Amoxicillin for Penicillin Allergy

(GAAP Trial)

Recruiting at 2 trial locations

Overseen By Nicole Lee

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Geisinger Clinic

Must be taking: Penicillin, Penicillin-derivatives

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

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a prospective non-inferiority study to evaluate penicillin allergy history in patients with reported penicillin allergy, who require penicillin or penicillin-derivative antibiotic during inpatient admission using a focused questionnaire. A simplified scoring system will be assigned to patient responses, and the total score will be utilized to identify low-risk patients that have a minimal risk of allergic reactions on exposure to penicillin or its derivative. Patients determined to have low risk based on this questionnaire will be offered a test dose (graded challenge) of amoxicillin in a supervised setting, and if they tolerate it, penicillin allergy label will be removed from patient's chart. We hypothesize that at least 95% of low-risk patients will successfully pass the graded amoxicillin challenge so the penicillin allergy label can be removed from their charts. A proportion as low as 0.85 would be a good clinical outcome and considered non-inferior to the expected proportion of 0.95.

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.

What data supports the effectiveness of the drug Amoxicillin for people with a penicillin allergy?

The research suggests that many people who believe they are allergic to penicillin may not actually be allergic, as shown by studies where patients tolerated amoxicillin without allergic reactions. This indicates that amoxicillin can be safely used in some individuals who are labeled as penicillin-allergic, potentially making it an effective treatment option for them. ^{1 2 3 4 5}

Is amoxicillin safe for people with a penicillin allergy?

Amoxicillin can cause allergic reactions in some people, especially those with a penicillin allergy. However, many people labeled as penicillin-allergic are at low risk of a true allergic reaction, and testing can help determine their actual risk. ^{4 6 7 8 9}

How is the drug Amoxicillin unique for treating penicillin allergy?

Amoxicillin is unique because it can be tolerated by many people who believe they are allergic to penicillin, potentially avoiding the need for broader-spectrum antibiotics that can lead to antibiotic resistance and higher healthcare costs. ^{1 2 3 10 11}

Research Team

Taesung Kwon, MD

Principal Investigator

Geisinger Clinic

Eligibility Criteria

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

I am 18 years old or older.

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.

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.

Trial Timeline

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

Treatment Details

Interventions

• Amoxicillin (Beta-lactam Antibiotic)

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.

Participant Groups

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 Canada for the following indications:

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

[Frequency of self-reported penicillin allergy in the area of Seine-Saint-Denis (France)]. [2016]

2. Denmark pubmed.ncbi.nlm.nih.gov

Immediate hypersensitivity to penicillins. Studies on Italian subjects. [2019]

3. Spain pubmed.ncbi.nlm.nih.gov

Selective sensitization to clavulanic acid and penicillin V. [2013]

4. Canada 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. [2022]

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

Predictive factors of amoxicillin immediate hypersensitivity and validation of PEN-FAST clinical decision rule. [2022]

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

Adverse reaction to amoxicillin: a case report. [2013]

7. Australia pubmed.ncbi.nlm.nih.gov

Oral amoxicillin challenge for low-risk penicillin allergic patients. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Penicillin allergy-getting the label right. [2017]

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

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

10. Denmark pubmed.ncbi.nlm.nih.gov

Clinical evaluation of Pharmacia CAP System RAST FEIA amoxicilloyl and benzylpenicilloyl in patients with penicillin allergy. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Evaluation and Management of Penicillin Allergy. [2019]