Geisinger Antibiotic Allergy Pilot Program: Assess and Address

NCT05464615 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 2022-0191
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Penicillin Allergy

Outcome Measures

Primary Outcomes (1)

• Success Rate of the Graded Amoxicillin Challenge

  Investigators have created a simplified scoring system, the questionnaire, to identify low-risk patients that have a minimal risk of allergic reactions on exposure to penicillin or its derivative, so that patients with low risk will be offered a test dose (graded challenge) of amoxicillin to safely de-label penicillin allergy. If the questionnaire is designed appropriately for such a stratification process, no or at least minimal cases of post-challenge allergic reaction should be noted.

  The success rate will be determined at the completion within 1 year post implementation of the protocol.

Secondary Outcomes (2)

• Allergic reactions in low-risk patients

  Allergic reactions in low-risk patients Investigators will review and analyze the number and types of post-challenge allergic reaction in low risk patients within 1 year post implementation of the protocol

• Provider input on the GAAP Questionnaire to Identify Risk levels

  Surveys will be sent to participating providers 1-2 weeks post administration of the GAAP questionnaire.This process will be completed within 1 year post implementation of the protocol.

Study Arms (1)

Amoxicillin Graded Challenge

EXPERIMENTAL

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

Drug: Amoxicillin

Interventions

Amoxicillin DRUG

We will initially administer 1/5th (56 mg) of the goal dose of amoxicillin (256 mg) by oral route following the procedure outlined below. The total goal dose to be administered is amoxicillin 256 mg (3.2 ml of 400 mg/5 ml). These were numbers that came about for significance in relabeling penicillin allergies in patients in previous studies.

Amoxicillin Graded Challenge

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hospitalized male or female patients with a history of Penicillin (PCN) allergy or PCN-derivative allergy as reported by patient or documented in Epic
• ≥18 years of age
• Patients with a medical need for treatment with a PCN or PCN-derivative or other beta-lactam antibiotics as determined by an inpatient provider
• Able and willing to provide consent in English.

You may not qualify if:

• History of documented immediate-onset severe allergic reaction or delayed onset hypersensitivity reaction to a PCN or PCN-derivative
• Patients who are hemodynamically unstable (e.g., pulse oximetry O2 saturation \<90 %, respiratory rate \>=21 per minute, severe hypoxia requiring non-invasive ventilation, high-flow nasal canula, or mechanical ventilation, refractory hypotension requiring vasopressor support, heart rate \>100 beats per minute, etc.)
• Patients with uncontrolled pulmonary diseases (like exacerbation of asthma, Chronic Obstructive Pulmonary Disease (COPD), and/or other forms of chronic lung diseases)

Sponsors & Collaborators

• Geisinger Clinic: lead

Study Sites (3)

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

RECRUITING

Geisinger Community Medical Center

Scranton, Pennsylvania, 18510, United States

RECRUITING

Geisinger Wyoming Valley

Wilkes-Barre, Pennsylvania, 18711, United States

RECRUITING

Related Publications (14)

• Blumenthal KG, Phillips EJ. Positioning Drug Allergy Delabeling as a Critical Tool for Precision Medicine, Quality Improvement, and Public Health. J Allergy Clin Immunol Pract. 2020 Oct;8(9):2916-2919. doi: 10.1016/j.jaip.2020.07.046. Epub 2020 Aug 8. No abstract available.

  PMID: 32781047 BACKGROUND

• Louisias M, Wickner P. Drug allergy delabeling in the clinical setting: An all-hands-on-deck opportunity. Ann Allergy Asthma Immunol. 2020 Jun;124(6):542-543. doi: 10.1016/j.anai.2020.02.017. Epub 2020 Mar 6. No abstract available.

