Amoxicillin Challenge for Penicillin Allergy Diagnosis

NCT03757052 | Unknown

• 1 other identifier: 2019-4379
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

False diagnosis of penicillin allergy are frequently reported, and have been proven detrimental to patients. Current guidelines for the assessment of drug allergies recommend that penicillin allergy be evaluated first with prick and intradermal skin tests, and then completed with a graded oral challenge, spread over at least two doses. However, it has been shown that these skin tests, in addition to consuming resources and time, are of limited, or even doubtful validity, given the poor predictive values that have been reported in the modern penicillins era. It now seems unreasonable to continue their use without addressing other, more efficient diagnostic stategies. Several groups have now demonstrated the safety, validity, and efficiency of a direct, two-step amoxicillin oral challenge (starting with 10% of the standard therapeutic dose, followed by 90 % of the dose), without prior skin tests, first for any type of reaction in the pediatric population, then for any non-immediate reaction in the adult population. The objective of this study is to demonstrate the safety, efficiency, and validity of direct, two-step graded oral challenge with amoxicillin for the evaluation of any reported penicillin allergy in the adult population, excluding high-risk patients (documented anaphylaxis to a penicillin in the last 5 years). Skin tests will first be performed according to the protocol currently in use at the CHUL, then consented patients will proceed with the graded oral challenge still according to the protocol currently in use at the CHUL, but regardless of the skin tests results. The results of the two tests will be compared to determine the safety, efficiency and validity of proceeding directly to the graded oral challenge.

Conditions

Penicillin Allergy

Outcome Measures

Primary Outcomes (1)

• Type 1 Hypersensitivity Reaction

  The primary outcome is the occurrence of immediate hypersensitivity symptoms, occuring during the test period, which is up to 60 minutes after the last dose of amoxicillin.

  60 minutes

Secondary Outcomes (3)

• Skin Tests Results

  60 minutes

• Severity of immediate hypersensitivity symptoms

  60 minutes

• Delayed hypersensitivity symptoms

  14 days

Study Arms (1)

Skin testing and Graded Oral Challenge

EXPERIMENTAL

Penicillin skin testing as described in the intervention section, followed by amoxicillin graded oral challenge as described in the intervention section

Diagnostic Test: Penicillin Skin Testing

Interventions

Penicillin Skin Testing DIAGNOSTIC_TEST

Skin test protocol: prick skin tests (penicilloyl-polylysine 0.000012 mol/0.05 mL, penicillin G 10,000 U/mL, penoate 10,000 U/mL, ampicillin 100 mg/mL, amoxicillin 71 mg/mL, histamine/positive control, diluent/negative control), then intradermal skin tests (penicilloyl-polylysine 0.000012 mol/0.05 mL, penicillin G 10,000 U/mL, penoate 10,000 U/mL, ampicillin 1 mg/mL, diluent/negative control), administered as an intradermal injection of a standardized volume of 0.02 mL. Graded oral challenge with amoxicillin : a first dose of 50 mg of amoxicillin; 20-minute observation period; in the absence of any objective symptom of an allergic reaction, a second dose of amoxicillin of 450 mg; final observation period of 60 minutes, under nurse and medical supervision.

Also known as: Amoxicillin Graded Oral Challenge

Skin testing and Graded Oral Challenge

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Being 18 years of age or older at the time of the test
• Being referred by a health professional for the evaluation of any allergic reaction to a penicillin, including natural penicillins, anti-staphylococcal penicillins, aminopenicillins, penicillins combined with a beta-lactamase inhibitor, and carboxypenicillins ; or an antibiotic of the beta-lactam family, whose assessment requires testing for penicillins, according to the treating allergist

You may not qualify if:

• Pregnancy
• Poorly controlled asthma, chronic lung disease or heart disease
• Failure to stop beta-blockers prior to the test
• Occurrence of the reaction in the 4 weeks preceding the test (possibility of false negatives)
• History of severe delayed hypersensitivity reaction, reaction requiring hospitalization of more than 24 hours, or bullous, pustular, exfoliative or mucosal reaction (excluding angioedema)
• Recent anaphylaxis (\<5 years), defined as concomitant involvement of at least two systems (respiratory, digestive, mucocutaneous or cardiovascular) within one hour of administration of the drug

Sponsors & Collaborators

• CHU de Quebec-Universite Laval: lead

Study Sites (1)

CHU de Quebec

Québec, Quebec, Canada

RECRUITING

Study Officials

• Jean-Philippe Drolet, MD FRCPC

  CHU de Quebec-Universite Laval

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jean-Philippe Drolet, MD FRCPC

CONTACT

418-525-4444; jean-philippe.drolet@chudequebec.ca

Gaston De Serres, MD PhD

CONTACT

418-525-4444; Gaston.DeSerres@inspq.qc.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2018
• First Posted: November 28, 2018
• Study Start: November 20, 2018
• Primary Completion: April 1, 2020
• Study Completion: June 1, 2020
• Last Updated: March 14, 2019

Record last verified: 2019-03

Locations

CA (1)