Penicillin Allergy Delabeling After a One-Dose Versus Two-Dose Graded Direct Oral Challenge

NCT06303128 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: IRB-FY2024-61
• Study Type: interventional
• Target: 380
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn about dosing when testing to see if a penicillin allergy label can be removed from adults that had been labeled as "penicillin-allergic" previously. The main question it aims to answer is: \- In penicillin-allergic patients that are at low risk of having an allergic reaction, is a one-dose oral challenge with amoxicillin (a penicillin-based antibiotic) as safe and effective as a two-dose oral challenge? Participants will, after being identified as having a low-risk penicillin allergy, be administered oral amoxicillin in a controlled setting and then monitored for an allergic reaction. Researchers will compare participants that took one dose of amoxicillin to participants that took two doses of amoxicillin (a small dose and then a larger dose) to see if either group was more likely to develop an allergic reaction.

Conditions

Penicillin Allergy

Keywords

low-risk allergy; amoxicillin; drug allergy; direct oral challenge

Outcome Measures

Primary Outcomes (1)

• Proportion of successfully "delabeled" subjects in one-dose versus two-dose groups

  Percentage of subjects that successfully complete either the one-dose or graded two-dose direct oral challenge with amoxicillin without adverse reactions during the challenge, as determined by no reaction reported at first follow up phone call.

  5 days (at time of first follow up phone call)

Secondary Outcomes (4)

• Analysis of adverse reactions

  2 hours (during direct oral challenge) and 5 days (at time of first follow up phone call)

• Analysis of medical and allergic history

  Reported at time of direct oral challenge

• Validation of penicillin allergy delabeling

  6 months

• Analysis of demographic data

  Reported at time of direct oral challenge

Study Arms (2)

One-dose group

EXPERIMENTAL

Patients assigned to this group will receive a liquid placebo followed by full-dose liquid amoxicillin 250mg PO thirty minutes later.

Drug: Amoxicillin 250 MG; Drug: Placebo

Graded, two-dose group

ACTIVE COMPARATOR

Patients assigned to this group will receive liquid amoxicillin (25% of 250mg dose), followed by liquid amoxicillin 187.5mg PO (75% of 250mg dose) thirty minutes later.

Drug: Amoxicillin 62.5mg; Drug: Amoxicillin 187.5mg

Interventions

Amoxicillin 250 MG DRUG

Liquid amoxicillin 250mg PO

Also known as: One-dose group

One-dose group

Placebo DRUG

Given prior to amoxicillin 250mg in one-dose group

Also known as: Liquid placebo (Syrpalta or similar) for one-dose group

One-dose group

Amoxicillin 62.5mg DRUG

Given first in two-dose group, liquid amoxicillin 62.5mg PO

Also known as: Two-dose group, dose 1 of 2

Graded, two-dose group

Amoxicillin 187.5mg DRUG

Given second in two-dose group, liquid amoxicillin 187.5mg PO

Also known as: Two-dose group, dose 2 of 2

Graded, two-dose group

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Expresses interest in participating by calling or filling out information form on study website
• Reports an allergy to one of the following medications: penicillin VK, penicillin G, amoxicillin, ampicillin, dicloxacillin, flucloxacillin, nafcillin, oxacillin, amoxicillin- clavulanate, ampicillin-sulbactam. Subjects with an unspecified penicillin allergy are also eligible to participate.

You may not qualify if:

• Penicillin allergy deemed to be more than "low-risk" per PEN-FAST (score ≥ 3 points)
• History of acute kidney injury (acute interstitial nephritis), severe liver impairment (drug- induced liver injury), serum sickness, or isolated drug fever attributed to a penicillin- based antibiotic
• Anaphylaxis for any reason in the last year
• Cognitive impairment where a collateral history could not be obtained and/or patient does not have capacity to consent for themselves
• Pregnant (self-reported)
• Any illness or condition that would increase the risk of participation in the study, per the evaluating clinician's judgment
• Active treatment of or history of acute angle closure glaucoma
• On H1- or H2-blockers (i.e. diphenhydramine, hydroxyzine, chlorpheniramine, cetirizine, levocetirizine, loratadine, fexofenadine or famotidine, ranitidine, cimetidine, nizatidine, respectively) within 72 hours of initiating direct oral challenge (will be counseled to discontinue prior to testing)
• Actively receiving greater than stress dose steroid (hydrocortisone \>50mg four times a day or steroid equivalent)
• Actively receiving any antibiotic
• Relative contraindication: Patients on beta blockers and angiotensin converting enzyme inhibitors (ACE inhibitors) will have an open dialog with the study team regarding the risks and benefits of testing a low-risk penicillin allergy patient. A joint decision will be made based on the patient's preference and the physician's comfort level.

