Inpatient Penicillin Allergy Delabeling Study

NCT05020327 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: STUDY20200136
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The study will identify pediatric patients 3-18 years old who have penicillin allergy label in the electronic medical record. Those who are identified will be stratified into no-risk, low-risk and high-risk category using a screening questionnaire. The following definitions will be followed: No-risk: Patients who are historically labeled with penicillin allergy in the EMR based on family history alone OR those who have tolerated penicillin after a concerning incident without any reaction OR with penicillin allergy label but deny any history of reaction to any form of penicillin on screening questionnaire Low-risk: Patients with previous reaction not suggestive of anaphylaxis (defined below) AND not requiring hospitalization for the reaction OR reaction considered non- immunologic (e.g. diarrhea, nausea, yeast vaginitis) OR exposure to penicillin- containing antibiotic after the date of reported reaction with no anaphylaxis and hospitalization AND no serious types of delayed reactions such as Steven- Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute interstitial nephritis (AIN), drug-induced hepatitis or other documented organ injury, drug rash eosinophilia systemic symptoms (DRESS), hemolytic anemia, drug-induced cytopenia, and serum sickness. Patients who had delayed reaction (onset more than 24 hours) of isolated, non-progressive symptoms (such as rash/hives alone) also belong to this group. High-risk: Patients with penicillin allergy label on EMR with previous reaction suggestive of anaphylaxis (defined below) OR requiring hospitalization/epinephrine administration for the reaction OR reactions considered immunologic (angioedema, joint pains) OR involving serious types of reactions such as Steven-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute interstitial nephritis (AIN), drug-induced hepatitis or other documented organ injury, drug rash eosinophilia systemic symptoms (DRESS), hemolytic anemia, drug-induced cytopenia, and serum sickness. Patients who were previously diagnosed with penicillin allergy by an allergist also belong to the high-risk group. Patients in the no-risk group will be immediately delabeled. Patients in the high-risk group will be referred to allergy/immunology for further work up. The focus of this study is to identify the patients who belong to the low-risk group. This group of patients will be subjected to graded oral amoxicillin challenge testing. Those who will have reactions compatible with allergy will have their allergy status retained in the electronic medical record. Those that will not have reactions or those that will have reactions that are not compatible with allergy will be delabeled in the electronic medical record.

Conditions

Penicillin Allergy; Penicillin Sensitivity; Penicillin Reaction; Penicillin Intolerance

Keywords

Penicillin allergy; Penicillin delabeling

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Confirmed Allergy Status

  Participants with penicillin allergy status verification based on questionnaire and challenge

  3 hours

Secondary Outcomes (3)

• Number of Participants With no Penicillin Allergy Confirmed and De-labelled of Penicillin Allergy Based on Results of Questionnaire.

  3 hours

• Number of Participants Categorized as Low Risk for Penicillin Allergy Reaction With Confirmed True Penicillin Allergy as Measured by Failed Oral Amoxicillin Challenge

  3 hours

• Number of Participants With Confirmed True Allergy Without Challenge

  3 hours

Study Arms (3)

Low Risk Patients

EXPERIMENTAL

This is the group of patients who will undergo the graded oral amoxicillin challenge testing. Total dose of the amoxicillin will be 45 mg/kg (maximum of 1000 mg). 10 % of this dose will be given first followed by 90 % of the dose 30 minutes after. Each dose will be given only once.

Drug: Graded Oral Amoxicillin Challenge; Other: De-labelling in electronic medical record; Other: Referral to Allergy Immunology/Retention of Allergy Label

No Risk Patients

OTHER

Patients in the group will be de-labeled in the electronic medical record for No Risk for allergic reaction to amoxicillin based on screening questionnaire.

Other: De-labelling in electronic medical record

High Risk

OTHER

Patients in this group are deemed high risk for allergic reaction to penicillin based on screening questionnaire and will remain labeled with allergy in the electronic medical record. They will be referred as outpatient to allergy-immunology for further evaluation.

Other: Referral to Allergy Immunology/Retention of Allergy Label

Interventions

Graded Oral Amoxicillin Challenge DRUG

Oral amoxicillin at 45 mg/kg (maximum of 1000 mg) to be divided into two doses: 10 % initial dose and then 90% remaining dose - doses will be separated by 30 minute interval

Also known as: Amoxicillin Challenge

Low Risk Patients

De-labelling in electronic medical record OTHER

Patients with No Risk for allergic reaction will be de-labelled for allergy in the electronic medical record.

Low Risk Patients; No Risk Patients

Referral to Allergy Immunology/Retention of Allergy Label OTHER

Patients deemed to be High Risk for allergic reaction will be referred to Allergy Immunology as outpatient and allergy label will be retained.

