals who believe they are allergic to penicillin by testing if they can safely take amoxicillin, a penicillin-based antibiotic. Research has suggested that many of these individuals might not actually be allergic, potentially allowing them to use penicillin-based treatments when necessary. Participants who have been diagnosed with a penicillin allergy, are hospitalized, and require this type of antibiotic might be suitable candidates. The trial involves administering a small, supervised dose of amoxicillin to assess safety. If successful, participants could have the penicillin allergy label removed from their medical records. As an Early Phase 1 trial, this research focuses on understanding how amoxicillin affects individuals who believe they are allergic, offering a chance to safely explore treatment options.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your healthcare provider.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that amoxicillin, like other penicillin antibiotics, can cause serious allergic reactions. These reactions, known as anaphylaxis, can be life-threatening and require immediate medical attention. Although rare, such severe reactions can occur. Therefore, individuals allergic to penicillin or similar antibiotics should avoid amoxicillin.

For those without allergies, amoxicillin is usually well-tolerated. Common side effects are mild, such as an upset stomach or a rash. During the trial, participants will begin with a small dose under supervision. This approach ensures safety by monitoring for any immediate allergic reactions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard approach for penicillin allergies, which often involves avoiding penicillin-based antibiotics altogether, this protocol uses an amoxicillin graded challenge to potentially verify whether individuals truly have an allergy. Researchers are excited because it directly tests the body's response to amoxicillin in a controlled, step-by-step manner, which might reveal that some people labeled as allergic can actually tolerate the drug safely. This could open up more treatment options for patients who need penicillin-type antibiotics, which are often highly effective and cost-efficient.

What evidence suggests that this trial's treatment could be effective for penicillin allergy?

Research has shown that most people who believe they are allergic to penicillin can safely take amoxicillin. In one study, only 0.5% of patients had an allergic reaction when tested with penicillin. Another study found that 85% of people who thought they were allergic to penicillin experienced only mild skin reactions, which are less likely to recur. Tests in children also demonstrated that most could take penicillin without issues after their allergy label was removed. These findings suggest that many people who think they are allergic might not be, and amoxicillin could be safe for them. Participants in this trial will undergo an Amoxicillin Graded Challenge to assess their tolerance to the medication. ^{6 7 8 9 10}

Who Is on the Research Team?

Taesung Kwon, MD

Principal Investigator

Geisinger Clinic

Are You a Good Fit for This Trial?

This trial is for hospitalized adults who have a history of penicillin allergy noted in their medical records or reported by themselves. They must need treatment with penicillin or similar antibiotics and be able to consent in English.

Inclusion Criteria

Hospitalized male or female patients with a history of Penicillin (PCN) allergy or PCN-derivative allergy as reported by patient or documented in Epic

I need treatment with a specific type of antibiotic as determined by my doctor.

I can and agree to consent in English.

Exclusion Criteria

History of documented immediate-onset severe allergic reaction or delayed onset hypersensitivity reaction to a PCN or PCN-derivative

I do not have uncontrolled lung problems like severe asthma or COPD.

I am not experiencing severe breathing or heart issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Low-risk patients undergo a graded amoxicillin challenge to assess penicillin allergy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for allergic reactions and effectiveness of de-labeling

1 year

Periodic reviews

What Are the Treatments Tested in This Trial?

Interventions

• Amoxicillin

Trial Overview The study tests if patients with low-risk scores from a questionnaire can safely take amoxicillin, a penicillin derivative. Those who pass the test dose without an allergic reaction may have their penicillin allergy label removed.

How Is the Trial Designed?

Group I: Amoxicillin Graded Challenge Experimental Treatment 1 Intervention

1. Obtain baseline vitals (heart rate, O2 saturation, blood pressure and respiratory rate). 2. Administer 0.7 ml (56 mg) of amoxicillin 400 mg/ 5ml orally followed by 30 minutes of observation for allergy symptoms and other adverse reactions (e.g., itching, hives, swelling, coughing, wheezing, throat tightness, difficulty breathing, abdominal pain, vomiting, lightheadedness, hypotension, low oxygen saturation, tachycardia) 3. If no allergy or adverse symptoms are noted, administer 2.5 ml (200 mg) of amoxicillin followed by 90 minutes of observation

Amoxicillin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Amoxicillin for:

• Bacterial infections
• Respiratory tract infections
• Urinary tract infections
• Skin and soft tissue infections
• Ear, nose and throat infections

Approved in United States as Amoxicillin for:

• Infections of the ear, nose, throat, genitourinary tract, skin and skin structure, and lower respiratory tract

Approved in Canada as Amoxicillin for:

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

Who Is Running the Clinical Trial?