Sponsors & Collaborators

• James Tarbox, MD: lead
• Texas Tech University Health Sciences Center: collaborator

Study Sites (1)

Texas Tech University Health Sciences Center

Lubbock, Texas, 79430, United States

RECRUITING

Related Publications (14)

• Blumenthal KG, Peter JG, Trubiano JA, Phillips EJ. Antibiotic allergy. Lancet. 2019 Jan 12;393(10167):183-198. doi: 10.1016/S0140-6736(18)32218-9. Epub 2018 Dec 14.

  PMID: 30558872 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

• Khan DA, Banerji A, Blumenthal KG, Phillips EJ, Solensky R, White AA, Bernstein JA, Chu DK, Ellis AK, Golden DBK, Greenhawt MJ, Horner CC, Ledford D, Lieberman JA, Oppenheimer J, Rank MA, Shaker MS, Stukus DR, Wallace D, Wang J; Chief Editor(s):; Khan DA, Golden DBK, Shaker M, Stukus DR; Workgroup Contributors:; Khan DA, Banerji A, Blumenthal KG, Phillips EJ, Solensky R, White AA; Joint Task Force on Practice Parameters Reviewers:; Bernstein JA, Chu DK, Ellis AK, Golden DBK, Greenhawt MJ, Horner CC, Ledford D, Lieberman JA, Oppenheimer J, Rank MA, Shaker MS, Stukus DR, Wallace D, Wang J. Drug allergy: A 2022 practice parameter update. J Allergy Clin Immunol. 2022 Dec;150(6):1333-1393. doi: 10.1016/j.jaci.2022.08.028. Epub 2022 Sep 17. No abstract available.

  PMID: 36122788 BACKGROUND

• Iammatteo M, Lezmi G, Confino-Cohen R, Tucker M, Ben-Shoshan M, Caubet JC. Direct Challenges for the Evaluation of Beta-Lactam Allergy: Evidence and Conditions for Not Performing Skin Testing. J Allergy Clin Immunol Pract. 2021 Aug;9(8):2947-2956. doi: 10.1016/j.jaip.2021.04.073.

  PMID: 34366093 BACKGROUND

• Iammatteo M, Alvarez Arango S, Ferastraoaru D, Akbar N, Lee AY, Cohen HW, Jerschow E. Safety and Outcomes of Oral Graded Challenges to Amoxicillin without Prior Skin Testing. J Allergy Clin Immunol Pract. 2019 Jan;7(1):236-243. doi: 10.1016/j.jaip.2018.05.008. Epub 2018 May 23.

  PMID: 29802906 BACKGROUND

• Copaescu AM, Vogrin S, James F, Chua KYL, Rose MT, De Luca J, Waldron J, Awad A, Godsell J, Mitri E, Lambros B, Douglas A, Youcef Khoudja R, Isabwe GAC, Genest G, Fein M, Radojicic C, Collier A, Lugar P, Stone C, Ben-Shoshan M, Turner NA, Holmes NE, Phillips EJ, Trubiano JA. Efficacy of a Clinical Decision Rule to Enable Direct Oral Challenge in Patients With Low-Risk Penicillin Allergy: The PALACE Randomized Clinical Trial. JAMA Intern Med. 2023 Sep 1;183(9):944-952. doi: 10.1001/jamainternmed.2023.2986.