High Risk; Low Risk Patients

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients 3-18 years old admitted at our institution with penicillin allergy label in electronic medical record
• Patients with available parent/s or legal guardian who can give both written and verbal consent to the oral challenge testing
• Patients with available parent/s or legal guardian during the conduct of oral amoxicillin challenge testing
• \- Patients who will be identified as low-risk patients based on the standardized screening questionnaire. Low-risk group patients are those patients with previous reaction not suggestive of anaphylaxis AND not requiring hospitalization for the reaction OR reaction considered non-immunologic (e.g. diarrhea, nausea, yeast vaginitis) OR exposure to penicillin-containing antibiotic after the date of reported reaction with no anaphylaxis and hospitalization AND no serious types of delayed reactions such as Steven-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute interstitial nephritis (AIN), drug-induced hepatitis or other documented organ injury, drug rash eosinophilia systemic symptoms (DRESS), hemolytic anemia, drug-induced cytopenia, and serum sickness. - ---- Patients who had delayed reaction (onset more than 24 hours) of isolated, non-progressive symptoms (such as rash/hives alone) also belong to this group.

You may not qualify if:

• Patients who cannot tolerate amoxicillin/penicillin by enteral route.
• Patients with no parents or legal guardian available to give both written and verbal consent to the oral challenge testing
• Patients with no available parents or legal guardian during the conduct of oral amoxicillin challenge testing
• Patients currently on antihistamine or have received antihistamine in the previous 48 hours
• Patients who are critically ill
• Patients who have been vomiting more than twice in the past 24 hours or are actively vomiting
• Patients with respiratory symptoms warranting oxygen therapy or pulmonary finding of wheezing or stridor
• Patients identified as having anaphylactic reaction to penicillin in the electronic medical record
• Patients who will be identified as no-risk patients based on the standardized screening questionnaire. No-risk group patients are those patients who are historically labeled with penicillin allergy in the EMR based on family history alone OR those who have tolerated penicillin after a concerning incident without any reaction OR with penicillin allergy label but deny any history of reaction to any form of penicillin on screening questionnaire
• Patients who will be identified as high-risk patients based on the standardized screening questionnaire. High-risk group patients are those patients with penicillin allergy label on EMR with previous reaction suggestive of anaphylaxis OR requiring hospitalization/epinephrine administration for the reaction OR reactions considered immunologic (angioedema, joint pains) OR involving serious types of reactions such as Steven-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute interstitial nephritis (AIN), drug-induced hepatitis or other documented organ injury, drug rash eosinophilia systemic symptoms (DRESS), hemolytic anemia, drug-induced cytopenia, and serum sickness. Patients who were previously diagnosed with penicillin allergy by an allergist also belong to the high-risk group.

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead

Study Sites (1)

University Hospitals Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Related Publications (16)

• Vyles D, Adams J, Chiu A, Simpson P, Nimmer M, Brousseau DC. Allergy Testing in Children With Low-Risk Penicillin Allergy Symptoms. Pediatrics. 2017 Aug;140(2):e20170471. doi: 10.1542/peds.2017-0471. Epub 2017 Jul 3.

  PMID: 28674112 RESULT

• du Plessis T, Walls G, Jordan A, Holland DJ. Implementation of a pharmacist-led penicillin allergy de-labelling service in a public hospital. J Antimicrob Chemother. 2019 May 1;74(5):1438-1446. doi: 10.1093/jac/dky575.

  PMID: 30753497 RESULT

• Blumenthal KG, Ryan EE, Li Y, Lee H, Kuhlen JL, Shenoy ES. The Impact of a Reported Penicillin Allergy on Surgical Site Infection Risk. Clin Infect Dis. 2018 Jan 18;66(3):329-336. doi: 10.1093/cid/cix794.

  PMID: 29361015 RESULT

• Au LYC, Siu AM, Yamamoto LG. Cost and Risk Analysis of Lifelong Penicillin Allergy. Clin Pediatr (Phila). 2019 Oct;58(11-12):1309-1314. doi: 10.1177/0009922819853014. Epub 2019 Jun 19.

  PMID: 31216862 RESULT

• Sagar PS, Katelaris CH. Utility of penicillin allergy testing in patients presenting with a history of penicillin allergy. Asia Pac Allergy. 2013 Apr;3(2):115-9. doi: 10.5415/apallergy.2013.3.2.115. Epub 2013 Apr 26.

  PMID: 23667835 RESULT

• Arnold A, Sommerfield A, Ramgolam A, Rueter K, Muthusamy S, Noble V, von Ungern-Sternberg BS, Lucas M. The role of skin testing and extended antibiotic courses in assessment of children with penicillin allergy: An Australian experience. J Paediatr Child Health. 2019 Apr;55(4):428-432. doi: 10.1111/jpc.14220. Epub 2018 Sep 13.

  PMID: 30209846 RESULT

• Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and Management of Penicillin Allergy: A Review. JAMA. 2019 Jan 15;321(2):188-199. doi: 10.1001/jama.2018.19283.