Geisinger Clinic

Lead Sponsor

Trials

159

Recruited

1,976,000+

Published Research Related to This Trial

A study reviewing 325 patient charts found that adjusting electronic medical record alerting rules for β-lactam antibiotics resulted in no cases of anaphylaxis (0%) among patients who received these medications after being documented as allergic to penicillins.

The new alerting rules, which only flagged similar side chain antibiotics, effectively reduced unnecessary alerts for prescribers while maintaining patient safety, although some patients did experience non-anaphylactic delayed reactions like rashes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

β-lactam exposure outcome among patients with a documented allergy to penicillins post-implementation of a new electronic medical record system and alerting rules. Buffone, B., Lin, YC., Grant, J.[2022]

In a study of 30 penicillin-allergic subjects in Italy, ampicillin (AMP) was identified as the most common drug causing allergic reactions, with 15 patients experiencing severe anaphylactic responses.

Skin tests revealed that 76.6% of patients reacted positively to a mixture of minor determinants, indicating a heterogeneous IgE response, but there was little specific reactivity to AMP itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immediate hypersensitivity to penicillins. Studies on Italian subjects. Romano, A., Blanca, M., Mayorga, C., et al.[2019]

The commonly believed 10% cross-allergy risk between penicillin and cephalosporins is incorrect; not all cephalosporins pose the same risk.

Certain cephalosporins like cephalothin, cephalexin, cefadroxil, and cefazolin do increase the risk of allergic reactions in patients with penicillin allergies, while others like cefprozil, cefuroxime, cefpodoxime, ceftazidime, and ceftriaxone do not.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cephalosporins can be prescribed safely for penicillin-allergic patients. Pichichero, ME.[2008]

A significant majority (80% to 90%) of individuals who self-report a penicillin allergy can actually tolerate penicillins after proper evaluation, suggesting that many may be misclassified as allergic.

Mislabeling patients as penicillin-allergic can lead to unnecessary use of broader-spectrum antibiotics, which increases the risk of antibiotic resistance and higher healthcare costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation and Management of Penicillin Allergy. Pongdee, T., Li, JT.[2019]

Penicillin, particularly amoxicillin, is a common cause of allergic reactions and anaphylaxis, with adverse events occurring in 1% to 10% of cases, and up to 10% of these can be life-threatening, especially in patients without prior allergy history.

The case of a 5-year-old girl who experienced a severe allergic reaction to amoxicillin highlights the importance of recognizing and managing penicillin hypersensitivity, especially in pediatric dental settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reaction to amoxicillin: a case report. da Fonseca, MA.[2013]

Many patients labeled with a penicillin allergy do not actually have a confirmed allergy, which can lead to unnecessary avoidance of penicillins and other related antibiotics.

Understanding the characteristics that differentiate low-risk from high-risk patients for true penicillin allergy is crucial for proper assessment and management of antibiotic treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Penicillin allergy-getting the label right. [2017]

In a study of 129 patients with documented IgE-mediated penicillin allergy, the in vitro tests for specific IgE to amoxicilloyl (AXO) and benzylpenicilloyl (BPO) showed that combining these tests improves diagnostic accuracy, especially for patients with immediate allergic reactions to amoxicillin.

The results indicated that 74% of patients with positive skin tests had at least one positive in vitro test, highlighting the importance of using both in vivo and in vitro methods to accurately diagnose penicillin allergies, particularly in cases where skin tests may be negative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of Pharmacia CAP System RAST FEIA amoxicilloyl and benzylpenicilloyl in patients with penicillin allergy. Blanca, M., Mayorga, C., Torres, MJ., et al.[2019]

In a study of 1057 ambulatory patients, 9.4% reported a penicillin allergy, with Penicillin A being the most commonly cited antibiotic, indicating that this belief is prevalent even outside hospital settings.

