Clinical trial NCT04408508: Safety and Efficacy of an Oral Penicillin Challenge in Low Risk Hospitalized Patients
Official title: Safety and Efficacy of an Oral Penicillin Challenge in Low Risk Hospitalized Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Penicillin Allergy
Keywords: beta-lactam
penicillin
hypersensitivity
drug allergy
Lead sponsor: Saskatchewan Health Authority - Regina Area
Sponsor class: OTHER
First posted: 2020-05-29
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients reporting penicillin allergy will be enrolled based on eligibility criteria for direct oral amoxicillin challenge. There will be one treatment group of patients assigned low risk for penicillin allergy.
Primary purpose: OTHER

Brief summary: Penicillin allergy is the most common drug allergy reported by patients. Approximately 10% of the population and 20% of inpatients carry a label of penicillin allergy. However, less than 5%-10% of them have a confirmed allergy following comprehensive investigations. Reported penicillin allergy leads to higher medical costs and excess complications and presents a major challenge to antimicrobial stewardship.

There is a high demand for allergy services however penicillin allergy testing (including skin testing and oral drug challenge) is not routinely available for inpatients even in major centres. Direct oral amoxicillin challenges are safe and effective in delabeling low risk patients who report penicillin allergy in large paediatric and adult studies and does not necessitate specialist referral.

The study team seeks to determine the safety and efficacy of a single-dose oral penicillin challenge pilot program in adult in-patients with self-reported penicillin allergy admitted to hospital under the internal medicine Clinical Teaching Unit (CTU). The study investigators will determine the number of patients successfully delabelled of their "penicillin allergy" prior to discharge from hospital over a 12 month period. The study doctors will also assess the economic impact of the investigator's model and ease of implementation in the busy inpatient setting. In the future this model could be implemented generally as an inpatient or outpatient penicillin allergy program where low risk patients, who do not require referral to an allergist, are expeditiously delabelled.

Detailed description: Penicillin allergy is the most common drug allergy reported by patients. Approximately 10% of the population and 20% of inpatients carry a label of penicillin allergy. However, only \<5%-10% of them have a confirmed allergy following comprehensive investigations. Reported penicillin allergy leads to higher medical costs and excess complications and presents a major challenge to antimicrobial stewardship. There is a high demand for allergy services however penicillin allergy testing (including skin testing and oral drug challenge) is not routinely available for inpatients even in major centres. Consequently, patients with a penicillin allergy label receive alternative antibiotics such as carbapenems, fluoroquinolones, and vancomycin for the treatment of common and serious infections and for pre-surgical prophylaxis. Patients with penicillin allergy label have longer hospital stays and higher rates of infections with Clostridioides (Clostridium) difficile, VRE and MRSA in comparison with patients without a documented allergy.

Direct oral amoxicillin challenges are safe and effective in delabeling patients stratified as low risk for penicillin allergy in large pediatric and adult studies. Low-risk penicillin allergy histories include patients who have had isolated nonallergic symptoms (eg, gastrointestinal symptoms) or patients solely with a family history of a penicillin allergy, pruritus without rash, or remote (\>10 years) unknown reactions without features suggestive of an IgE-mediated reaction.

The study investigators seek to determine the safety and efficacy of a single-dose oral penicillin challenge pilot program in adult in-patients with self-reported penicillin allergy admitted to hospital under the internal medicine Clinical Teaching Unit (CTU). Identified patients that fulfill the exclusion and inclusion criteria will be reviewed at the time of discharge for suitability, as per the algorithm, modelled after a previous study of similar design. Based on patient's reported allergy, and upon obtaining informed consent, participants will receive a supervised challenge of amoxicillin 250 mg once orally and subsequently observed for 1 hour before discharge home. After antibiotic challenge, patient outcome will be defined as (1) tolerated oral challenge with no adverse drug reaction or (2) adverse drug reaction.

By challenging carefully selected low risk patient that are unlikely to be truly allergic while in hospital, the study doctors can delabel patients of their "penicillin allergy" and as a result cut health care expenditures and promote good antimicrobial stewardship. In the future this model could be implemented generally as an inpatient or outpatient penicillin allergy program where low risk patients, who do not require referral to an allergist, are expeditiously delabeled.

Eligibility criteria: Inclusion Criteria:

1. Assessed to be low risk of having a penicillin allergy as per the risk stratification questionnaire
2. One of the following: i) An unknown reaction \>10 years before, ii) A type A adverse drug reaction (pharmacologically predictable drug side effect or intolerance), or iii) A history of a benign childhood rash, nonurticarial rash, or maculopapular exanthem more than 10 years ago
3. Age 18 years or older
4. Hemodynamically stable and suitable for discharge home

Exclusion Criteria:

1. Declines participation in the study
2. Cognitive impairment and where a collateral history could not be obtained
3. History of anaphylaxis or angioedema attributed to a penicillin-based antibiotic
4. History of severe cutaneous adverse reactions attributed to a penicillin-based antibiotic
5. History of acute kidney injury or severe liver impairment attributed to a penicillin-based antibiotic
6. Currently taking an angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker or a beta blocker
7. Hemodynamically unstable
8. History of idiopathic urticaria or idiopathic anaphylaxis
9. Currently taking an antibiotic(s) for treatment of an active infection

Primary outcomes:
measure: Number of patients tolerating oral amoxicillin challenge
timeFrame: 12 months
Secondary outcomes:
measure: Number of patients reporting a delayed reaction to amoxicillin
timeFrame: 12 months
measure: Average delay in discharge attributable to amoxicillin challenge
timeFrame: 12 months
measure: The number of patients excluded from the study due to staff time constraints
timeFrame: 12 months
measure: Type of immediate reaction attributed to the oral amoxicillin: maculopapular rash, urticaria, angioedema, airway compromise, diarrhea, vomiting or other (including subjective symptoms)
timeFrame: 12 months
Other outcomes:
Locations:
Study officials:
affiliation: Saskatchewan Health Authority - Regina Area
name: Andrea Fong, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
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