  PMID: 32147524 BACKGROUND

• Evaluation and Diagnosis of Penicillin Allergy for Healthcare Professionals | Community | Antibiotic Use | CDC. Published January 16, 2019. Accessed March 11, 2021. https://www.cdc.gov/antibiotic-use/community/for-hcp/Penicillin-Allergy.html

  BACKGROUND

• Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273. doi: 10.1016/j.anai.2010.08.002.

  PMID: 20934625 BACKGROUND

• Macy E, Contreras R. Health care use and serious infection prevalence associated with penicillin "allergy" in hospitalized patients: A cohort study. J Allergy Clin Immunol. 2014 Mar;133(3):790-6. doi: 10.1016/j.jaci.2013.09.021. Epub 2013 Nov 1.

  PMID: 24188976 BACKGROUND

• Blumenthal KG, Lu N, Zhang Y, Li Y, Walensky RP, Choi HK. Risk of meticillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study. BMJ. 2018 Jun 27;361:k2400. doi: 10.1136/bmj.k2400.

  PMID: 29950489 BACKGROUND

• Parikh P, Patel NC, Trogen B, Feldman E, Meadows JA. The economic implications of penicillin allergy. Ann Allergy Asthma Immunol. 2020 Dec;125(6):626-627. doi: 10.1016/j.anai.2020.08.003. Epub 2020 Aug 6. No abstract available.

  PMID: 32768634 BACKGROUND

• Livirya S, Pithie A, Chua I, Hamilton N, Doogue M, Isenman H. Oral amoxicillin challenge for low-risk penicillin allergic patients. Intern Med J. 2022 Feb;52(2):295-300. doi: 10.1111/imj.14978. Epub 2022 Jan 12.

  PMID: 32672891 BACKGROUND

• Krishna MT, Misbah SA. Is direct oral amoxicillin challenge a viable approach for 'low-risk' patients labelled with penicillin allergy? J Antimicrob Chemother. 2019 Sep 1;74(9):2475-2479. doi: 10.1093/jac/dkz229.

  PMID: 31167024 BACKGROUND

• Trubiano JA, Vogrin S, Chua KYL, Bourke J, Yun J, Douglas A, Stone CA, Yu R, Groenendijk L, Holmes NE, Phillips EJ. Development and Validation of a Penicillin Allergy Clinical Decision Rule. JAMA Intern Med. 2020 May 1;180(5):745-752. doi: 10.1001/jamainternmed.2020.0403.

  PMID: 32176248 BACKGROUND

• Artino AR Jr, La Rochelle JS, Dezee KJ, Gehlbach H. Developing questionnaires for educational research: AMEE Guide No. 87. Med Teach. 2014 Jun;36(6):463-74. doi: 10.3109/0142159X.2014.889814. Epub 2014 Mar 24.

  PMID: 24661014 BACKGROUND

• Brown TM. Design and interpretation of non-inferiority studies: A clinician's perspective. J Nucl Cardiol. 2017 Dec;24(6):1994-1997. doi: 10.1007/s12350-017-1034-5. Epub 2017 Aug 10. No abstract available.

  PMID: 28799025 BACKGROUND

• Schumi J, Wittes JT. Through the looking glass: understanding non-inferiority. Trials. 2011 May 3;12:106. doi: 10.1186/1745-6215-12-106.

  PMID: 21539749 BACKGROUND

• Antibiotic Prescribing and Use. CDC. 2017 Oct; https://www.cdc.gov/antibiotic-use/clinicians/penicillin-allergy.html

  BACKGROUND

MeSH Terms

Interventions

Amoxicillin

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Taesung Kwon, MD

  Geisinger Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karla Frank

CONTACT

570-214-4215; kfrank6@geisinger.edu

Taesung Kwon, MD

CONTACT

tkwon@geisinger.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: The participants and investigators will know when the dosing of penicillin being administered and increased/decreased.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician Infectious Disease

Model Details: Prospective non-inferiority study

Study Record Dates

• First Submitted: July 12, 2022
• First Posted: July 19, 2022
• Study Start: March 4, 2024
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: August 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)