The study highlights the need for careful patient questioning to potentially correct false diagnoses of penicillin allergy, as many patients may be unnecessarily avoiding an effective and affordable treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Frequency of self-reported penicillin allergy in the area of Seine-Saint-Denis (France)]. Branellec, A., Thomas, M., Fain, O., et al.[2016]

In a study of 224 patients labeled with 'penicillin allergy', 50% were successfully de-labeled, demonstrating that many patients may not actually be allergic to penicillin, especially when assessed carefully.

Administering an oral amoxicillin challenge without prior skin testing was found to be safe and effective for low-risk patients, allowing for better antibiotic therapy and improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral amoxicillin challenge for low-risk penicillin allergic patients. Livirya, S., Pithie, A., Chua, I., et al.[2022]

A case study of a woman who developed allergic reactions to amoxicillin-clavulanic acid after previously tolerating it well suggests that sensitization can occur even after prior exposure without issues.

Testing revealed that while she had undetectable IgE levels to several beta-lactam antibiotics, she developed specific IgE to penicillin V later, indicating a unique sensitization to the combination of amoxicillin and clavulanic acid rather than cross-reactivity with other beta-lactams.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective sensitization to clavulanic acid and penicillin V. González de Olano, D., Losada, PA., Caballer, Bde L., et al.[2013]

The PEN-FAST clinical decision rule effectively identifies low-risk penicillin allergies in a high-risk population, with a strong discrimination ability (AUC of 0.86) based on a study of 142 patients, most of whom reported anaphylaxis.

Using a cutoff of less than 3 points on the PEN-FAST score, only 6.9% of patients classified as low risk tested positive for an allergy, demonstrating a high negative predictive value (0.93) for safely delabeling amoxicillin allergy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive factors of amoxicillin immediate hypersensitivity and validation of PEN-FAST clinical decision rule. Piotin, A., Godet, J., Trubiano, JA., et al.[2022]

Citations

1. academic.oup.com academic.oup.com/jac/article/78/4/913/7069899

Health outcomes of penicillin allergy testing in children The most commonly reported outcomes were delabelling, subsequent penicillin courses, and tolerability to penicillin courses.

2. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/2806976

Efficacy of a Clinical Decision Rule to Enable Direct Oral ... The primary outcome of a positive oral penicillin challenge consistent with an immune-mediated reaction occurred in 1 of 187 patients (0.5%) in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10789979/

Oral amoxicillin challenges for low-risk penicillin-allergic ... We retrospectively reviewed the records of 136 veterans with a penicillin allergy label during a quality improvement initiative.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12048795/

Direct Amoxicillin Challenges for Penicillin Allergy Through ... Fifty-two (85%) reported a cutaneous-only index reaction to a penicillin, and 18 (30%) reported a reaction within 1 hour of penicillin dose at ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0163445324003025

Characteristics, risk factors and clinical impact of penicillin ... The main outcomes include the annual prevalence and incidence of penicillin and other antibiotic allergy labels. Multinominal logistic regression was used ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/050813s008lbl.pdf

moxatag - accessdata.fda.gov Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. • Serious anaphylactic reactions ...

7. drugs.com drugs.com/amoxicillin.html

Amoxicillin: Uses, Dosage, Side Effects, Warnings You should not use amoxicillin if you are allergic to any penicillin antibiotic, such as ampicillin, dicloxacillin, oxacillin, penicillin, or ...

8. rxlist.com rxlist.com/moxatag-drug.htm

Moxatag (Amoxicillin Extended-Release Tablets) Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. Although anaphylaxis is more ...

9. mayoclinic.org mayoclinic.org/drugs-supplements/amoxicillin-oral-route/description/drg-20075356

Amoxicillin (oral route) - Side effects & dosage This medicine may cause a serious allergic reaction called anaphylaxis, which can be life-threatening and require immediate medical attention.

10. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK482250/

Amoxicillin - StatPearls - NCBI Bookshelf - NIH Adverse Effects​​ Additional adverse drug reactions associated with amoxicillin are listed below. Chloramphenicol, macrolides, sulfonamides, and ...