  PMID: 37459086 BACKGROUND

• Wang LA, Patel K, Kuruvilla ME, Shih J. Direct amoxicillin challenge without preliminary skin testing for pediatric patients with penicillin allergy labels. Ann Allergy Asthma Immunol. 2020 Aug;125(2):226-228. doi: 10.1016/j.anai.2020.05.004. Epub 2020 May 11. No abstract available.

  PMID: 32407949 BACKGROUND

• Lin L, Nagtegaal JE, Buijtels PCAM, Jong E. Antimicrobial stewardship intervention: optimizing antibiotic treatment in hospitalized patients with reported antibiotic allergy. J Hosp Infect. 2020 Feb;104(2):137-143. doi: 10.1016/j.jhin.2019.10.007. Epub 2019 Oct 13.

  PMID: 31618608 BACKGROUND

• Trubiano JA, Smibert O, Douglas A, Devchand M, Lambros B, Holmes NE, Chua KY, Phillips EJ, Slavin MA. The Safety and Efficacy of an Oral Penicillin Challenge Program in Cancer Patients: A Multicenter Pilot Study. Open Forum Infect Dis. 2018 Nov 17;5(12):ofy306. doi: 10.1093/ofid/ofy306. eCollection 2018 Dec.

  PMID: 30547046 BACKGROUND

• Chua KYL, Vogrin S, Bury S, Douglas A, Holmes NE, Tan N, Brusco NK, Hall R, Lambros B, Lean J, Stevenson W, Devchand M, Garrett K, Thursky K, Grayson ML, Slavin MA, Phillips EJ, Trubiano JA. The Penicillin Allergy Delabeling Program: A Multicenter Whole-of-Hospital Health Services Intervention and Comparative Effectiveness Study. Clin Infect Dis. 2021 Aug 2;73(3):487-496. doi: 10.1093/cid/ciaa653.

  PMID: 32756983 BACKGROUND

• Tucker MH, Lomas CM, Ramchandar N, Waldram JD. Amoxicillin challenge without penicillin skin testing in evaluation of penicillin allergy in a cohort of Marine recruits. J Allergy Clin Immunol Pract. 2017 May-Jun;5(3):813-815. doi: 10.1016/j.jaip.2017.01.023. Epub 2017 Mar 21. No abstract available.

  PMID: 28341170 BACKGROUND

• 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 BACKGROUND

• Chow TG, Patel G, Mohammed M, Johnson D, Khan DA. Delabeling penicillin allergy in a pediatric primary care clinic. Ann Allergy Asthma Immunol. 2023 May;130(5):667-669. doi: 10.1016/j.anai.2023.01.034. Epub 2023 Feb 2. No abstract available.

  PMID: 36738783 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

Related Links

• Recruiting Website

MeSH Terms

Conditions

Drug Hypersensitivity

Interventions

Amoxicillin; Population Groups; WW Domain-Containing Oxidoreductase

Condition Hierarchy (Ancestors)

Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders

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; Demography; Population Characteristics; Short Chain Dehydrogenase-Reductases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Tumor Suppressor Proteins; Neoplasm Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• James A Tarbox, MD

  Texas Tech University Health Sciences Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Coordinator

CONTACT

806-543-8994; clinicalresearch@ttuhsc.edu

Joshua A Peterson, MD

CONTACT

josh.peterson.587@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: \- Low-risk penicillin allergic patients ("low-risk" determined by a PEN-FAST score of 2 or less) will be recruited. Clinically stable patients will be randomly assigned in a double-blinded manner to receive either a one-dose or graded two-dose direct oral challenge with amoxicillin in an outpatient setting. Those assigned to receive one dose of amoxicillin will receive a placebo in place of a second dose of amoxicillin. Both groups will receive the same cumulative dose of amoxicillin (250mg) by the end of the trial. Baseline vital signs will be obtained and tracked throughout the trial. Patients will also be monitored for development of signs of allergic reactions during the trial, with administration of appropriate treatment should the need arise.

Study Record Dates

• First Submitted: March 4, 2024
• First Posted: March 12, 2024
• Study Start: February 3, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 1, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: Researchers who provide a methodologically sound proposal to achieve aims in the approved proposal.

Locations

US (1)