  PMID: 30644987 RESULT

• Kuruvilla M, Shih J, Patel K, Scanlon N. Direct oral amoxicillin challenge without preliminary skin testing in adult patients with allergy and at low risk with reported penicillin allergy. Allergy Asthma Proc. 2019 Jan 1;40(1):57-61. doi: 10.2500/aap.2019.40.4184.

  PMID: 30582497 RESULT

• Graham F, Tsabouri S, Caubet JC. Hypersensitivity reactions to beta-lactams in children. Curr Opin Allergy Clin Immunol. 2018 Aug;18(4):284-290. doi: 10.1097/ACI.0000000000000453.

  PMID: 29870460 RESULT

• Mustafa SS, Conn K, Ramsey A. Comparing Direct Challenge to Penicillin Skin Testing for the Outpatient Evaluation of Penicillin Allergy: A Randomized Controlled Trial. J Allergy Clin Immunol Pract. 2019 Sep-Oct;7(7):2163-2170. doi: 10.1016/j.jaip.2019.05.037. Epub 2019 Jun 4.

  PMID: 31170542 RESULT

• Moral L, Caubet JC. Oral challenge without skin tests in children with non-severe beta-lactam hypersensitivity: Time to change the paradigm? Pediatr Allergy Immunol. 2017 Dec;28(8):724-727. doi: 10.1111/pai.12800. Epub 2017 Oct 3.

  PMID: 28892222 RESULT

• Kelso JM. Provocation Challenges to Evaluate Amoxicillin Allergy in Children. JAMA Pediatr. 2016 Jun 6;170(6):e160282. doi: 10.1001/jamapediatrics.2016.0282. Epub 2016 Jun 6. No abstract available.

  PMID: 27043299 RESULT

• Mill C, Primeau MN, Medoff E, Lejtenyi C, O'Keefe A, Netchiporouk E, Dery A, Ben-Shoshan M. Assessing the Diagnostic Properties of a Graded Oral Provocation Challenge for the Diagnosis of Immediate and Nonimmediate Reactions to Amoxicillin in Children. JAMA Pediatr. 2016 Jun 6;170(6):e160033. doi: 10.1001/jamapediatrics.2016.0033. Epub 2016 Jun 6.

  PMID: 27043788 RESULT

• Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, Brown SG, Camargo CA Jr, Cydulka R, Galli SJ, Gidudu J, Gruchalla RS, Harlor AD Jr, Hepner DL, Lewis LM, Lieberman PL, Metcalfe DD, O'Connor R, Muraro A, Rudman A, Schmitt C, Scherrer D, Simons FE, Thomas S, Wood JP, Decker WW. Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006 Feb;117(2):391-7. doi: 10.1016/j.jaci.2005.12.1303.

  PMID: 16461139 RESULT

• Lieberman P, Nicklas RA, Randolph C, Oppenheimer J, Bernstein D, Bernstein J, Ellis A, Golden DB, Greenberger P, Kemp S, Khan D, Ledford D, Lieberman J, Metcalfe D, Nowak-Wegrzyn A, Sicherer S, Wallace D, Blessing-Moore J, Lang D, Portnoy JM, Schuller D, Spector S, Tilles SA. Anaphylaxis--a practice parameter update 2015. Ann Allergy Asthma Immunol. 2015 Nov;115(5):341-84. doi: 10.1016/j.anai.2015.07.019. No abstract available.

  PMID: 26505932 RESULT

• Bauer ME, MacBrayne C, Stein A, Searns J, Hicks A, Sarin T, Lin T, Duffey H, Rannie M, Wickstrom K, Yang C, Bajaj L, Carel K. A Multidisciplinary Quality Improvement Initiative to Facilitate Penicillin Allergy Delabeling Among Hospitalized Pediatric Patients. Hosp Pediatr. 2021 May;11(5):427-434. doi: 10.1542/hpeds.2020-001636. Epub 2021 Apr 13.

  PMID: 33849960 RESULT

MeSH Terms

Interventions

Electronic Health Records

Intervention Hierarchy (Ancestors)

Medical Records Systems, Computerized; Medical Records; Records; Data Collection; Epidemiologic Methods; Investigative Techniques; Organization and Administration; Health Services Administration; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Results Point of Contact

• Title: Dr. Ankita Desai
• Organization: University Hospitals Cleveland Medical Center

Ankita.Desai@UHhospitals.org

216-844-3645

Study Officials

• Ankita Desai, MD

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Director of Pediatric Antimicrobial Stewardship

Model Details: Patients will be screened by questionnaire to determine No risk, Low risk, or High Risk for penicillin allergic reaction. Those that are deemed Low Risk based on questionnaire, will be subsequently challenged with graded oral amoxicillin challenge.

Study Record Dates

• First Submitted: August 18, 2021
• First Posted: August 25, 2021
• Study Start: September 22, 2021
• Primary Completion: March 30, 2022
• Study Completion: March 30, 2022
• Last Updated: July 20, 2023
• Results First Posted: July 20, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)